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Sample records for glomerular barrier permselectivity

  1. Losartan therapy decreases albuminuria with stable glomerular filtration and permselectivity in sickle cell anemia.

    Science.gov (United States)

    Yee, Marianne E; Lane, Peter A; Archer, David R; Joiner, Clinton H; Eckman, James R; Guasch, Antonio

    2018-03-01

    Sickle cell nephropathy begins with hyperfiltration and microalbuminuria and may progress to renal failure. The aim of this study was to determine the effects of losartan on glomerular function and albumin excretion in sickle cell anemia (SCA). Individuals with SCA on hydroxyurea with persistent albuminuria were enrolled in a 1-year study of losartan. Glomerular filtration rate (GFR) measured by iohexol clearance, albumin excretion rate (AER), and fractional clearance of dextran were assessed at baseline, short-term (1-2month), and long-term (≥12month) intervals. Twelve subjects (6 microalbuminuria, 6 macroalbuminuria) completed short-term studies; 8 completed long-term studies. Baseline GFR was 112ml/min/1.73m 2 (71-147ml/min/1.73m 2 ). AER decreased significantly at the short-term (median decrease -134 mcg/min, p=0.0063). GFR was not significantly-different at short-term or long-term intervals. Dextran clearance improved for diameters smaller than albumin (therapy for ≥1year in sickle nephropathy results in lower albumin excretion with stable GFR. Filtration of neutral molecules ≥36Å was not changed by losartan, suggesting that the effect of losartan is a mechanism other than alteration of glomerular filtration size-selectivity. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Update on the glomerular filtration barrier.

    Science.gov (United States)

    Jarad, George; Miner, Jeffrey H

    2009-05-01

    The nephrology community lacks a unified view of protein sieving through the glomerular capillary wall. The glomerular capillary wall consists of three distinct but closely interacting layers: the fenestrated endothelium, with its glycocalyx; the podocytes, with their interdigitated foot processes and slit diaphragms; and the intervening glomerular basement membrane. Proteinuria is associated with abnormalities in any one layer, suggesting that each contributes to the glomerular filtration barrier (GFB). Proteinuria can also be induced in the context of a normal glomerular capillary wall. Here, we review some classic studies as well as some newer concepts and present competing hypotheses about the GFB. Two almost forgotten concepts have recently emerged. One group has challenged the exquisite selectivity of the GFB to albumin and suggested that proteinuria is the result of abnormal tubular uptake. There has also been a reemphasis on diffusion through the glomerular basement membrane as the driving force behind macromolecular filtration. New evidence suggests that the endothelial glycocalyx is an important charge-selective barrier. We suggest viewing the GFB as a dynamic rather than as a rigid barrier, requiring three healthy layers and a hemodynamic steady state. Multiple challenges to studying the endothelium, the tubular handling of albumin, and the role of hemodynamic forces will require new tools, new hypotheses, and open minds.

  3. Molecular make-up of the glomerular filtration barrier.

    Science.gov (United States)

    Patrakka, Jaakko; Tryggvason, Karl

    2010-05-21

    The glomerular filtration barrier is composed of glomerular endothelial cells, the glomerulus basement membrane and the podocyte cell layer. The filtration barrier is a target of injury in several systemic and renal diseases, and this often leads to progressive renal disease and kidney failure. Therefore, it is essential to understand the molecular biology of the glomerulus. During the last two decades, a lot of new information about molecular components of the glomerulus filtration barrier has been generated. Many of the key discoveries have been obtained through studies on the genetic background of inherited glomerular diseases. These studies have emphasized the role of podocytes in the filtration barrier function. During the last decade, the use of knockout mouse technology has become more available and given important new insights into the functional significance of glomerular components. Large-scale approaches, such as microarray profiling, have also given data about molecules involved in the biology and pathology of the glomerulus. In the coming decade, the use of global expression profiling platforms, transgenic mouse lines, and other in vivo gene delivery methods will rapidly expand our understanding of biology and pathology of the glomerular filtration barrier, and hopefully expose novel target molecules for therapy in progressive renal diseases. 2010 Elsevier Inc. All rights reserved.

  4. Glomerular basement membrane composition and the filtration barrier.

    Science.gov (United States)

    Miner, Jeffrey H

    2011-09-01

    The glomerular basement membrane (GBM) is an especially thick basement membrane that contributes importantly to the kidney's filtration barrier. The GBM derives from the fusion of separate podocyte and endothelial cell basement membranes during glomerulogenesis and consists primarily of laminin-521 (α5β2γ1), collagen α3α4α5(IV), nidogens-1 and -2, and agrin. Of these nine proteins, mutations in the genes encoding four of them (LAMB2, COL4A3, COL4A4, and COL4A5) cause glomerular disease in humans as well as in mice. Furthermore, mutation of a fifth (Lama5) gene in podocytes in mice causes proteinuria, nephrotic syndrome, and progression to renal failure. These results highlight the importance of the GBM for establishing and maintaining a properly functioning glomerular filtration barrier.

  5. Impairment in glomerular filtration rate or glomerular filtration barrier and occurrence of stroke.

    Science.gov (United States)

    Ovbiagele, Bruce

    2008-07-01

    Chronic kidney disease (CKD) is associated with substantial burden and is a strong risk factor for cardiovascular disease. However, data on the relationship between CKD and stroke are few and are limited by unreliable or inadequate assessment of renal function. To properly assess the relationship between renal insufficiency and stroke in stroke survivors in the United States by simultaneously examining the effect of guideline-recommended indices of renal disease that measure glomerular filtration rate (creatinine clearance) and glomerular filtration barrier (proteinuria). Cross sectional. Nationally representative survey of the United States. Participants aged 55 or older who participated in the National Health and Nutrition Examination Survey from 1999 to 2004. Indices of renal disease that measure glomerular filtration rate (creatinine clearance) and glomerular filtration barrier (microalbuminuria). Of 6382 adults who met inclusion criteria, 5624 (88%) had full and complete data, of which 414 (6%) reported having had a stroke. Stroke survivors were older and more likely to have CKD, diabetes, hypertension, coronary artery disease, elevated blood pressure, increased glycohemoglobin concentration, and lower hematocrit compared with respondents who did not report stroke. Multivariate models showed that microalbuminuria (odds ratio, 1.51; 95% confidence interval, 1.02-2.24), decreased glomerular filtration rate (odds ratio, 1.93; 95% confidence interval, 1.28-2.91), and stage 3 CKD (odds ratio, 2.09; 95% confidence interval, 1.38-3.16) were significantly associated with stroke. Stroke is independently associated with impairment in structure and function of the glomerulus, which supports the need to consider screening patients with stroke for CKD and to simultaneously assess for both indices of renal disease.

  6. Glomerular endothelial surface layer acts as a barrier against albumin filtration

    NARCIS (Netherlands)

    Dane, M.J.; Berg, B.M. van den; Avramut, M.C.; Faas, F.G.; Vlag, J. van der; Rops, A.L.; Ravelli, R.B.; Koster, B.J.; Zonneveld, A.J. van; Vink, H.; Rabelink, T.J.

    2013-01-01

    Glomerular endothelium is highly fenestrated, and its contribution to glomerular barrier function is the subject of debate. In recent years, a polysaccharide-rich endothelial surface layer (ESL) has been postulated to act as a filtration barrier for large molecules, such as albumin. To test this

  7. Glomerular endothelial surface layer acts as a barrier against albumin filtration.

    Science.gov (United States)

    Dane, Martijn J C; van den Berg, Bernard M; Avramut, M Cristina; Faas, Frank G A; van der Vlag, Johan; Rops, Angelique L W M M; Ravelli, Raimond B G; Koster, Bram J; van Zonneveld, Anton Jan; Vink, Hans; Rabelink, Ton J

    2013-05-01

    Glomerular endothelium is highly fenestrated, and its contribution to glomerular barrier function is the subject of debate. In recent years, a polysaccharide-rich endothelial surface layer (ESL) has been postulated to act as a filtration barrier for large molecules, such as albumin. To test this hypothesis, we disturbed the ESL in C57Bl/6 mice using long-term hyaluronidase infusion for 4 weeks and monitored albumin passage using immunolabeling and correlative light-electron microscopy that allows for complete and integral assessment of glomerular albumin passage. ESL ultrastructure was visualized by transmission electron microscopy using cupromeronic blue and by localization of ESL binding lectins using confocal microscopy. We demonstrate that glomerular fenestrae are filled with dense negatively charged polysaccharide structures that are largely removed in the presence of circulating hyaluronidase, leaving the polysaccharide surfaces of other glomerular cells intact. Both retention of native ferritin [corrected] in the glomerular basement membrane and systemic blood pressure were unaltered. Enzyme treatment, however, induced albumin passage across the endothelium in 90% of glomeruli, whereas this could not be observed in controls. Yet, there was no net albuminuria due to binding and uptake of filtered albumin by the podocytes and parietal epithelium. ESL structure and function completely recovered within 4 weeks on cessation of hyaluronidase infusion. Thus, the polyanionic ESL component, hyaluronan, is a key component of the glomerular endothelial protein permeability barrier. Copyright © 2013 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  8. Podocyte-specific overexpression of metallothionein mitigates diabetic complications in the glomerular filtration barrier and glomerular histoarchitecture: a transmission electron microscopy stereometric analysis.

    Science.gov (United States)

    Carlson, Edward C; Chhoun, Jennifer M; Laturnus, Donna I; Bikash, K C; Berg, Brittany; Zheng, Shirong; Epstein, Paul N

    2013-02-01

    We previously demonstrated that cellular and extracellular components of the blood-urine barrier in renal glomeruli are susceptible to damage in OVE transgenic mice, a valuable model of human diabetic nephropathy that expresses profound albuminuria. To test our hypothesis that glomerular filtration barrier damage in OVE mice may be the result of oxidative insult to podocytes, 150-day-old bi-transgenic OVENmt diabetic mice that overexpress the antioxidant metallothionein specifically in podocytes were examined by enzyme-linked immunosorbent assay for albuminuria mitigation and by unbiased transmission electron microscopy (TEM) stereometry for protection from chronic structural diabetic complications. Although blood glucose and HbA(1c) levels were indistinguishable in OVE and OVENmt animals, albuminuria was significantly reduced (average >7-fold) in OVENmt mice through 8 months of age. Interestingly, the Nmt transgene provided significant glomerular protection against diabetic nephropathic complications outside of the podocyte. Glomerular filtration barrier damage was reduced in OVENmt mice, including significantly increased area occupied by endothelial luminal fenestrations (~13%), significantly reduced glomerular basement membrane (GBM) thickening (~17%) and significantly less podocyte effacement (~18%). In addition, OVENmt mice exhibited significantly reduced glomerular volume (~50%), fewer glomerular endothelial cells (~33%), fewer mesangial cells (~57%) and fewer total glomerular cells (~40%). These results provide evidence of oxidative damage to podocytes induces primary diabetic nephropathic features including severe and sustained albuminuria, specific glomerular filtration barrier damage and alterations in glomerular endothelial and mesangial cell number. Importantly, these diabetic complications are significantly mitigated by podocyte targeted metallothionein overexpression. Copyright © 2012 John Wiley & Sons, Ltd.

  9. Resolution of the three dimensional structure of components of the glomerular filtration barrier

    DEFF Research Database (Denmark)

    Arkill, Kenton P; Qvortrup, Klaus; Starborg, Tobias

    2014-01-01

    The human glomerulus is the primary filtration unit of the kidney, and contains the Glomerular Filtration Barrier (GFB). The GFB had been thought to comprise 3 layers - the endothelium, the basement membrane and the podocyte foot processes. However, recent studies have suggested that at least two...

  10. Sieve plugs in fenestrae of glomerular capillaries--site of the filtration barrier?

    DEFF Research Database (Denmark)

    Rostgaard, Jørgen; Qvortrup, Klaus

    2002-01-01

    The exact location of the filtration barrier of the glomerular capillary wall, which consists of an endothelium, a basement membrane and a visceral epithelium, has not yet been determined. Apparent discrepancies between different investigators in the past could be explained if postmortem artifact...

  11. Sieve plugs in fenestrae of glomerular capillaries--site of the filtration barrier?

    DEFF Research Database (Denmark)

    Rostgaard, Jørgen; Qvortrup, Klaus

    2002-01-01

    perfusion pressure and a fixative composed of an oxygen-carrying blood substitute fluid containing glutaraldehyde, was employed combined with contrast enhancement. New observations of the glomerular capillary wall revealed that filamentous plugs (about 90 nm in height) filled the capillary fenestrae......The exact location of the filtration barrier of the glomerular capillary wall, which consists of an endothelium, a basement membrane and a visceral epithelium, has not yet been determined. Apparent discrepancies between different investigators in the past could be explained if postmortem...... artifactual tissue changes, due to subnormal blood pressure or anoxia, have taken place in the endothelium before the tissue and tracers have been sufficiently fixed and immobilized by the fixative. To test this supposition, a new method of fixation, which includes a technique to maintain a physiological...

  12. The adaptor protein Grb2 is not essential for the establishment of the glomerular filtration barrier.

    Directory of Open Access Journals (Sweden)

    Nicolas Bisson

    Full Text Available The kidney filtration barrier is formed by the combination of endothelial cells, basement membrane and epithelial cells called podocytes. These specialized actin-rich cells form long and dynamic protrusions, the foot processes, which surround glomerular capillaries and are connected by specialized intercellular junctions, the slit diaphragms. Failure to maintain the filtration barrier leads to massive proteinuria and nephrosis. A number of proteins reside in the slit diaphragm, notably the transmembrane proteins Nephrin and Neph1, which are both able to act as tyrosine phosphorylated scaffolds that recruit cytoplasmic effectors to initiate downstream signaling. While association between tyrosine-phosphorylated Neph1 and the SH2/SH3 adaptor Grb2 was shown in vitro to be sufficient to induce actin polymerization, in vivo evidence supporting this finding is still lacking. To test this hypothesis, we generated two independent mouse lines bearing a podocyte-specific constitutive inactivation of the Grb2 locus. Surprisingly, we show that mice lacking Grb2 in podocytes display normal renal ultra-structure and function, thus demonstrating that Grb2 is not required for the establishment of the glomerular filtration barrier in vivo. Moreover, our data indicate that Grb2 is not required to restore podocyte function following kidney injury. Therefore, although in vitro experiments suggested that Grb2 is important for the regulation of actin dynamics, our data clearly shows that its function is not essential in podocytes in vivo, thus suggesting that Grb2 rather plays a secondary role in this process.

  13. Glomerular barrier behaves as an atomically precise bandpass filter in a sub-nanometre regime

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    Du, Bujie; Jiang, Xingya; Das, Anindita; Zhou, Qinhan; Yu, Mengxiao; Jin, Rongchao; Zheng, Jie

    2017-11-01

    The glomerular filtration barrier is known as a 'size cutoff' slit, which retains nanoparticles or proteins larger than 6-8 nm in the body and rapidly excretes smaller ones through the kidneys. However, in the sub-nanometre size regime, we have found that this barrier behaves as an atomically precise 'bandpass' filter to significantly slow down renal clearance of few-atom gold nanoclusters (AuNCs) with the same surface ligands but different sizes (Au18, Au15 and Au10-11). Compared to Au25 (∼1.0 nm), just few-atom decreases in size result in four- to ninefold reductions in renal clearance efficiency in the early elimination stage, because the smaller AuNCs are more readily trapped by the glomerular glycocalyx than larger ones. This unique in vivo nano-bio interaction in the sub-nanometre regime also slows down the extravasation of sub-nanometre AuNCs from normal blood vessels and enhances their passive targeting to cancerous tissues through an enhanced permeability and retention effect. This discovery highlights the size precision in the body's response to nanoparticles and opens a new pathway to develop nanomedicines for many diseases associated with glycocalyx dysfunction.

  14. Effect of arctiin on glomerular filtration barrier damage in STZ-induced diabetic nephropathy rats.

    Science.gov (United States)

    Ma, Song-Tao; Liu, Dong-lian; Deng, Jing-jing; Niu, Rui; Liu, Rui-bin

    2013-10-01

    Diabetic nephropathy (DN) is the major life-threatening complication of diabetes. Abnormal permeability of glomerular basement membrane plays an important role in DN pathogenesis. This study was performed to assess the effect of arctiin, the lignan constituent from Arctium lappa L., on metabolic profile and aggravation of renal lesions in a rat model of streptozotocin (STZ)-induced DN. STZ-induced diabetic rats were treated with arctiin at the dosage of 60 or 40 mg/kg/day via intraperitoneal injection for 8 weeks. Blood glucose and 24-h urinary albumin content were measured, and kidney histopathological changes were monitored. RT-PCR and immunohistochemistry were used to detect the mRNA and protein levels of nephrin, podocin and heparanase (HPSE) in the kidney cortex of rats, respectively. Treatment with arctiin significantly decreased the levels of 24-h urinary albumin, prevented the sclerosis of glomeruli and effectively restored the glomerular filtration barrier damage by up-regulating the expression of nephrin and podocin and down-regulating HPSE level. Our studies suggest that arctiin might be beneficial for DN. The effects of arctiin on attenuating albuminuria and glomerulosclerosis are possibly mediated by regulating the expression of nephrin and podocin and HPSE in STZ-induced diabetic rats. Copyright © 2012 John Wiley & Sons, Ltd.

  15. Resolution of the three dimensional structure of components of the glomerular filtration barrier.

    Science.gov (United States)

    Arkill, Kenton P; Qvortrup, Klaus; Starborg, Tobias; Mantell, Judith M; Knupp, Carlo; Michel, C Charles; Harper, Steve J; Salmon, Andy H J; Squire, John M; Bates, Dave O; Neal, Chris R

    2014-02-01

    The human glomerulus is the primary filtration unit of the kidney, and contains the Glomerular Filtration Barrier (GFB). The GFB had been thought to comprise 3 layers - the endothelium, the basement membrane and the podocyte foot processes. However, recent studies have suggested that at least two additional layers contribute to the function of the GFB, the endothelial glycocalyx on the vascular side, and the sub-podocyte space on the urinary side. To investigate the structure of these additional layers is difficult as it requires three-dimensional reconstruction of delicate sub-microscopic (glomerular volume). Secondly, Focused Ion Beam milling Scanning Electron Microscopy (FIB-SEM) was used to image a filtration region (48 μm3 volume). Lastly Transmission Electron Tomography (Tom-TEM) was performed on a 0.3 μm3 volume to identify the fine structure of the glycocalyx. Tom-TEM clearly showed 20 nm fibre spacing in the glycocalyx, within a limited field of view. FIB-SEM demonstrated, in a far greater field of view, how the glycocalyx structure related to fenestrations and the filtration slits, though without the resolution of TomTEM. SBF-SEM was able to determine the extent of the sub-podocyte space and glycocalyx coverage, without additional heavy metal staining. Neither SBF- nor FIB-SEM suffered the anisotropic shrinkage under the electron beam that is seen with Tom-TEM. These images demonstrate that the three dimensional structure of the GFB can be imaged, and investigated from the whole glomerulus to the fine structure of the glycocalyx using three dimensional electron microscopy techniques. This should allow the identification of structural features regulating physiology, and their disruption in pathological states, aiding the understanding of kidney disease.

  16. Loss of mucin-type O-glycans impairs the integrity of the glomerular filtration barrier in the mouse kidney.

    Science.gov (United States)

    Song, Kai; Fu, Jianxin; Song, Jianhua; Herzog, Brett H; Bergstrom, Kirk; Kondo, Yuji; McDaniel, J Michael; McGee, Samuel; Silasi-Mansat, Robert; Lupu, Florea; Chen, Hong; Bagavant, Harini; Xia, Lijun

    2017-10-06

    The kidney's filtration activity is essential for removing toxins and waste products from the body. The vascular endothelial cells of the glomerulus are fenestrated, flattened, and surrounded by podocytes, specialized cells that support glomerular endothelial cells. Mucin-type core 1-derived O- glycans ( O -glycans) are highly expressed on both glomerular capillary endothelial cells and their supporting podocytes, but their biological role is unclear. Biosynthesis of core 1-derived O -glycans is catalyzed by the glycosyltransferase core 1 β1,3-galactosyltransferase (C1galt1). Here we report that neonatal or adult mice with inducible deletion of C1galt1 ( iC1galt1 -/- ) exhibit spontaneous proteinuria and rapidly progressing glomerulosclerosis. Ultrastructural analysis of the glomerular filtration barrier components revealed that loss of O -glycans results in altered podocyte foot processes. Further analysis indicated that O -glycan is essential for the normal signaling function of podocalyxin, a podocyte foot process-associated glycoprotein. Our results reveal a new function of O -glycosylation in the integrity of the glomerular filtration barrier. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  17. Dynamic, size-selective effects of protamine sulfate and hyaluronidase on the rat glomerular filtration barrier in vivo.

    Science.gov (United States)

    Sverrisson, Kristinn; Axelsson, Josefin; Rippe, Anna; Asgeirsson, Daniel; Rippe, Bengt

    2014-11-15

    The proteinuric actions of protamine sulfate (PS) have classically been, at least partly, attributed to alterations of the negatively charged glomerular endothelial glycocalyx. To investigate whether the charge-selective properties of the glomerular filtration barrier (GFB) would be altered by PS, we assessed the glomerular sieving of conventional, uncharged, polydispersed Ficoll (n-Ficoll) compared with charge modified, conformationally intact, anionic (carboxymethylated) Ficoll (a-Ficoll) before and after systemic infusions of PS in rats. For comparison, we also investigated the impact of hyaluronidase (hyase), which partially degrades the glycocalyx, on GFB permeability. In anaesthetized Wistar rats, blood access was achieved, and the left ureter was cannulated for urine collection. Rats were infused with either n-Ficoll or a-Ficoll before and during systemic infusions with either PS or hyase. Plasma and urine samples were taken repeatedly and analyzed by high-performance size exclusion chromatography to assess glomerular sieving coefficients (θ) for Ficoll (radius 10-80 Å). The GFB showed a significant glomerular charge selectivity for Ficoll molecules of radius 20-35 Å. PS and hyase infusions reversibly increased θ for large Ficoll molecules (Ficoll molecules of radius 50-80 Å). Thus, for PS, θ for a-Ficoll molecules of radius 70 Å increased from 2.47 × 10(-5) ± 1.1(-5) to 7.25 × 10(-5) ± 1.1(-5) (P < 0.05) at 15 min. For hyase, changes in a-Ficoll molecules of radius 50-80 Å were, however, not statistically significant. Neither PS nor hyase had any effect on θ for n-Ficoll molecules of radius 20-45 Å or a-Ficoll molecules of radius 20-45 Å. It is concluded that systemically administered PS and hyase in moderate doses dynamically decreased the size selectivity of the rat GFB without affecting its charge selective properties. Copyright © 2014 the American Physiological Society.

  18. Systemic Monocyte Chemotactic Protein-1 Inhibition Modifies Renal Macrophages and Restores Glomerular Endothelial Glycocalyx and Barrier Function in Diabetic Nephropathy.

    Science.gov (United States)

    Boels, Margien G S; Koudijs, Angela; Avramut, M Cristina; Sol, Wendy M P J; Wang, Gangqi; van Oeveren-Rietdijk, Annemarie M; van Zonneveld, Anton Jan; de Boer, Hetty C; van der Vlag, Johan; van Kooten, Cees; Eulberg, Dirk; van den Berg, Bernard M; IJpelaar, Daphne H T; Rabelink, Ton J

    2017-11-01

    Inhibition of monocyte chemotactic protein-1 (MCP-1) with the Spiegelmer emapticap pegol (NOX-E36) shows long-lasting albuminuria-reducing effects in diabetic nephropathy. MCP-1 regulates inflammatory cell recruitment and differentiation of macrophages. Because the endothelial glycocalyx is also reduced in diabetic nephropathy, we hypothesized that MCP-1 inhibition restores glomerular barrier function through influencing macrophage cathepsin L secretion, thus reducing activation of the glycocalyx-degrading enzyme heparanase. Four weeks of treatment of diabetic Apoe knockout mice with the mouse-specific NOX-E36 attenuated albuminuria without any change in systemic hemodynamics, despite persistent loss of podocyte function. MCP-1 inhibition, however, increased glomerular endothelial glycocalyx coverage, with preservation of heparan sulfate. Mechanistically, both glomerular cathepsin L and heparanase expression were reduced. MCP-1 inhibition resulted in reduced CCR2-expressing Ly6C hi monocytes in the peripheral blood, without affecting overall number of kidney macrophages at the tissue level. However, the CD206 + /Mac3 + cell ratio, as an index of presence of anti-inflammatory macrophages, increased in diabetic mice after treatment. Functional analysis of isolated renal macrophages showed increased release of IL-10, whereas tumor necrosis factor and cathepsin L release was reduced, further confirming polarization of tissue macrophages toward an anti-inflammatory phenotype during mouse-specific NOX-E36 treatment. We show that MCP-1 inhibition restores glomerular endothelial glycocalyx and barrier function and reduces tissue inflammation in the presence of ongoing diabetic injury, suggesting a therapeutic potential for NOX-E36 in diabetic nephropathy. Copyright © 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  19. The Rho-GTPase binding protein IQGAP2 is required for the glomerular filtration barrier.

    Science.gov (United States)

    Sugano, Yuya; Lindenmeyer, Maja T; Auberger, Ines; Ziegler, Urs; Segerer, Stephan; Cohen, Clemens D; Neuhauss, Stephan C F; Loffing, Johannes

    2015-11-01

    Podocyte dysfunction impairs the size selectivity of the glomerular filter, leading to proteinuria, hypoalbuminuria, and edema, clinically defined as nephrotic syndrome. Hereditary forms of nephrotic syndrome are linked to mutations in podocyte-specific genes. To identify genes contributing to podocyte dysfunction in acquired nephrotic syndrome, we studied human glomerular gene expression data sets for glomerular-enriched gene transcripts differentially regulated between pretransplant biopsy samples and biopsies from patients with nephrotic syndrome. Candidate genes were screened by in situ hybridization for expression in the zebrafish pronephros, an easy-to-use in vivo assay system to assess podocyte function. One glomerulus-enriched product was the Rho-GTPase binding protein, IQGAP2. Immunohistochemistry found a strong presence of IQGAP2 in normal human and zebrafish podocytes. In zebrafish larvae, morpholino-based knockdown of iqgap2 caused a mild foot process effacement of zebrafish podocytes and a cystic dilation of the urinary space of Bowman's capsule upon onset of urinary filtration. Moreover, the glomerulus of zebrafish morphants showed a glomerular permeability for injected high-molecular-weight dextrans, indicating an impaired size selectivity of the glomerular filter. Thus, IQGAP2 is a Rho-GTPase binding protein, highly abundant in human and zebrafish podocytes, which controls normal podocyte structure and function as evidenced in the zebrafish pronephros.

  20. Atrasentan Reduces Albuminuria by Restoring the Glomerular Endothelial Glycocalyx Barrier in Diabetic Nephropathy.

    Science.gov (United States)

    Boels, Margien G S; Avramut, M Cristina; Koudijs, Angela; Dane, Martijn J C; Lee, Dae Hyun; van der Vlag, Johan; Koster, Abraham J; van Zonneveld, Anton Jan; van Faassen, Ernst; Gröne, Hermann-Josef; van den Berg, Bernard M; Rabelink, Ton J

    2016-08-01

    Atrasentan, a selective endothelin A receptor antagonist, has been shown to reduce albuminuria in type 2 diabetes. We previously showed that the structural integrity of a glomerular endothelial glycocalyx is required to prevent albuminuria. Therefore we tested the potential of atrasentan to stabilize the endothelial glycocalyx in diabetic apolipoprotein E (apoE)-deficient mice in relation to its antialbuminuric effects. Treatment with atrasentan (7.5 mg/kg/day) for 4 weeks reduced urinary albumin-to-creatinine ratios by 26.0 ± 6.5% (P < 0.01) in apoE knockout (KO) mice with streptozotocin-induced diabetes consuming an atherogenic diet, without changes in gross glomerular morphology, systemic blood pressure, and blood glucose concentration. Endothelial cationic ferritin surface coverage, investigated using large-scale digital transmission electron microscopy, revealed that atrasentan treatment increases glycocalyx coverage in diabetic apoE KO mice from 40.7 ± 3.2% to 81.0 ± 12.5% (P < 0.05). This restoration is accompanied by increased renal nitric oxide concentrations, reduced expression of glomerular heparanase, and a marked shift in the balance of M1 and M2 glomerular macrophages. In vitro experiments with endothelial cells exposed to laminar flow and cocultured with pericytes confirmed that atrasentan reduced endothelial heparanase expression and increased glycocalyx thickness in the presence of a diabetic milieu. Together these data point toward a role for the restoration of endothelial function and tissue homeostasis through the antialbuminuric effects of atrasentan, and they provide a mechanistic explanation for the clinical observations of reduced albuminuria with atrasentan in diabetic nephropathy. © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  1. Overexpression of TGF-β Inducible microRNA-143 in Zebrafish Leads to Impairment of the Glomerular Filtration Barrier by Targeting Proteoglycans.

    Science.gov (United States)

    Müller-Deile, Janina; Gellrich, Finn; Schenk, Heiko; Schroder, Patricia; Nyström, Jenny; Lorenzen, Johan; Haller, Hermann; Schiffer, Mario

    2016-01-01

    TGF-β is known as an important stress factor of podocytes in glomerular diseases. Apart from activation of direct pro-apoptotic pathways we wanted to analyze micro-RNA (miRs) driven regulation of components involved in the integrity of the glomerular filtration barrier induced by TGF-β. Since miR-143-3p (miR-143) is described as a TGF-β inducible miR in other cell types, we examined this specific miR and its ability to induce glomerular pathology. We analyzed miR-143 expression in cultured human podocytes after stimulation with TGF-β. We also microinjected zebrafish eggs with a miR-143 mimic or with morpholinos specific for its targets syndecan and versican and compared phenotype and proteinuria development. We detected a time dependent, TGF-β inducible expression of miR-143 in human podocytes. Targets of miR-143 relevant in glomerular biology are syndecans and versican, which are known components of the glycocalyx. We found that syndecan 1 and 4 were predominantly expressed in podocytes while syndecan 3 was largely expressed in glomerular endothelial cells. Versican could be detected in both cell types. After injection of a miR-143 mimic in zebrafish larvae, syndecan 3, 4 and versican were significantly downregulated. Moreover, miR-143 overexpression or versican knockdown by morpholino caused loss of plasma proteins, edema, podocyte effacement and endothelial damage. In contrast, knockdown of syndecan 3 and syndecan 4 had no effects on glomerular filtration barrier. Expression of versican and syndecan isoforms is indispensable for proper barrier function. Podocyte-derived miR-143 is a mediator for paracrine and autocrine cross talk between podocytes and glomerular endothelial cells and can alter expression of glomerular glycocalyx proteins. © 2016 The Author(s) Published by S. Karger AG, Basel.

  2. Mechanical challenges to the glomerular filtration barrier: adaptations and pathway to sclerosis.

    Science.gov (United States)

    Kriz, Wilhelm; Lemley, Kevin V

    2017-03-01

    Podocytes are lost as viable cells by detachment from the glomerular basement membrane (GBM), possibly due to factors such as pressure and filtrate flow. Distension of glomerular capillaries in response to increased pressure is limited by the elastic resistance of the GBM. The endothelium and podocytes adapt to changes in GBM area. The slit diaphragm (SD) seems to adjust by shuttling SD components between the SD and the adjacent foot processes (FPs), resulting in changes in SD area that parallel those in perfusion pressure.Filtrate flow tends to drag podocytes towards the urinary orifice by shear forces, which are highest within the filtration slits. The SD represents an atypical adherens junction, mechanically interconnecting the cytoskeleton of opposing FPs and tending to balance the shear forces.If under pathological conditions, increased filtrate flows locally overtax the attachment of FPs, the SDs are replaced by occluding junctions that seal the slits and the attachment of podocytes to the GBM is reinforced by FP effacement. Failure of these temporary adaptive mechanisms results in a steady process of podocyte detachment due to uncontrolled filtrate flows through bare areas of the GBM and, subsequently, the labyrinthine subpodocyte spaces, presenting as pseudocysts. In our view, shear stress due to filtrate flow-not capillary hydrostatic pressure-is the major challenge to the attachment of podocytes to the GBM.

  3. Wtip- and gadd45a-interacting protein dendrin is not crucial for the development or maintenance of the glomerular filtration barrier.

    Science.gov (United States)

    Xiao, Zhijie; Rodriguez, Patricia Q; He, Liqun; Betsholtz, Christer; Tryggvason, Karl; Patrakka, Jaakko

    2013-01-01

    Glomerular podocyte cells are critical for the function of the renal ultrafiltration barrier. Especially, the highly specialized cell-cell junction of podocytes, the slit diaphragm, has a central role in the filtration barrier. This is highlighted by the fact that mutations in molecular components of the slit diaphragm, including nephrin and Cd2-associated protein (Cd2ap), result in proteinuric diseases in man. Dendrin is a poorly characterized cytosolic component of the slit diaphragm in where it interacts with nephrin and Cd2ap. Dendrin is highly specific for the podocyte slit diaphragm, suggesting that it has a dedicated role in the glomerular filtration barrier. In this study, we have generated a dendrin knockout mouse line and explored the molecular interactions of dendrin. Dendrin-deficient mice were viable, fertile, and had a normal life span. Morphologically, the glomerulogenesis proceeded normally and adult dendrin-deficient mice showed normal glomerular histology. No significant proteinuria was observed. Following glomerular injury, lack of dendrin did not affect the severity of the damage or the recovery process. Yeast two-hybrid screen and co-immunoprecipitation experiments showed that dendrin binds to Wt1-interacting protein (Wtip) and growth arrest and DNA-damage-inducible 45 alpha (Gadd45a). Wtip and Gadd45a mediate gene transcription in the nucleus, suggesting that dendrin may have similar functions in podocytes. In line with this, we observed the relocation of dendrin to nucleus in adriamycin nephropathy model. Our results indicate that dendrin is dispensable for the function of the normal glomerular filtration barrier and that dendrin interacts with Wtip and Gadd45a.

  4. Wtip- and gadd45a-interacting protein dendrin is not crucial for the development or maintenance of the glomerular filtration barrier.

    Directory of Open Access Journals (Sweden)

    Zhijie Xiao

    Full Text Available Glomerular podocyte cells are critical for the function of the renal ultrafiltration barrier. Especially, the highly specialized cell-cell junction of podocytes, the slit diaphragm, has a central role in the filtration barrier. This is highlighted by the fact that mutations in molecular components of the slit diaphragm, including nephrin and Cd2-associated protein (Cd2ap, result in proteinuric diseases in man. Dendrin is a poorly characterized cytosolic component of the slit diaphragm in where it interacts with nephrin and Cd2ap. Dendrin is highly specific for the podocyte slit diaphragm, suggesting that it has a dedicated role in the glomerular filtration barrier. In this study, we have generated a dendrin knockout mouse line and explored the molecular interactions of dendrin. Dendrin-deficient mice were viable, fertile, and had a normal life span. Morphologically, the glomerulogenesis proceeded normally and adult dendrin-deficient mice showed normal glomerular histology. No significant proteinuria was observed. Following glomerular injury, lack of dendrin did not affect the severity of the damage or the recovery process. Yeast two-hybrid screen and co-immunoprecipitation experiments showed that dendrin binds to Wt1-interacting protein (Wtip and growth arrest and DNA-damage-inducible 45 alpha (Gadd45a. Wtip and Gadd45a mediate gene transcription in the nucleus, suggesting that dendrin may have similar functions in podocytes. In line with this, we observed the relocation of dendrin to nucleus in adriamycin nephropathy model. Our results indicate that dendrin is dispensable for the function of the normal glomerular filtration barrier and that dendrin interacts with Wtip and Gadd45a.

  5. Proteomic analysis of formalin-fixed paraffin-embedded glomeruli suggests depletion of glomerular filtration barrier proteins in two-kidney, one-clip hypertensive rats.

    Science.gov (United States)

    Finne, Kenneth; Vethe, Heidrun; Skogstrand, Trude; Leh, Sabine; Dahl, Tone D; Tenstad, Olav; Berven, Frode S; Reed, Rolf K; Vikse, Bjørn Egil

    2014-12-01

    It is well known that hypertension may cause glomerular damage, but the molecular mechanisms involved are still incompletely understood. In the present study, we used formalin-fixed paraffin-embedded (FFPE) tissue to investigate changes in the glomerular proteome in the non-clipped kidney of two-kidney one-clip (2K1C) hypertensive rats, with special emphasis on the glomerular filtration barrier. 2K1C hypertension was induced in 6-week-old Wistar Hannover rats (n = 6) that were sacrificed 23 weeks later and compared with age-matched sham-operated controls (n = 6). Tissue was stored in FFPE tissue blocks and later prepared on tissue slides for laser microdissection. Glomeruli without severe morphological damage were isolated, and the proteomes were analysed using liquid chromatography-tandem mass spectrometry. 2K1C glomeruli showed reduced abundance of proteins important for slit diaphragm complex, such as nephrin, podocin and neph1. The podocyte foot process had a pattern of reduced abundance of transmembrane proteins but unchanged abundances of the podocyte cytoskeletal proteins synaptopodin and α-actinin-4. Lower abundance of important glomerular basement membrane proteins was seen. Possible glomerular markers of damage with increased abundance in 2K1C were transgelin, desmin and acyl-coenzyme A thioesterase 1. Microdissection and tandem mass spectrometry could be used to investigate the proteome of isolated glomeruli from FFPE tissue. Glomerular filtration barrier proteins had reduced abundance in the non-clipped kidney of 2K1C hypertensive rats. © The Author 2014. Published by Oxford University Press on behalf of ERA-EDTA.

  6. Role of the VEGF--a signaling pathway in the glomerulus: evidence for crosstalk between components of the glomerular filtration barrier.

    Science.gov (United States)

    Eremina, Vera; Baelde, Hans J; Quaggin, Susan E

    2007-01-01

    Vascular endothelial growth factor is a major regulator of angiogenesis and vascular permeability [Carmeliet et al.: Nature 1996;380:435-439]. The podocyte, the outermost layer of the glomerular filtration barrier, produces large amounts of VEGF-A. The observation that levels of VEGF-A are altered in glomerular diseases, the identification of a link between pre-eclampsia and elevated levels of a circulating soluble VEGF receptor, and the entry of anti-VEGF therapies into the clinical arena have generated intense interest in the functional role of VEGF-A in the glomerulus. A variety of studies have been performed to address the role of VEGF-A signaling in the glomerulus. These include descriptions of expression patterns in human renal biopsies, cell culture studies to dissect paracrine versus autocrine signaling roles, and manipulation of VEGF-A expression in animal models using pharmacologic, biologic or genetic approaches. Exquisite dosage sensitivity to VEGF-A exists in the developing glomerulus as small reductions in the expression of VEGF-A lead to profound changes in glomerular structure and function in mice. The use of VEGF inhibitors is associated with damage to the glomerular endothelium in animal models and proteinuria in patients, suggesting that local VEGF-A production is also required for maintenance of this specialized vascular bed. Tight regulation of VEGF-A signaling is required for development and maintenance of the glomerular filtration barrier (GFB) and emphasizes the role of podocyte-endothelial crosstalk in the glomerulus. The relative contributions of various VEGF-A isoforms, the role of autocrine signaling in vivo and identification of factors and mechanisms that regulate constitutive expression, storage and delivery of VEGF-A in the glomerulus are still under investigation. Copyright 2007 S. Karger AG, Basel.

  7. The Rac-specific exchange factors Dock1 and Dock5 are dispensable for the establishment of the glomerular filtration barrier in vivo.

    Science.gov (United States)

    Laurin, Mélanie; Dumouchel, Annie; Fukui, Yoshinori; Côté, Jean-François

    2013-01-01

    Podocytes are specialized kidney cells that form the kidney filtration barrier through the connection of their foot processes. Nephrin and Neph family transmembrane molecules at the surface of podocytes interconnect to form a unique type of cell-cell junction, the slit diaphragm, which acts as a molecular sieve. The cytoplasmic tails of Nephrin and Neph mediate cytoskeletal rearrangement that contributes to the maintenance of the filtration barrier. Nephrin and Neph1 orthologs are essential to regulate cell-cell adhesion and Rac-dependent actin rearrangement during Drosophila myoblast fusion. We hypothesized here that molecules regulating myoblast fusion in Drosophila could contribute to signaling downstream of Nephrin and Neph1 in podocytes. We found that Nephrin engagement promoted recruitment of the Rac exchange factor Dock1 to the membrane. Furthermore, Nephrin overexpression led to lamellipodia formation that could be blocked by inhibiting Rac1 activity. We generated in vivo mouse models to investigate whether Dock1 and Dock5 contribute to the formation and maintenance of the kidney filtration barrier. Our results indicate that while Dock1 and Dock5 are expressed in podocytes, their functions are not essential for the development of the glomerular filtration barrier. Furthermore, mice lacking Dock1 were not protected from LPS-induced podocyte effacement. Our data suggest that Dock1 and Dock5 are not the important exchange factors regulating Rac activity during the establishment and maintenance of the glomerular barrier.

  8. Impact of swelling characteristics on the permselective ...

    Science.gov (United States)

    The removal of water from organic solvents and biofuels, including lower alcohols (i.e., methanol, ethanol, propanol, and butanol), is necessary for the production, blending, and reuse of those organic compounds. Water forms an azeotrope with many hydrophilic solvents, complicating the separation of water/solvent mixtures. The use of water-selective membranes in a pervaporation or vapor permeation process enables the removal of water from the solvents, even when an azeotrope is present. Common hydrophilic polymer membranes often swell in water, resulting in permeabilities and selectivities that are dependent on the water content of the feed mixture. Recent work has shown the benefit of overcoating a hydrophilic water-permselective membrane with a non-swelling perfluoropolymer film [1,2]. The perfluoropolymer layer reduces the activity of water the hydrophilic polymer layer experiences, thereby reducing swelling in that layer and increasing the water selectivity of the multi-layer membrane relative to the selectivity of the base hydrophilic polymer, usually at the expense of permeability. In this work, the effect of overcoating the hydrophilic layer with polymer films of various swelling characteristics was modelled. Top layers that swell in the solvent offer some advantages, particularly with regard to the water permeance of the multi-layer composite. 1. Huang, Y.; Baker, R. W.; Wijmans, J. G. Perfluoro-coated hydrophilic membranes with improved selectivity. In

  9. Glomerular Diseases

    Science.gov (United States)

    ... is called a glomerulus , which comes from the Greek word meaning filter. The plural form of the ... primary indicator of Alport syndrome is a family history of chronic glomerular disease, although it may also ...

  10. Protective clothing based on permselective membrane and carbon adsorption

    Energy Technology Data Exchange (ETDEWEB)

    Baker, R.

    1995-03-01

    The objective of this program is to develop improved protective clothing for use by workers engaged in decomissioning and decontamination of former DOE sites. The proposed technology concerns a new protective clothing fabric that combines a permselective membrane layer (for water transmission and breathability) with a sorptive layer.

  11. The role of packaging film permselectivity in modified atmosphere packaging.

    Science.gov (United States)

    Al-Ati, Tareq; Hotchkiss, Joseph H

    2003-07-02

    Modified atmosphere packaging (MAP) is commercially used to increase the shelf life of packaged produce by reducing the produce respiration rate, delaying senescence, and inhibiting the growth of many spoilage organisms, ultimately increasing product shelf life. MAP systems typically optimize O(2) levels to achieve these effects while preventing anaerobic fermentation but fail to optimize CO(2) concentrations. Altering film permselectivity (i.e., beta, which is the ratio of CO(2)/O(2) permeation coefficients) could be utilized to concurrently optimize levels of both CO(2) and O(2) in MAP systems. We investigated the effect of modifying film permselectivity on the equilibrium gas composition of a model MAP produce system packaged in containers incorporating modified poly(ethylene) ionomer films with CO(2)/O(2) permselectivites between 4-5 and 0.8-1.3. To compare empirical to calculated data of the effect of permselectivity on the equilibrium gas composition of the MAP produce system, a mathematical model commonly used to optimize MAP of respiring produce was applied. The calculated gas composition agreed with observed values, using empirical respiration data from fresh cut apples as a test system and permeability data from tested and theoretical films. The results suggest that packaging films with CO(2)/O(2) permselectivities lower than those commercially available (<3) would further optimize O(2) and CO(2) concentration in MAP of respiring produce, particularly highly respiring and minimally processed produce.

  12. Ionic Resistance and Permselectivity Tradeoffs in Anion Exchange Membranes

    KAUST Repository

    Geise, Geoffrey M.

    2013-10-23

    Salinity gradient energy technologies, such as reverse electrodialysis (RED) and capacitive mixing based on Donnan potential (Capmix CDP), could help address the global need for noncarbon-based energy. Anion exchange membranes (AEMs) are a key component in these systems, and improved AEMs are needed in order to optimize and extend salinity gradient energy technologies. We measured ionic resistance and permselectivity properties of quaternary ammonium-functionalized AEMs based on poly(sulfone) and poly(phenylene oxide) polymer backbones and developed structure-property relationships between the transport properties and the water content and fixed charge concentration of the membranes. Ion transport and ion exclusion properties depend on the volume fraction of water in the polymer membrane, and the chemical nature of the polymer itself can influence fine-tuning of the transport properties to obtain membranes with other useful properties, such as chemical and dimensional stability. The ionic resistance of the AEMs considered in this study decreased by more than 3 orders of magnitude (i.e., from 3900 to 1.6 Ω m) and the permselectivity decreased by 6% (i.e., from 0.91 to 0.85) as the volume fraction of water in the polymer was varied by a factor of 3.8 (i.e., from 0.1 to 0.38). Water content was used to rationalize a tradeoff relationship between the permselectivity and ionic resistance of these AEMs whereby polymers with higher water content tend to have lower ionic resistance and lower permselectivity. The correlation of ion transport properties with water volume fraction and fixed charge concentration is discussed with emphasis on the importance of considering water volume fraction when interpreting ion transport data. © 2013 American Chemical Society.

  13. Bioactivity of permselective PVA hydrogels with mixed ECM analogues.

    Science.gov (United States)

    Nafea, Eman H; Poole-Warren, Laura A; Martens, Penny J

    2015-12-01

    The presentation of multiple biological cues, which simulate the natural in vivo cell environment within artificial implants, has recently been identified as crucial for achieving complex cellular functions. The incorporation of two or more biological cues within a largely synthetic network can provide a simplified model of multifunctional ECM presentation to encapsulated cells. Therefore, the aim of this study was to examine the effects of simultaneously and covalently incorporating two dissimilar biological molecules, heparin and gelatin, within a PVA hydrogel. PVA was functionalized with 7 and 20 methacrylate functional groups per chain (FG/c) to tailor the permselectivity of UV photopolymerized hydrogels. Both heparin and gelatin were covalently incorporated into PVA at an equal ratio resulting in a final PVA:heparin:gelatin composition of 19:0.5:0.5. The combination of both heparin and gelatin within a PVA network has proven to be stable over time without compromising the PVA base characteristics including its permselectivity to different proteins. Most importantly, this combination of ECM analogues supplemented PVA with the dual functionalities of promoting cellular adhesion and sequestering growth factors essential for cellular proliferation. Multi-functional PVA hydrogels with synthetically controlled network characteristics and permselectivity show potential in various biomedical applications including artificial cell implants. © 2015 Wiley Periodicals, Inc.

  14. High glucose increases glomerular filtration barrier permeability by activating protein kinase G type Iα subunits in a Nox4-dependent manner.

    Science.gov (United States)

    Piwkowska, Agnieszka; Rogacka, Dorota; Audzeyenka, Irena; Angielski, Stefan; Jankowski, Maciej

    2014-01-01

    Hyperglycemia is a primary factor that disturbs podocyte function in the glomerular filtration process; this disturbance leads to the development of diabetic nephropathy, and ultimately, renal failure. Podocyte function may also be altered by biological agents that modify protein kinase activity, including the cGMP-activated protein kinase type Iα (PKGIα). We hypothesized that hyperglycemia-induced podocyte protein hyperpermeability was dependent on PKGIα activation, and that PKGIα was activated via dimerization induced by reactive oxygen species. This hypothesis was investigated in rat podocytes cultured in high glucose (HG, 30 mM). Protein expression was measured with Western blot and immunofluorescence. Podocyte permeability was measured with a transmembrane albumin flux assay. We found that HG increased podocyte permeability in long-term incubations (1, 3, and 5 days); permeability was increased by 66% on day 5. This effect was abolished with apocynin, a NAD(P)H inhibitor, and Rp-8-Br-cGMPS, a PKG inhibitor. It was also abolished by introducing small interfering RNAs (siRNAs) against Nox4 and PKGIα into cultured podocytes. Furthermore, HG increased PKGIα dimerization by 138% (0.23 ± 0.04 vs. 0.54 ± 0.09; Pfiltration barrier via Nox4-dependent PKGIα dimerization. © 2013 Published by Elsevier Inc.

  15. Janus kinase 2/signal transducer and activator of transcription 3 inhibitors attenuate the effect of cardiotrophin-like cytokine factor 1 and human focal segmental glomerulosclerosis serum on glomerular filtration barrier.

    Science.gov (United States)

    Sharma, Mukut; Zhou, Jianping; Gauchat, Jean-François; Sharma, Ram; McCarthy, Ellen T; Srivastava, Tarak; Savin, Virginia J

    2015-10-01

    Recurrence of idiopathic focal segmental glomerulosclerosis (FSGS) after renal transplantation is believed to be caused by a circulating factor(s). We detected cardiotrophin-like cytokine factor 1 (CLCF1), a member of the interleukin 6 family, in the plasma from patients with recurrent FSGS. We hypothesized that CLCF1 contributes to the effect of FSGS serum on the glomerular filtration barrier in vitro. Presently, we studied the effect of CLCF1 on isolated rat glomeruli using an in vitro assay of albumin permeability (P(alb)). CLCF1 (0.05-100 ng/mL) increased P(alb) and caused maximal effect at 5-10 ng/mL (P glomerular filtration barrier. We speculate that albuminuria in FSGS is related to qualitative or quantitative changes in the CLCF1-CRLF1 complex, and that JAK2 or STAT3 inhibitors may be novel therapeutic agents to treat FSGS. Published by Elsevier Inc.

  16. Protective clothing based on permselective membrane and carbon adsorption

    International Nuclear Information System (INIS)

    Gottschlich, D.; Baker, R.

    1995-01-01

    This paper is a description of Phase I of the US DOE's program to develop improved protective clothing for use by workers engaged in decommissioning and decontamination of former DOE sites, including those used for atomic weapons research and production. Membrane Technology and Research has been developing the clothing with an innovative feature of an ultrathin, permselective outer membrane that is extremely permeable to water but impermeable to toxic organic compounds. Phase I (as described herein) includes fabric optimization, commercial-scale fabric production, and prototype suit evaluation. This phase is complete, with the results discussed in this document

  17. Specific ion effects on membrane potential and the permselectivity of ion exchange membranes

    KAUST Repository

    Geise, Geoffrey M.

    2014-08-26

    © the Partner Organisations 2014. Membrane potential and permselectivity are critical parameters for a variety of electrochemically-driven separation and energy technologies. An electric potential is developed when a membrane separates electrolyte solutions of different concentrations, and a permselective membrane allows specific species to be transported while restricting the passage of other species. Ion exchange membranes are commonly used in applications that require advanced ionic electrolytes and span technologies such as alkaline batteries to ammonium bicarbonate reverse electrodialysis, but membranes are often only characterized in sodium chloride solutions. Our goal in this work was to better understand membrane behaviour in aqueous ammonium bicarbonate, which is of interest for closed-loop energy generation processes. Here we characterized the permselectivity of four commercial ion exchange membranes in aqueous solutions of sodium chloride, ammonium chloride, sodium bicarbonate, and ammonium bicarbonate. This stepwise approach, using four different ions in aqueous solution, was used to better understand how these specific ions affect ion transport in ion exchange membranes. Characterization of cation and anion exchange membrane permselectivity, using these ions, is discussed from the perspective of the difference in the physical chemistry of the hydrated ions, along with an accompanying re-derivation and examination of the basic equations that describe membrane potential. In general, permselectivity was highest in sodium chloride and lowest in ammonium bicarbonate solutions, and the nature of both the counter- and co-ions appeared to influence measured permselectivity. The counter-ion type influences the binding affinity between counter-ions and polymer fixed charge groups, and higher binding affinity between fixed charge sites and counter-ions within the membrane decreases the effective membrane charge density. As a result permselectivity decreases. The

  18. The formation of quiescent glomerular endothelial cell monolayer in vitro is strongly dependent on the choice of extracellular matrix coating

    Energy Technology Data Exchange (ETDEWEB)

    Pajęcka, Kamilla, E-mail: kpaj@novonordisk.com [Global Research, Novo Nordisk A/S, Måløv (Denmark); Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus (Denmark); Nielsen, Malik Nygaard [Global Research, Novo Nordisk A/S, Måløv (Denmark); Hansen, Troels Krarup [Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus (Denmark); Williams, Julie M. [Global Research, Novo Nordisk A/S, Måløv (Denmark)

    2017-04-01

    Background and aims: Nephropathy involves pathophysiological changes to the glomerulus. The primary glomerular endothelial cells (GEnCs) have emerged as an important tool for studying glomerulosclerotic mechanisms and in the screening process for drug-candidates. The success of the studies is dependent on the quality of the cell model. Therefore, we set out to establish an easy, reproducible model of the quiescent endothelial monolayer with the use of commercially available extracellular matrices (ECMs). Methods: Primary hGEnCs were seeded on various ECMs. Cell adhesion was monitored by an impedance sensing system. The localization of junctional proteins was assessed by immunofluorescence and the barrier function by passage of fluorescent dextrans and magnitude of VEGF response. Results: All ECM matrices except recombinant human laminin 111 (rhLN111) supported comparable cell proliferation. Culturing hGEnCs on rhLN521, rhLN511 or fibronectin resulted in a physiologically relevant barrier to 70 kDa dextrans which was 82% tighter than that formed on collagen type IV. Furthermore, only hGEnCs cultured on rhLN521 or rhLN511 showed plasma-membrane localized zonula occludens-1 and vascular endothelial cadherin indicative of proper tight and adherens junctions (AJ). Conclusion: We recommend culturing hGEnCs on the mature glomerular basement membrane laminin - rhLN521 – which, as the only commercially available ECM, promotes all of the characteristics of the quiescent hGEnC monolayer: cobblestone morphology, well-defined AJs and physiological perm-selectivity. - Highlights: • rhLN521, rhLN511 and hFN assure physiologically relevant permeability. • rhLN521 and rhLN511 ensure best cell morphology and adherens junction formation. • Collagen IV and I based coating results in disorganized hGEnC monolayer. • Physiologically relevant ECM may lead to down-regulation of self-produced matrices.

  19. The formation of quiescent glomerular endothelial cell monolayer in vitro is strongly dependent on the choice of extracellular matrix coating

    International Nuclear Information System (INIS)

    Pajęcka, Kamilla; Nielsen, Malik Nygaard; Hansen, Troels Krarup; Williams, Julie M.

    2017-01-01

    Background and aims: Nephropathy involves pathophysiological changes to the glomerulus. The primary glomerular endothelial cells (GEnCs) have emerged as an important tool for studying glomerulosclerotic mechanisms and in the screening process for drug-candidates. The success of the studies is dependent on the quality of the cell model. Therefore, we set out to establish an easy, reproducible model of the quiescent endothelial monolayer with the use of commercially available extracellular matrices (ECMs). Methods: Primary hGEnCs were seeded on various ECMs. Cell adhesion was monitored by an impedance sensing system. The localization of junctional proteins was assessed by immunofluorescence and the barrier function by passage of fluorescent dextrans and magnitude of VEGF response. Results: All ECM matrices except recombinant human laminin 111 (rhLN111) supported comparable cell proliferation. Culturing hGEnCs on rhLN521, rhLN511 or fibronectin resulted in a physiologically relevant barrier to 70 kDa dextrans which was 82% tighter than that formed on collagen type IV. Furthermore, only hGEnCs cultured on rhLN521 or rhLN511 showed plasma-membrane localized zonula occludens-1 and vascular endothelial cadherin indicative of proper tight and adherens junctions (AJ). Conclusion: We recommend culturing hGEnCs on the mature glomerular basement membrane laminin - rhLN521 – which, as the only commercially available ECM, promotes all of the characteristics of the quiescent hGEnC monolayer: cobblestone morphology, well-defined AJs and physiological perm-selectivity. - Highlights: • rhLN521, rhLN511 and hFN assure physiologically relevant permeability. • rhLN521 and rhLN511 ensure best cell morphology and adherens junction formation. • Collagen IV and I based coating results in disorganized hGEnC monolayer. • Physiologically relevant ECM may lead to down-regulation of self-produced matrices.

  20. Glomerular filtration rate

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/007305.htm Glomerular filtration rate To use the sharing features on this page, please enable JavaScript. Glomerular filtration rate (GFR) is a test used to check ...

  1. TNF-mediated damage to glomerular endothelium is an important determinant of acute kidney injury in sepsis.

    Science.gov (United States)

    Xu, Chang; Chang, Anthony; Hack, Bradley K; Eadon, Michael T; Alper, Seth L; Cunningham, Patrick N

    2014-01-01

    Severe sepsis is often accompanied by acute kidney injury (AKI) and albuminuria. Here we studied whether the AKI and albuminuria associated with lipopolysaccharide (LPS) treatment in mice reflects impairment of the glomerular endothelium with its associated endothelial surface layer. LPS treatment decreased the abundance of endothelial surface layer heparan sulfate proteoglycans and sialic acid, and led to albuminuria likely reflecting altered glomerular filtration permselectivity. LPS treatment decreased the glomerular filtration rate (GFR), while also causing significant ultrastructural alterations in the glomerular endothelium. The density of glomerular endothelial cell fenestrae was 5-fold lower, whereas the average fenestrae diameter was 3-fold higher in LPS-treated than in control mice. The effects of LPS on the glomerular endothelial surface layer, endothelial cell fenestrae, GFR, and albuminuria were diminished in TNF receptor 1 (TNFR1) knockout mice, suggesting that these LPS effects are mediated by TNF-α activation of TNFR1. Indeed, intravenous administration of TNF decreased GFR and led to loss of glomerular endothelial cell fenestrae, increased fenestrae diameter, and damage to the glomerular endothelial surface layer. LPS treatment decreased kidney expression of vascular endothelial growth factor (VEGF). Thus, our findings confirm the important role of glomerular endothelial injury, possibly by a decreased VEGF level, in the development and progression of AKI and albuminuria in the LPS model of sepsis in the mouse.

  2. Glomerular Disease in Women

    Directory of Open Access Journals (Sweden)

    Kate Wiles

    2018-03-01

    Full Text Available Gender differences exist in the prevalence of glomerular diseases. Data based on histological diagnosis underestimate the prevalence of preeclampsia, which is almost certainly the commonest glomerular disease in the world, and uniquely gender-specific. Glomerular disease affects fertility via disease activity, the therapeutic use of cyclophosphamide, and underlying chronic kidney disease. Techniques to preserve fertility during chemotherapy and risk minimization of artificial reproductive techniques are considered. The risks, benefits, and effectiveness of different contraceptive methods for women with glomerular disease are outlined. Glomerular disease increases the risk of adverse outcomes in pregnancy, including preeclampsia; yet, diagnosis of preeclampsia is complicated by the presence of hypertension and proteinuria that precede pregnancy. The role of renal biopsy in pregnancy is examined, in addition to the use of emerging angiogenic biomarkers. The safety of drugs prescribed for glomerular disease in relation to reproductive health is detailed. The impact of both gender and pregnancy on long-term prognosis is discussed.

  3. PROTECTIVE CLOTHING BASED ON PERMSELECTIVE MEMBRANE AND CARBON ADSORPTION

    International Nuclear Information System (INIS)

    Wijmans, J.G.; Stull, J.O.

    2001-01-01

    The goal of this project was to develop chemical protective clothing for use by DOE decontamination and decommissioning workers that is sufficiently water vapor permeable to keep the workers cool, thereby enhancing their productivity. This report describes the results of Phase II of a two-phase project to complete development of the novel permselective material and to test protective clothing made from the fabric. In Phase I a novel material incorporating a nonporous hydrophilic polyvinylacohol (PVA) layer, which is water vapor permeable but relatively impermeable to organic vapors, was developed. The results of the Phase I tests showed that the chemical resistance of the MTR material is comparable to that of Saranex/Tyvek materials, and that the comfort properties are closer to those of Tyvek (as measured in terms of CLO and permeability). Chemical resistance was measured using permeation tests against liquid dichloromethane. Comfort properties were ascertained by measuring the water vapor transmission of the material and by sweating manikin tests on whole protective suits. In addition, a cost/benefit analysis demonstrated that use of MTR's material technology could result in significant improvements in work productivity and cost savings if protective clothing items made from the new material were used more than once. In Phase II, MTR undertook a program to optimize the performance and production engineering for the new material technology. A partnership was formed with Kimberly-Clark Corporation to assist with a detailed evaluation of the MTR technology, and MTR used the services of Mr. Jeff Stull, President of the consulting firm International Personnel Protection, Inc., who conducted a detailed economic and application analysis for the developed fabric. The protective fabric manufacturing steps were simplified significantly, resulting in a 30% reduction in manufacturing costs and eliminating the necessity for capital investment in production equipment

  4. PROTECTIVE CLOTHING BASED ON PERMSELECTIVE MEMBRANE AND CARBON ADSORPTION

    Energy Technology Data Exchange (ETDEWEB)

    J.G. Wijmans; J.O. Stull

    2001-11-07

    The goal of this project was to develop chemical protective clothing for use by DOE decontamination and decommissioning workers that is sufficiently water vapor permeable to keep the workers cool, thereby enhancing their productivity. This report describes the results of Phase II of a two-phase project to complete development of the novel permselective material and to test protective clothing made from the fabric. In Phase I a novel material incorporating a nonporous hydrophilic polyvinylacohol (PVA) layer, which is water vapor permeable but relatively impermeable to organic vapors, was developed. The results of the Phase I tests showed that the chemical resistance of the MTR material is comparable to that of Saranex/Tyvek materials, and that the comfort properties are closer to those of Tyvek (as measured in terms of CLO and permeability). Chemical resistance was measured using permeation tests against liquid dichloromethane. Comfort properties were ascertained by measuring the water vapor transmission of the material and by sweating manikin tests on whole protective suits. In addition, a cost/benefit analysis demonstrated that use of MTR's material technology could result in significant improvements in work productivity and cost savings if protective clothing items made from the new material were used more than once. In Phase II, MTR undertook a program to optimize the performance and production engineering for the new material technology. A partnership was formed with Kimberly-Clark Corporation to assist with a detailed evaluation of the MTR technology, and MTR used the services of Mr. Jeff Stull, President of the consulting firm International Personnel Protection, Inc., who conducted a detailed economic and application analysis for the developed fabric. The protective fabric manufacturing steps were simplified significantly, resulting in a 30% reduction in manufacturing costs and eliminating the necessity for capital investment in production equipment

  5. Pathology of glomerular lipidosis.

    Science.gov (United States)

    Sato, Hiroshi; Takahashi, Nobuyuki; Sato, Emiko; Kisu, Kiyomi; Ito, Sadayoshi; Saito, Takao

    2014-04-01

    Glomerular lipid deposition is sometimes associated with a particular kind of lipid metabolism disturbance. Ultrastructural analyses using electron microscopy often indicate a disease-specific aspect of intraglomerular lipid distribution.

  6. Glomerular Lipidosis in Dogs.

    Science.gov (United States)

    Kohnken, Rebecca A; Amerman, Hayley; Brown, Cathy A; Furrow, Eva; Lees, George E; Cianciolo, Rachel E

    2017-09-01

    Glomerular lipidosis (GL) is characterized by dilated glomerular capillary loops containing lipid-laden cells (foam cells). Previously, GL was considered to be an incidental finding because affected dogs were typically not azotemic. However, the International Renal Interest Society staging system for canine chronic kidney disease has increased the awareness of other clinical parameters (eg, proteinuria and hypertension) that should be included in the assessment of renal function. As such, the aim of this study was to determine clinical abnormalities and concurrent renal lesions in dogs with GL. GL was identified in renal biopsies from 46 dogs evaluated by the International Veterinary Renal Pathology Service. GL was the sole diagnosis in 5 of 46 cases (11%), all of which were proteinuric. All 5 dogs had at least 1 additional clinicopathologic abnormality consistent with renal disease, including hypertension (4), azotemia (3), and/or hypoalbuminemia (2). The remaining 41 dogs had GL in combination with other glomerular lesions, the most common being focal segmental glomerulosclerosis (16, 35%), lesions consistent with juvenile nephropathy (8, 17%), and glomerular amyloidosis (5, 11%). Overall, dogs with severe GL were younger than were those with mild GL ( P < .001). The percentage of glomeruli affected by GL differed by concurrent diagnoses ( P = .034), with the highest percentage of affected glomeruli in dogs with GL alone or those with concurrent juvenile nephropathy. These findings suggest that GL should be a recognized histologic phenotype of glomerular injury associated with clinical renal dysfunction and/or juvenile nephropathies.

  7. Glomerular nephrotoxicity of aminoglycosides

    International Nuclear Information System (INIS)

    Martinez-Salgado, Carlos; Lopez-Hernandez, Francisco J.; Lopez-Novoa, Jose M.

    2007-01-01

    Aminoglycoside antibiotics are the most commonly used antibiotics worldwide in the treatment of Gram-negative bacterial infections. However, aminoglycosides induce nephrotoxicity in 10-20% of therapeutic courses. Aminoglycoside-induced nephrotoxicity is characterized by slow rises in serum creatinine, tubular necrosis and marked decreases in glomerular filtration rate and in the ultrafiltration coefficient. Regulation of the ultrafiltration coefficient depends on the activity of intraglomerular mesangial cells. The mechanisms responsible for tubular nephrotoxicity of aminoglycosides have been intensively reviewed previously, but glomerular toxicity has received less attention. The purpose of this review is to critically assess the published literature regarding the toxic mechanisms of action of aminoglycosides on renal glomeruli and mesangial cells. The main goal of this review is to provide an actualized and mechanistic vision of pathways involved in glomerular toxic effects of aminoglycosides

  8. A permselective CeO{sub x} coating to improve the stability of oxygen evolution electrocatalysts

    Energy Technology Data Exchange (ETDEWEB)

    Obata, Keisuke; Takanabe, Kazuhiro [King Abdullah University of Science and Technology (KAUST), KAUST Catalysis Center (KCC) and Physical Sciences and Engineering Division PSE, Thuwal (Saudi Arabia)

    2018-02-05

    Highly active NiFeO{sub x} electrocatalysts for the oxygen evolution reaction (OER) suffer gradual deactivation with time owing to the loss of Fe species from the active sites into solution during catalysis. The anodic deposition of a CeO{sub x} layer prevents the loss of such Fe species from the OER catalysts, achieving a highly stable performance. The CeO{sub x} layer does not affect the OER activity of the catalyst underneath but exhibits unique permselectivity, allowing the permeation of OH{sup -} and O{sub 2} through while preventing the diffusion of redox ions through the layer to function as a selective O{sub 2}-evolving electrode. The use of such a permselective protective layer provides a new strategy for improving the durability of electrocatalysts. (copyright 2018 Wiley-VCH Verlag GmbH and Co. KGaA, Weinheim)

  9. A permselective CeOx coating to improve the stability of oxygen evolution electrocatalysts

    International Nuclear Information System (INIS)

    Obata, Keisuke; Takanabe, Kazuhiro

    2018-01-01

    Highly active NiFeO x electrocatalysts for the oxygen evolution reaction (OER) suffer gradual deactivation with time owing to the loss of Fe species from the active sites into solution during catalysis. The anodic deposition of a CeO x layer prevents the loss of such Fe species from the OER catalysts, achieving a highly stable performance. The CeO x layer does not affect the OER activity of the catalyst underneath but exhibits unique permselectivity, allowing the permeation of OH - and O 2 through while preventing the diffusion of redox ions through the layer to function as a selective O 2 -evolving electrode. The use of such a permselective protective layer provides a new strategy for improving the durability of electrocatalysts. (copyright 2018 Wiley-VCH Verlag GmbH and Co. KGaA, Weinheim)

  10. A Permselective CeOx Coating Improves the Stability of Oxygen Evolution Electrocatalysts

    KAUST Repository

    Obata, Keisuke

    2017-12-05

    Highly active NiFeOx electrocatalysts for the oxygen evolution reaction (OER) suffer gradual deactivation with time due to the loss of Fe species from the active sites into solution during catalysis. Here, we describe the anodic deposition of a CeOx layer that prevents the loss of such Fe species from the OER catalysts, achieving a highly stable performance. The CeOx layer does not affect the OER activity of the catalyst underneath but exhibits unique permselectivity, allowing the permeation of OH- and O2 through while preventing the diffusion of redox ions through the layer to function as a selective O2-evolving electrode. The use of such permselective protective layer provides a new strategy for improving the durability of electrocatalysts.

  11. Glomerular Damage in Experimental Proliferative Glomerulonephritis Under Glomerular Capillary Hypertension

    Directory of Open Access Journals (Sweden)

    Pei-Rong Wang

    2015-03-01

    Full Text Available Background/Aims: Immunologically and hemodynamically mediated the destruction of glomerular architecture is thought to be the major causes of end-stage renal failure. The purpose of this study is to evaluate the effect of glomerular hypertension on glomerular injury and the progression of glomerular sclerosis after Thy-1 nephritis was induced. Method: Thy-1 nephritis was induced in the stroke-prone spontaneously hypertensive rat strain (SHR-SP (group SP and in age-matched Wistar-Kyoto (WKY (group WKY rats, following unilateral nephrectomy (UNX, and a vehicle was injected alone in UNX SHR-SP as control (group SC. Result: The degree of glomerular damage in response to a single dose of anti-thy-1 antibody, and its functional consequences (eg. proteinuria, diminished GFR are more pronounced in group SP than normotensive group WKY and hypertensive group SC without mesangial cell injury. While normotensive group WKY rats recovered completely from mesangial cell injury on day 28-42, glomeruli in group SP kept on persistent macrophage infiltration, α-SMA expression on day 42-56. In addition, glomerular capillary repair with the GECs was rarely seen in pronouncedly proliferative and sclerostic areas. The incidence of glomerular sclerosis and the level of proteinuria were markedly increased by day 56 in the group SP. Conclusions: Our results demonstrate that glomerular hypertension aggravate glomerular damage and glomerulosclerosis in this model of Thy 1 nephritis.

  12. Effect of geometry on concentration polarization in realistic heterogeneous permselective systems.

    Science.gov (United States)

    Green, Yoav; Shloush, Shahar; Yossifon, Gilad

    2014-04-01

    This study extends previous analytical solutions of concentration polarization occurring solely in the depleted region, to the more realistic geometry consisting of a three-dimensional (3D) heterogeneous ion-permselective medium connecting two opposite microchambers (i.e., a three-layer system). Under the local electroneutrality approximation, the separation of variable methods is used to derive an analytical solution of the electrodiffusive problem for the two opposing asymmetric microchambers. The assumption of an ideal permselective medium allows for the analytic calculation of the 3D concentration and electric potential distributions as well as a current-voltage relation. It is shown that any asymmetry in the microchamber geometries will result in current rectification. Moreover, it is demonstrated that for non-negligible microchamber resistances, the conductance does not exhibit the expected saturation at low concentrations but instead shows a continuous decrease. The results are intended to facilitate a more direct comparison between theory and experiments, as now the voltage drop is across a realistic 3D and three-layer system.

  13. Cross-Linkable Polyimide Membranes for Improved Plasticization Resistance and Permselectivity in Sour Gas Separations

    KAUST Repository

    Kraftschik, Brian

    2013-09-10

    A series of cross-linkable membrane materials based on the 6FDA-DAM:DABA (3:2) polyimide backbone were synthesized for improved sour gas separation performance, in terms of both membrane stability and permselectivity. Short-chain poly(ethylene glycol) (PEG) molecules were used as cross-linking agents in an esterification-based cross-linking reaction. Pure and mixed gas permeation and pure gas sorption experiments were performed on dense films of these materials. Compared to unmodified 6FDA-DAM:DABA (3:2), higher sour gas permselectivity and membrane stability were achieved under aggressive feed conditions. H2S-induced plasticization was not evident until pure H2S feed pressures greater than approximately 6-8 bar. Pure CO 2-induced plasticization only occurred at feed pressures greater than about 25 bar. Under mixed gas feed conditions with 20% H2S, 20% CO2, and 60% CH4 at 35 C, attractive selectivities above 22 and 27 for H2S/CH4 and CO2/CH4, respectively, were observed for a feed pressure of 62 bar with both triethylene glycol and tetraethylene glycol cross-linking agents. © 2013 American Chemical Society.

  14. Controlling the transport of cations through permselective mesoporous alumina layers by manipulation of electric field and ionic strength

    NARCIS (Netherlands)

    Schmuhl, R.; Keizer, Klaas; van den Berg, Albert; ten Elshof, Johan E.; Blank, David H.A.

    2004-01-01

    The electric field-driven transport of ions through supported mesoporous γ-alumina membranes was investigated. The influence of ion concentration, ion valency, pH, ionic strength, and electrolyte composition on transport behavior was determined. The permselectivity of the membrane was found to be

  15. ZIF-78 membrane derived from amorphous precursors with permselectivity for cyclohexanone/cyclohexanol mixture

    KAUST Repository

    Fan, Lili

    2014-07-01

    Cyclohexanone and cyclohexanol are products of selective oxidation of cyclohexane. They are important industrial intermediates and difficult to be separated due to their close boiling points. In this work, well-intergrown ZIF-78 membrane was successfully synthesized on the porous silica substrate by secondary growth method and applied for separation of cyclohexanone/cyclohexanol mixture for the first time. Meanwhile, a facile method for seeding procedure was developed by utilizing the amorphous ZIF-78 precursors to provide better-distributed nucleation sites. Both XRD and SEM results confirmed the good quality of the membrane. The pervaporation separation of cyclohexanone/ cyclohexanol mixture were carried out at room temperature with permselectivity of 1:2 and total flux around 8.7 × 10-2 kg m-2 h-1. © 2013 Elsevier Inc. All rights reserved.

  16. The Beneficial Role of Retinoids in Glomerular Disease

    Directory of Open Access Journals (Sweden)

    Sandeep eMallipattu

    2015-03-01

    Full Text Available The primary etiology of CKD is a direct consequence of initial dysfunction and injury of the glomerulus, the main filtration system. Podocytes are terminally differentiated epithelial cells in the glomerulus, whose major function is the maintenance of this renal filtration barrier. Podocyte injury is implicated in many glomerular diseases including Focal Segmental Glomerular Sclerosis (FSGS and HIV-associated nephropathy (HIVAN. In many of these diseased conditions, the podocyte can either undergo dedifferentiation and proliferation, apoptosis, or cell detachment. Regardless of the initial type of injury, the podocyte ultimately loses its functional capacity to maintain the glomerular filtration barrier. Significant injury resulting in a loss of the podocytes and failure to maintain the renal filtration barrier contributes to progressive kidney disease. Consequently, therapies that prevent podocyte injury and promote their regeneration will have a major clinical impact on glomerular disease. Retinoic acid (RA, which is a derivative of vitamin A, has many cellular functions including induction of cell differentiation, regulation of apoptosis, and inhibition of inflammation and proliferation. RA is required for kidney development and is essential for cellular differentiation in the setting of podocyte injury. The mechanism by which RA directs its beneficial effects is multifactorial, ranging from its anti-inflammatory and anti-fibrotic effects to a direct effect of upregulating podocyte differentiation markers in the podocyte. The focus of this review is to provide an overview of RA in kidney development and glomerular disease. We also highlight the key mechanism(s by which RA restores podocyte differentiation markers and ameliorates glomerular disease.

  17. Corticosteroids decrease glomerular angiotensin receptors

    Energy Technology Data Exchange (ETDEWEB)

    Douglas, J.G.

    1987-03-01

    Angiotensin II (ANG II) receptors of glomerular mesangial cells are regulated in vivo by changes in Na balance, effects that are presumed to be secondary to changes in circulating ANG II. However, since changes in ANG II were accompanied by parallel changes in plasma aldosterone in all models tested, it is possible that aldosterone may have also participated in the modulation of glomerular ANG II receptors. To test this hypothesis, short-term aldosterone infusions within the physiological range were employed to favor actions that would be mediated through a high-affinity mineralocorticoid receptor. The glucocorticoid, dexamethasone, was also tested to determine the mineralocorticoid specificity of the response. Two infusion rates were associated with a decrease in glomerular /sup 125/I ANG II receptor density of 33 and 45%, respectively. Serum potassium and urinary Na/K ratio were lower in the aldosterone group. Spironolactone abolished the effect of aldosterone consistent with an action mediated through a specific mineralocorticoid receptor. These studies support the hypothesis that corticosteroids modulate glomerular ANG II receptors and validate the complexity of glomerular receptor modulation. The downregulation observed would be expected to diminish the ability of ANG II to influence glomerular hemodynamics in models such as mineralocorticoid and glucocorticoid-induced hypertension.

  18. Development of Pd Alloy Hydrogen Separation Membranes with Dense/Porous Hybrid Structure for High Hydrogen Perm-Selectivity

    Directory of Open Access Journals (Sweden)

    Jae-Yun Han

    2014-01-01

    Full Text Available For the commercial applications of hydrogen separation membranes, both high hydrogen selectivity and permeability (i.e., perm-selectivity are required. However, it has been difficult to fabricate thin, dense Pd alloy composite membranes on porous metal support that have a pore-free surface and an open structure at the interface between the Pd alloy films and the metal support in order to obtain the required properties simultaneously. In this study, we fabricated Pd alloy hydrogen separation membranes with dense/porous hybrid structure for high hydrogen perm-selectivity. The hydrogen selectivity of this membrane increased owing to the dense and pore-free microstructure of the membrane surface. The hydrogen permeation flux also was remarkably improved by the formation of an open microstructure with numerous open voids at the interface and by an effective reduction in the membrane thickness as a result of the porous structure formed within the Pd alloy films.

  19. Outcome of the acute glomerular injury in proliferative lupus nephritis

    Energy Technology Data Exchange (ETDEWEB)

    Chagnac, A.; Kiberd, B.A.; Farinas, M.C.; Strober, S.; Sibley, R.K.; Hoppe, R.; Myers, B.D. (Stanford Univ. Medical Center, CA (USA))

    1989-09-01

    Treatment with total lymphoid irradiation (TLI) and corticosteroids markedly reduced activity of systemic lupus erythematosis in 10 patients with diffuse proliferative lupus nephritis (DPLN) complicated by a nephrotic syndrome. Physiologic and morphometric techniques were used serially before, and 12 and 36 mo post-TLI to characterize the course of glomerular injury. Judged by a progressive reduction in the density of glomerular cells and immune deposits, glomerular inflammation subsided. A sustained reduction in the fractional clearance of albumin, IgG and uncharged dextrans of radius greater than 50 A, pointed to a parallel improvement in glomerular barrier size-selectivity. Corresponding changes in GFR were modest, however. A trend towards higher GFR at 12 mo was associated with a marked increase in the fraction of glomerular tuft area occupied by patent capillary loops as inflammatory changes receded. A late trend toward declining GFR beyond 12 mo was associated with progressive glomerulosclerosis, which affected 57% of all glomeruli globally by 36 mo post-TLI. Judged by a parallel increase in volume by 59%, remaining, patent glomeruli had undergone a process of adaptive enlargement. We propose that an increasing fraction of glomeruli continues to undergo progressive sclerosis after DPLN has become quiescent, and that the prevailing GFR depends on the extent to which hypertrophied remnant glomeruli can compensate for the ensuing loss of filtration surface area.

  20. Fouling prevention of peptides from a tryptic whey hydrolysate during electromembrane processes by use of monovalent ion permselective membranes

    OpenAIRE

    Persico, Mathieu; Bazinet, Laurent

    2017-01-01

    Peptide adsorption occurring on conventional anion- and cation-exchange membranes is one of the main technological locks in electrodialysis (ED) for hydrolysate demineralization. Hence, the peptide fouling of monovalent anion (MAP) and monovalent cation (MCP) permselective membranes was studied and compared to conventional membranes (AMX-SB and CMX-SB). It appeared that the main peptide sequences responsible for fouling were TPEVDDEALEKFDK, VAGTWY and VLVLDTDYK for both anionic membranes; and...

  1. Glomerular extracellular matrix components and integrins

    NARCIS (Netherlands)

    Sterk, L. M.; de Melker, A. A.; Kramer, D.; Kuikman, I.; Chand, A.; Claessen, N.; Weening, J. J.; Sonnenberg, A.

    1998-01-01

    It has become apparent that extracellular matrix components and their cellular receptors, the integrins, are important regulators of glomerular development and function. In this rapidly evolving field we studied the production of extracellular matrix components and integrins by rat glomerular

  2. Organogenesis of the kidney glomerulus: focus on the glomerular basement membrane.

    Science.gov (United States)

    Miner, Jeffrey H

    2011-01-01

    The glomerular basement membrane (GBM) is a crucial component of the kidney's filtration barrier that separates the vasculature from the urinary space. During glomerulogenesis, the GBM is formed from fusion of two distinct basement membranes, one synthesized by the glomerular epithelial cell (podocyte) and the other by the glomerular endothelial cell. The main components of the GBM are laminin-521 (α5β2γ1), collagen α3α4α5(IV), nidogen and the heparan sulfate proteoglycan, agrin. By studying mice lacking specific GBM components, we have shown that during glomerulogenesis, laminin is the only one that is required for GBM integrity and in turn, the GBM is required for completion of glomerulogenesis and glomerular vascularization. In addition, our results from laminin β2-null mice suggest that laminin-521, and thus the GBM, contribute to the establishment and maintenance of the glomerular filtration barrier to plasma albumin. In contrast, mutations that affect GBM collagen IV or agrin do not impair glomerular development or cause immediate leakage of plasma proteins. However, collagen IV mutation, which causes Alport syndrome and ESRD in humans, leads to gradual damage to the GBM that eventually leads to albuminuria and renal failure. These results highlight the importance of the GBM for establishing and maintaining a perfectly functioning, highly selective glomerular filter.

  3. An in vitro model of the glomerular capillary wall using electrospun collagen nanofibres in a bioartificial composite basement membrane.

    Directory of Open Access Journals (Sweden)

    Sadie C Slater

    Full Text Available The filtering unit of the kidney, the glomerulus, contains capillaries whose walls function as a biological sieve, the glomerular filtration barrier. This comprises layers of two specialised cells, glomerular endothelial cells (GEnC and podocytes, separated by a basement membrane. Glomerular filtration barrier function, and dysfunction in disease, remains incompletely understood, partly due to difficulties in studying the relevant cell types in vitro. We have addressed this by generation of unique conditionally immortalised human GEnC and podocytes. However, because the glomerular filtration barrier functions as a whole, it is necessary to develop three dimensional co-culture models to maximise the benefit of the availability of these cells. Here we have developed the first two tri-layer models of the glomerular capillary wall. The first is based on tissue culture inserts and provides evidence of cell-cell interaction via soluble mediators. In the second model the synthetic support of the tissue culture insert is replaced with a novel composite bioartificial membrane. This consists of a nanofibre membrane containing collagen I, electrospun directly onto a micro-photoelectroformed fine nickel supporting mesh. GEnC and podocytes grew in monolayers on either side of the insert support or the novel membrane to form a tri-layer model recapitulating the human glomerular capillary in vitro. These models will advance the study of both the physiology of normal glomerular filtration and of its disruption in glomerular disease.

  4. Parietal cells-new perspectives in glomerular disease.

    Science.gov (United States)

    Miesen, Laura; Steenbergen, Eric; Smeets, Bart

    2017-07-01

    In normal glomeruli, parietal epithelial cells (PECs) line the inside of Bowman's capsule and form an inconspicuous sheet of flat epithelial cells in continuity with the proximal tubular epithelial cells (PTECs) at the urinary pole and with the podocytes at the vascular pole. PECs, PTECs and podocytes have a common mesenchymal origin and are the result of divergent differentiation during embryogenesis. Podocytes and PTECs are highly differentiated cells with well-established functions pertaining to the maintenance of the filtration barrier and transport, respectively. For PECs, no specific function other than a structural one has been known until recently. Possible important functions for PECs in the fate of the glomerulus in glomerular disease have now become apparent: (1) PECs may be involved in the replacement of lost podocytes; (2) PECs form the basis of extracapillary proliferative lesions and subsequent sclerosis in glomerular disease. In addition to the acknowledgement that PECs are crucial in glomerular disease, knowledge has been gained regarding the molecular processes driving the phenotypic changes and behavior of PECs. Understanding these molecular processes is important for the development of specific therapeutic approaches aimed at either stimulation of the regenerative function of PECs or inhibition of the pro-sclerotic action of PECs. In this review, we discuss recent advances pertaining to the role of PECs in glomerular regeneration and disease and address the major molecular processes involved.

  5. Glomerular hyperfiltration: definitions, mechanisms and clinical implications.

    Science.gov (United States)

    Helal, Imed; Fick-Brosnahan, Godela M; Reed-Gitomer, Berenice; Schrier, Robert W

    2012-02-21

    Glomerular hyperfiltration is a phenomenon that can occur in various clinical conditions including kidney disease. No single definition of glomerular hyperfiltration has been agreed upon, and the pathophysiological mechanisms, which are likely to vary with the underlying disease, are not well explored. Glomerular hyperfiltration can be caused by afferent arteriolar vasodilation as seen in patients with diabetes or after a high-protein meal, and/or by efferent arteriolar vasoconstriction owing to activation of the renin-angiotensin-aldosterone system, thus leading to glomerular hypertension. Glomerular hypertrophy and increased glomerular pressure might be both a cause and a consequence of renal injury; understanding the renal adaptations to injury is therefore important to prevent further damage. In this Review, we discuss the current concepts of glomerular hyperfiltration and the renal hemodynamic changes associated with this condition. A physiological state of glomerular hyperfiltration occurs during pregnancy and after consumption of high-protein meals. The various diseases that have been associated with glomerular hyperfiltration, either per nephron or per total kidney, include diabetes mellitus, polycystic kidney disease, secondary focal segmental glomerulosclerosis caused by a reduction in renal mass, sickle cell anemia, high altitude renal syndrome and obesity. A better understanding of the mechanisms involved in glomerular hyperfiltration could enable the development of new strategies to prevent progression of kidney disease.

  6. Diadenosine pentaphosphate modulates glomerular arteriolar tone and glomerular filtration rate.

    Science.gov (United States)

    Patzak, A; Carlström, M; Sendeski, M M; Lai, E Y; Liu, Z Z; Sällström, J; Flöge, J; Heintz, B; Jankowski, J; Jankowski, V

    2015-01-01

    Mechanisms and participating substances involved in the reduction of glomerular filtration (GFR) in contrast-induced acute kidney injury (CI-AKI) are still matter of debate. We hypothesized that diadenosine polyphosphates are released by the action of contrast media on tubular cells and may act on glomerular arterioles and reduce GFR. Freshly isolated rat tubules were treated with the contrast medium iodixanol (47 mg iodine per mL) at 37 °C for 20 min. The content of Apn A (n = 3-6) in the supernatant of treated tubules and in the plasma of healthy persons and patients with AKI was analysed using reversed-phase chromatography, affinity chromatography and mass spectrometry. GFR was obtained in conscious mice by inulin clearance. Concentration response curves for Apn A (n = 3-6, 10(-12) -10(-5)  mol L(-1) ) were measured in isolated perfused glomerular arterioles. Iodixanol treatment of tubules significantly increased the concentration of Apn A (n = 3-5) in the supernatant. Ap6 A was below the detection limit. AKI patient shows higher concentrations of Apn A compared to healthy. Application of Ap5 A significantly reduced the GFR in conscious mice. Ap5 A reduced afferent arteriolar diameters, but did not influence efferent arterioles. The constrictor effect on afferent arterioles was strong immediately after application, but weakened with time. Then, non-selective P2 inhibitor suramin blocked the Ap5 A-induced constriction. The data suggest that Ap5 A plays a role in the pathophysiology of CI-AKI. We show a contrast media-induced release of Ap5 A from tubules, which might increase afferent arteriolar resistance and reduce the GFR. © 2014 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

  7. Progression of renal injury toward interstitial inflammation and glomerular sclerosis is dependent on abnormal protein filtration.

    Science.gov (United States)

    Zoja, Carlamaria; Abbate, Mauro; Remuzzi, Giuseppe

    2015-05-01

    Chronic proteinuric renal diseases, independent from the type of the initial insult, have in common a loss of selectivity of the glomerular barrier to protein filtration. Glomerular sclerosis is the progressive lesion affecting the glomerular capillary wall, the primary site at which the protein filtration is abnormally enhanced by disease. Dysfunction of podocytes, that serve to maintain the intact barrier, is a central event in lesion development. However, glomerular injury is signalled to tubular and interstitial structures largely in advance of nephron destruction. Glomerular ultrafiltration of excessive amounts of plasma-derived proteins and associated factors incites tubulointerstitial damage and might amplify an inherent susceptibility of the kidney to become dysfunctional in several disease conditions. Thus, noxious substances in the proteinuric ultrafiltrate promote apoptotic responses and multiple changes in the phenotype of tubule cells with generation of inflammatory and fibrogenic mediators. The severity of tubular interstitial damage has long been recognized to be highly correlated to the degree of deterioration of renal failure even better than glomerular lesions. This review focuses on pathways of tubular injury and apoptosis that in turn promote nephron-by-nephron degeneration and interstitial fibrosis during proteinuria contributing to multifaceted processes of kidney scarring and function loss. © The Author 2014. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

  8. Measurement of glomerular filtration rate

    International Nuclear Information System (INIS)

    D'haene, E.G.M.

    1987-01-01

    Discussed are various methods for measuring the glomerular filtration rate in men. The unsuitability of the creatinine clearance is again emphasized. Based on comparative studies of Fawdry et al, it is stated that using the single-shot single sample methods by using theoretical distribution volumes is the obvious technique. In Dordrecht a program is developed based on the work of Tauxe et al on the analogy of the program for ERPF determination. Some patient studies are demonstrated. The GFR determination has some disadvantages however there are indications that by using the Captopril test the GFR determination is preferred above the ERPF measurement. 11 refs.; 6 figs.; 4 tabs

  9. Histamine type 1-receptor activation by low dose of histamine undermines human glomerular slit diaphragm integrity.

    Science.gov (United States)

    Veglia, Eleonora; Pini, Alessandro; Moggio, Aldo; Grange, Cristina; Premoselli, Federica; Miglio, Gianluca; Tiligada, Katerina; Fantozzi, Roberto; Chazot, Paul L; Rosa, Arianna Carolina

    2016-12-01

    Histamine has been reported to decrease the ultrafiltration coefficient, which inversely correlates with glomerular permselectivity, however the mechanism(s) underling this effect have never been investigated. This study aimed to assess whether histamine could exert a direct detrimental effect on podocyte permeability and the possible involvement of two key proteins for the glomerular slit diaphragm (SD) integrity, zonula occludens-1 (ZO-1) and P-cadherin. The effect of histamine (100 pM-1000nM) on coloured podocytes junctional integrity was evaluated functionally by a transwell assay of monolayer permeability and morphologically by electron microscopy. Histamine receptor (H 1-4 R) presence was evaluated at both mRNA (RT-PCR) and protein (immunofluorescence) levels. The K d and B max values for [ 3 H]mepyramine were determined by saturation binding analysis; IP 1 and cAMP production evoked by histamine were measured by TR-FRET. ZO-1, P-cadherin and vimentin expression was assessed by qRT-PCR and quantitative immunoblotting. Histamine elicited a time- and sigmoidal dose-dependent (maximum effect at 8h, 10nM) increase in podocyte paracellular permeability widening the paracellular spaces. Only H 1 R was predominantly localised to the podocyte membrane. Consistently, histamine elicited a sigmoidal dose-dependent increase in IP 1 , but not in cAMP. Histamine exposure evoked a concentration-dependent reduction in both ZO-1 and P-cadherin and a parallel induction of vimentin mRNA expression with a maximum effect after 6h, and protein expression with a maximum effect after 8h. These effects were prevented by the selective H 1 R antagonist chlorpheniramine. In conclusion, our data demonstrate that histamine, via the H 1 R, modifies SD morphological and functional integrity, in part, by decreasing the expression of ZO-1 and P-cadherin. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Schistosomal glomerular disease (a review

    Directory of Open Access Journals (Sweden)

    Zilton A. Andrade

    1984-12-01

    Full Text Available In this review paper schistosomal glomerulopathy is defined as an immune-complex disease. The disease appears in 12-15 per cent of the individuals with hepatosplenic schistosomiasis. Portal hypertension with collateral circulation helps the by pass of the hepatic clearance process and the parasite antigens can bind to antibodies in the circulation and be trapped in the renal glomerulus. Chronic membranousproliferative glomerulonephritis is the most commom lesion present and the nephrotic syndrome is the usual form of clinical presentation. The disease can be experimentally produced, and schistosomal antigens and antibodies, as well as complement, can be demonstrated in the glomerular lesions. Specific treatment of schistosomiasis does not seem to alter the clinical course of schistosomal nephropathy.A glomerulopatia esquistossomotica e um exemplo de doenca causada por complexos imunes. Ela se manifesta em 12 a 15% dos portadores de forma hepato-eplenica da esquistossomose. A hipertensao porta, com circulacao colateral, facilita a ultrapassagem do filtro hepatico e os antigenos esquistossomoticos podem se acoplar aos anticorpos na circulacao e vir a se depositar nos glomerulos. O tipo histologico mais frequente e a glomerulonefrite cronica membrano-proliferativa, geralmente com sindrome nefrotica. A doenca e passivel de reproducao experimental e os antigenos esquistossomoticos, os anticorpos e fracoes do complemento podem ser demonstrados nas lesoes glomerulares. O tratamento especifico da esquistossomose nao mostrou ate o momento a capacidade de alterar o curso da nefropatia.

  11. Soluble CD40 ligand directly alters glomerular permeability and may act as a circulating permeability factor in FSGS.

    Directory of Open Access Journals (Sweden)

    Sophie Doublier

    Full Text Available CD40/CD40 ligand (CD40L dyad, a co-stimulatory bi-molecular complex involved in the adaptive immune response, has also potent pro-inflammatory actions in haematopoietic and non-haematopoietic cells. We describe here a novel role for soluble CD40L (sCD40L as modifier of glomerular permselectivity directly acting on glomerular epithelial cells (GECs. We found that stimulation of CD40, constitutively expressed on GEC cell membrane, by the sCD40L rapidly induced redistribution and loss of nephrin in GECs, and increased albumin permeability in isolated rat glomeruli. Pre-treatment with inhibitors of CD40-CD40L interaction completely prevented these effects. Furthermore, in vivo injection of sCD40L induced a significant reduction of nephrin and podocin expression in mouse glomeruli, although no significant increase of urine protein/creatinine ratio was observed after in vivo injection. The same effects were induced by plasma factors partially purified from post-transplant plasma exchange eluates of patients with focal segmental glomerulosclerosis (FSGS, and were blocked by CD40-CD40L inhibitors. Moreover, 17 and 34 kDa sCD40L isoforms were detected in the same plasmapheresis eluates by Western blotting. Finally, the levels of sCD40Lwere significantly increased in serum of children both with steroid-sensitive and steroid-resistant nephrotic syndrome (NS, and in adult patients with biopsy-proven FSGS, compared to healthy subjects, but neither in children with congenital NS nor in patients with membranous nephropathy. Our results demonstrate that sCD40L directly modifies nephrin and podocin distribution in GECs. Moreover, they suggest that sCD40L contained in plasmapheresis eluates from FSGS patients with post-transplant recurrence may contribute, presumably cooperating with other mediators, to FSGS pathogenesis by modulating glomerular permeability.

  12. Haematuria as a risk factor for chronic kidney disease progression in glomerular diseases: A review.

    Science.gov (United States)

    Moreno, Juan Antonio; Yuste, Claudia; Gutiérrez, Eduardo; Sevillano, Ángel M; Rubio-Navarro, Alfonso; Amaro-Villalobos, Juan Manuel; Praga, Manuel; Egido, Jesús

    2016-04-01

    Haematuria has long been considered to be a benign condition associated with glomerular diseases. However, new evidences suggest that haematuria has a pathogenic role in promoting kidney disease progression. An increased risk for end-stage renal disease has been reported in adolescents and young adults with persistent microscopic haematuria. A persistent impairment of renal function has been also reported following macroscopic haematuria-associated acute kidney injury in immunoglobulin A nephropathy. Haematuria-induced renal damage has been related to oxidant, cytotoxic and inflammatory effects induced by haemoglobin or haem released from red blood cells. The pathophysiological origin of haematuria may be due to a more fragile and easily ruptured glomerular filtration barrier, as reported in several glomerular diseases. In this review we describe a number of the key issues associated with the epidemiology and pathogenesis of haematuria-associated diseases, provide an update of recent knowledge on the role of haematuria on renal function outcome and discuss specific therapeutic approaches in this setting. KEY SUMMARY POINTS: 1. Glomerular haematuria is a common observation in a number of renal diseases that may lead to persistent renal injury. 2. Haematuria in children differs from that in adults in specific aspects, particularly in the frequency of glomerular diseases and renal disease outcome. 3. Regular follow-up of renal function in children with isolated microhaematuria may be recommended.

  13. Synthesis and analysis of novel polymers with high permselectivity and permeability in gas separation applications. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Koros, W.J.; Paul, D.R.

    1995-05-01

    During the three years of support under this grant, ten novel polymer structures have been synthesized and characterized in detail in terms of sorption and transport properties to test the hypotheses on strategies to develop advanced materials for gas separation membranes. The extremely important O{sub 2}/N{sub 2} and CO{sub 2}/CH{sub 4} systems have been the focus of this work. Data for permeabilities and permselectivities for O{sub 2}/N{sub 2} and CO{sub 2}/CH{sub 4} at 35 C at approximately 2 atm feed pressure for O{sub 2} and N{sub 2} and 10 atm for CO{sub 2} and CH{sub 4} are reported in two tables and will be discussed in two parts, one related to each of the groups of structures in these two tables. For the sake of efficiency, the author will only consider the O{sub 2}/N{sub 2} data; however, similar trends apply for the CO{sub 2}/CH{sub 4} system as well. This gas pair is useful, since solubility selectivity effects are generally of much smaller importance than for the CO{sub 2}/CH{sub 4} pair, so even without detailed solubility and diffusivity data, mobility selectivity based arguments tend to be adequate.

  14. Documentation of renal glomerular and tubular impairment and glomerular hyperfiltration in multitransfused patients with beta thalassemia.

    Science.gov (United States)

    Deveci, Burak; Kurtoglu, Aysegul; Kurtoglu, Erdal; Salim, Ozan; Toptas, Tayfur

    2016-02-01

    Urinary albumin to creatinine (ACR) and beta2 microglobulin to creatinine ratios (BCR) are the surrogate and robust markers of renal glomerulopathy and tubulopathy, respectively. These markers predict short-term renal deterioration and mortality in various conditions. We aimed to assess the frequency and predictors of glomerular and tubular defects, renal impairment, and hyperfiltration in 96 adult patients with beta thalassemia intermedia and major. ACR > 300 mg/g creatinine and BCR > 300 μg/g creatinine were used to define the renal glomerular and tubular damages, respectively. Glomerular filtration rate (eGFRcreat) was estimated according to 2009 the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. Decreased eGFRcreat was defined as less than 60 mL/min per 1.73 m(2). Renal glomerular and/or tubular defects were observed in about 68.8 % of all patients. Forty percent of patients had glomerular hyperfiltration. None of the patients had a decreased eGFRcreat. T2* value ≤20 msec on cardiac magnetic resonance (cMR) was the only independent predictor of glomerular damage (p = 0.013). Use of alendronate was associated with less renal tubular damage (p = 0.007). Female gender and previous history of splenectomy were the independent predictors of glomerular hyperfiltration in multivariate analysis (p glomerular damage is frequent in adult patients with thalassemia intermedia and major. T2* value on cMR was the only independent predictor of glomerular damage. However, since we did not explore all the parameters of iron, it is not possible to draw a definite conclusion about the association of cMR and glomerular damage. There is no association with cardiac iron overload/accumulation and tubular damage or hyperfiltration.

  15. Glomerular sieving of high molecular weight proteins in proteinuric rats

    International Nuclear Information System (INIS)

    Bertolatus, J.A.; Abuyousef, M.; Hunsicker, L.G.

    1987-01-01

    To characterize the permeability of the glomerular capillary wall to high molecular weight proteins in normal and proteinuric rats, we determined the glomerular sieving coefficients (GSC) of radioiodinated marker proteins of known size and charge by means of a paired label, tissue accumulation method previously validated in this laboratory. In one group of rats (Series A) the GSCs of 125 I-anionic IgG (aIgG-molecular weight [mol wt] 150,000, pI 4.9) and 131 I-neutral IgG (nIgG-pI 7.4 to 7.6) were measured simultaneously. In Series B, the GSC of a second anionic marker, 131 I-human ceruloplasmin (Crp-mol wt 137,000, pI 4.9) was compared to that of 125 I-nIgG. As in the previous report, the labeled proteins were not degraded or deiodinated during the 20 minute clearance period for GSC determination. Within Series A and B, three subgroups of rats were studied: control saline-infused rats, rats made acutely proteinuric by infusion of the polycation hexadimethrine (HDM), and rats with chronic doxorubicin (Adriamycin-Adria) nephrosis. In the control rats, GSCs for the anionic markers aIgG (Series A) or Crp (Series B) were significantly greater than that of nIgG (both series). These large proteins crossed the filtration barrier by a different pathway from that available to smaller neutral molecules the size of albumin, which in our previous study had a much higher GSC than a native, anionic albumin marker. In a third group of control rats only (Series C), the GSCs of native anionic bovine albumin (BSA) and nIgG were compared directly. The GSC of BSA (0.0029) was only slightly larger than the GSC of nIgG (0.0025), indicating that most of the native albumin crosses the glomerular capillary wall via a nonselective pathway similar to that available to nIgG. The results in the control groups are compatible with recently-described heteroporous models of glomerular size selectivity

  16. Crosstalk in glomerular injury and repair

    DEFF Research Database (Denmark)

    Dimke, Henrik; Maezawa, Yoshiro; Quaggin, Susan E

    2015-01-01

    the capillary loops and lie in close contact with mesangial cells. Podocytes are connected by specialized intercellular junctions known as slit diaphragms and separated from the endothelial compartment by the glomerular basement membrane. In order for this highly specialized structure to function, cross...

  17. Glomerular Lesions in Proteinuric Miniature Schnauzer Dogs.

    Science.gov (United States)

    Furrow, E; Lees, G E; Brown, C A; Cianciolo, R E

    2017-05-01

    Miniature Schnauzer dogs are predisposed to idiopathic hypertriglyerceridemia, which increases risk for diseases such as pancreatitis and gallbladder mucocele. Recently, elevated triglyceride concentrations have been associated with proteinuria in this breed, although it is difficult to determine which abnormality is primary. Retrospective review of renal tissue from 27 proteinuric Miniature Schnauzers revealed that 20 dogs had ultrastructural evidence of osmophilic globules consistent with lipid in glomerular tufts. Seven of these dogs had lipid thromboemboli in glomerular capillary loops that distorted their shape and compressed circulating erythrocytes. Triglyceride concentrations were reported in 6 of these 7 dogs, and all were hypertriglyceridemic. In addition, glomerular lipidosis (defined as accumulation of foam cells within peripheral capillary loops) was identified in a single dog. The remaining 12 dogs had smaller amounts of lipid that could only be identified ultrastructurally. Neither signalment data nor clinicopathologic parameters (serum albumin, serum creatinine, urine protein-to-creatinine ratio, and blood pressure) differed among the various types of lipid lesions. During the time course of this study, all dogs diagnosed with glomerular lipid thromboemboli were Miniature Schnauzers, underscoring the importance of recognizing these clear spaces within capillary loops as lipid.

  18. Glomerular latency coding in artificial olfaction

    Directory of Open Access Journals (Sweden)

    Jaber eAl Yamani

    2012-01-01

    Full Text Available Sensory perception results from the way sensory information is subsequently transformed in the brain. Olfaction is a typical example in which odor representations undergo considerable changes as they pass from olfactory receptor neurons (ORNs to second-order neurons. First, many ORNs expressing the same receptor protein yet presenting heterogeneous dose-response properties converge onto individually identifiable glomeruli. Second, onset latency of glomerular activation is believed to play a role in encoding odor quality and quantity in the context of fast information processing. Taking inspiration from the olfactory pathway, we designed a simple yet robust glomerular latency coding scheme for processing gas sensor data. The proposed bio-inspired approach was evaluated using an in-house Sn02 sensor array. Glomerular convergence was achieved by noting the possible analogy between receptor protein expressed in ORNs and metal catalyst used across the fabricated gas sensor array. Ion implantation was another technique used to account both for sensor heterogeneity and enhanced sensitivity. The response of the gas sensor array was mapped into glomerular latency patterns, whose rank order is concentration-invariant. Gas recognition was achieved by simply looking for a match within a library of spatio-temporal spike fingerprints. Because of its simplicity, this approach enables the integration of sensing and processing onto a single-chip.

  19. Determination of glomerular filtration rate with radionuclide ...

    African Journals Online (AJOL)

    Mulligan JS, Blue PW, Hasbargen JA. Methods for measuring GFR with technetium-99m-OTPA: an analysis of several common methods. J Nucl Med. 1990; 31: 1211-1219. 4. Jackson JH. Blue PW. Ghaed N. Glomerular filtration rate determined in conjunction with routine renal scanning. Radiology 1985; 154: 203-205. 5.

  20. A novel water perm-selective membrane dual-type reactor concept for Fischer-Tropsch synthesis of GTL (gas to liquid) technology

    International Nuclear Information System (INIS)

    Rahimpour, M.R.; Mirvakili, A.; Paymooni, K.

    2011-01-01

    The present study proposes a novel configuration of Fischer-Tropsch synthesis (FTS) reactors in which a fixed-bed water perm-selective membrane reactor is followed by a fluidized-bed hydrogen perm-selective membrane reactor. This novel concept which has been named fixed-bed membrane reactor followed by fluidized-bed membrane reactor (FMFMDR) produces gasoline from synthesis gas. The walls of the tubes of a fixed-bed reactor (water-cooled reactor) of FMFMDR configuration are coated by a high water perm-selective membrane layer. In this new configuration, two membrane reactors instead of one membrane reactor are developed for FTS reactions. In other words, two different membrane layers are used. In order to investigate the performance of FMFMDR, a one-dimensional heterogeneous model is taken into consideration. The simulation results of three schemes named fluidized-bed membrane dual-type reactor (FMDR), FMFMDR and conventional fixed-bed reactor (CR) are presented. They have been compared in terms of temperature, gasoline and CO 2 yields, H 2 and CO conversions and the water permeation rate through the membrane layer. Results show that the gasoline yield in FMFMDR is higher than the one in FMDR. The FMFMDR configuration not only decreases the undesired product such as CO 2 but also produces more gasoline. -- Research highlights: → The application of H-SOD membrane layer in FTS reactors. → Approximate 7.5% and 37% increase in the gasoline yield in terms of [g/g feed x 100] in comparison with FMDR and CR, respectively. → A remarkable decrease in CO 2 emission to the environment. → A good configuration mainly due to reduction in catalysts sintering as a result of in situ water removal.

  1. Simplified method of radionuclide determination of glomerular filtration

    International Nuclear Information System (INIS)

    Butsev, Yu.A.

    1991-01-01

    Glomerular filtration is one of the chief components of renal function. The biochemical methods of its determination (clearance of insulin and endogeneous creatinine) have a number of shortcomings. The use of labelled glomerulotropic agents simplifies methods of the determination of glomerular filtration. A formula and a table of a glomerular filtration value per 1 kg of body mass were calculated

  2. Comparative aspects of glomerular filtration in vertebrates.

    Science.gov (United States)

    Yokota, S D; Benyajati, S; Dantzler, W H

    1985-01-01

    Glomerular ultrafiltration of the plasma is a fundamental component of vertebrate renal function. The importance of the glomerulus is reflected by its near-universal presence and great elaboration among the vertebrates. Although the general structural features and functional properties of the glomerulus appear to be largely similar among diverse groups, there exists considerable variation in the magnitude of the rate of filtration. The kidney is the primary vertebrate organ responsible for water and metabolic waste excretion, and glomerular filtration plays an important role in these functions. Therefore, the magnitude of the GFR appears to be influenced primarily by the rates of water influx and metabolism. Major phylogenetic differences in morphological, physiological and metabolic design have a decisive impact on the magnitude of the GFR. The endothermic classes, with more numerous glomeruli, high metabolic rates, and high ultrafiltration pressures, have proportionately higher rates of glomerular filtration than the ectothermic groups. As a group, the reptiles, with presumably the lowest rates of water influx, exhibit the lowest GFRs. Within each class, there are trends toward species with greater access to free water having higher GFRs (e.g. fresh water vs. marine; mesic vs. xeric. The clearest examples exist for the teleosts, with marine forms having lower GFRs than their fresh water relatives. The coupling of the GFR to environmental influences is also demonstrated by the response of the animal to environmentally imposed perturbations, such as dehydration. In terrestrial animals during dehydration, reductions in the rate of glomerular filtration occur reducing the rate of urinary water loss. And increases in GFR appears to be important in the rapid elimination of water loads in nonmammalian vertebrates. This short-term modulation of the GFR occurs by either changing glomerular plasma flow or glomerular capillary hydrostatic pressure, or both. In addition

  3. Glomerular filtration into the subpodocyte space is highly restricted under physiological perfusion conditions.

    Science.gov (United States)

    Neal, Christopher R; Muston, P Robert; Njegovan, David; Verrill, Rebecca; Harper, Steven J; Deen, William M; Bates, David O

    2007-12-01

    Production of urine is initiated by fluid and solute flux across the glomerular filtration barrier. Recent ultrastructural studies have shown that under extreme conditions of no filtration, or very high filtration, a restriction to flow is predicted in a space underneath the podocyte cell body or its processes, the subpodocyte space (SPS). The SPS covered up to two-thirds of the glomerular filtration barrier (GFB) surface. The magnitude of this restriction to flow suggested that it might be unlikely that filtration into and flow through the SPS would contribute significantly to total flow across the entire GFB under these conditions. To determine whether the SPS has similar properties under normal physiological conditions, we have carried out further three-dimensional reconstruction of rat glomeruli perfused at physiologically normal hydrostatic and colloid osmotic pressures. These reconstructions show that the sub-podocyte space is even more restricted under these conditions, with a mean height of the SPS of 0.34 microm, mean pathlength of 6.7 +/- 1.4 mum, a mean width of the SPS exit pore of 0.15 +/- 0.05 microm, and length of 0.25 +/- 0.05 microm. Mathematical modeling of this SPS based on a circular flow model predicts that the resistance of these dimensions is 2.47 times that of the glomerular filtration barrier and exquisitely sensitive to changes in the dimensions of the SPS exit pore (SEP), indicating that the SEP could be the principal regulator of the extravascular pressure in the SPS. This suggests a physiological role of the podocyte in the regulation of glomerular fluid flux across most of the GFB.

  4. Amperometric detection of glucose in fruit juices with polypyrrole-based biosensor with an integrated permselective layer for exclusion of interferences.

    Science.gov (United States)

    Ayenimo, Joseph G; Adeloju, Samuel B

    2017-08-15

    A novel polypyrrole (PPy)-based bilayer amperometric glucose biosensor integrated with a permselective layer has been developed for detection of glucose in the presence of interferences. It comprises of a PPy-GOx film grown, in the absence of electrolyte, as an inner layer, and a permselective PPy-Cl film as an outer layer. The PPy-GOx/PPy-Cl bilayer biosensor was effective in rejecting 98% of ascorbic acid and 100% of glycine, glutamic acid and uric acid. With an outer layer thickness of 6.6nm, the bilayer biosensor gave nearly identical glucose response to that of a single layer PPy-GOx biosensor. The biosensor also exhibited good reproducibility (1.9% rsd, n=10), high stability (more than 2months), wide linear range (0.5-24mM), low K m (8.4mM), high I max (77.2μAcm -2 ), low detection limit (26.9μM) and good sensitivity (3.5μAcm -2 mM -1 ). The bilayer biosensor was successfully employed for glucose determination in various fruit juices. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Aberrant glomerular filtration of urokinase-plasminogen activator in nephrotic syndrome leads to amiloride-sensitive plasminogen activation in urine

    DEFF Research Database (Denmark)

    Stæhr, Mette; Buhl, Kristian Bergholt; Andersen, René F

    2015-01-01

    In nephrotic syndrome, aberrant glomerular filtration of plasminogen and conversion to active plasmin in pre-urine is thought to activate proteolytically ENaC and contribute to sodium retention and edema. The ENaC blocker amiloride is an off-target inhibitor of urokinase-type plasminogen activator...... with aberrant filtration of uPA across the injured glomerular barrier. Amiloride inhibits urine uPA activity which attenuates plasminogen activation and urine protease activity in vivo. Urine uPA is a relevant target for amiloride in vivo....

  6. Paradoxical glomerular filtration of carbon nanotubes.

    Science.gov (United States)

    Ruggiero, Alessandro; Villa, Carlos H; Bander, Evan; Rey, Diego A; Bergkvist, Magnus; Batt, Carl A; Manova-Todorova, Katia; Deen, William M; Scheinberg, David A; McDevitt, Michael R

    2010-07-06

    The molecular weight cutoff for glomerular filtration is thought to be 30-50 kDa. Here we report rapid and efficient filtration of molecules 10-20 times that mass and a model for the mechanism of this filtration. We conducted multimodal imaging studies in mice to investigate renal clearance of a single-walled carbon nanotube (SWCNT) construct covalently appended with ligands allowing simultaneous dynamic positron emission tomography, near-infrared fluorescence imaging, and microscopy. These SWCNTs have a length distribution ranging from 100 to 500 nm. The average length was determined to be 200-300 nm, which would yield a functionalized construct with a molecular weight of approximately 350-500 kDa. The construct was rapidly (t(1/2) approximately 6 min) renally cleared intact by glomerular filtration, with partial tubular reabsorption and transient translocation into the proximal tubular cell nuclei. Directional absorption was confirmed in vitro using polarized renal cells. Active secretion via transporters was not involved. Mathematical modeling of the rotational diffusivity showed the tendency of flow to orient SWCNTs of this size to allow clearance via the glomerular pores. Surprisingly, these results raise questions about the rules for renal filtration, given that these large molecules (with aspect ratios ranging from 100:1 to 500:1) were cleared similarly to small molecules. SWCNTs and other novel nanomaterials are being actively investigated for potential biomedical applications, and these observations-that high aspect ratio as well as large molecular size have an impact on glomerular filtration-will allow the design of novel nanoscale-based therapeutics with unusual pharmacologic characteristics.

  7. METHODICAL BASES OF ESTIMATION GLOMERULAR FILTRATION RATE IN UROLOGICAL PRACTICE

    Directory of Open Access Journals (Sweden)

    M. M. Batiushin

    2017-01-01

    Full Text Available The article presents a review of methodological issues of estimation of glomerular filtration rate in urologic practice. Author examine the current international and national recommendations, in particular by KDIGO, the recommendations of the scientific society of nephrologists of Russia, Association of urologists of Russia, the results of comparative analysis of different methods of assessing glomerular filtration rate. It is shown that the currently calculated methods of assessment of glomerular filtration rate have advantages over technique of clearance. The advantages and disadvantages of methods for calculating glomerular filtration rate by the formula of Cockcroft-Gault and MDRD. The author lists the pathological conditions in urological practice, in which there is a need to assess glomerular filtration rate, given nomograms and links to online calculators for quick and easy calculation of glomerular filtration rate.

  8. The effect of penbutolol on glomerular filtration

    International Nuclear Information System (INIS)

    Meyer, B.H.; Muller, F.O.; Lotter, M.G.; Iturralde, M.P.; Grigoleit, H.-G.

    1981-01-01

    Penbutolol, a new β-adrenoceptor blocker, was found to increase the glomerular filtration rate (GFR) significantly (16%) relative to placebo when administered orally in a dose of 40 mg daily for 7 consecutive days to healthy males. Measurements were performed after the seventh dose. In contrast, a single acute intravenous dose of penbutolol 4 mg did not influence the GFR, which was determined by means of a gamma counter after intravenous injection of technetium-99m diethylenetriamine-penta-acetic acid. Since penbutolol possesses moderate β-adrenomimetic activity, it is postulated that the observed increase in the GFR after oral penbutolol could be due to increased cardiac output at rest

  9. Glomerular development--shaping the multi-cellular filtration unit.

    Science.gov (United States)

    Schell, C; Wanner, N; Huber, T B

    2014-12-01

    The glomerulus represents a highly structured filtration unit, composed of glomerular endothelial cells, mesangial cells, podocytes and parietal epithelial cells. During glomerulogenesis an intricate network of signaling pathways involving transcription factors, secreted factors and cell-cell communication is required to guarantee accurate evolvement of a functional, complex 3-dimensional glomerular architecture. Here, we want to provide an overview on the critical steps and relevant signaling cascades of glomerular development. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  10. Synthesis of a Fluorine-Containing Cis-Cisoidal One-Handed Helical Polyphenylacetylene and Application of Highly Selective Photocyclic Aromatization Product on Oxygen Permselective Membrane.

    Science.gov (United States)

    Zang, Yu; Yin, Guanwu; Aoki, Toshiki; Teraguchi, Masahiro; Kaneko, Takashi; Ma, Liqun; Jia, Hongge

    2015-08-01

    A novel phenylacetylene monomer having a perfluorinated alkyl group (M-F) was synthesized and polymerized in a chiral catalytic system to yield a one-handed helical polymer. The ability and efficiency of the chiral induction of the fluorine-containing monomer in the helix-sense-selective polymerization (HSSP) was much higher than those of a monomer having the corresponding alkyl group (M-H) we reported before. The resulting polymer showed cis-cisoidal one-handed helical conformation, and was suitable for highly selective photocyclic aromatization (SCAT) to give a 2D surface modifier (). Oxygen permselectivity through a base polymer membrane was highly enhanced from 1.83 to 2.36 by adding a small amount (1-5 wt%) of the 2D surface modifier . The improvement was thought to be caused by improvement of solution selectivity on the membrane surface which the 2D surface modifier effectively covered. © 2015 Wiley Periodicals, Inc.

  11. Development of nickel membranes deposited on ceramic materials by electroless plating: studies of the hydrogen perm-selectivity properties at elevated temperatures

    International Nuclear Information System (INIS)

    Amer, J.

    2008-09-01

    The main objective of this work was to synthesize nickel based membranes by electroless plating on materials such as alumina-α, alumina-γ and zirconia with various textures and to determine their hydrogen perm-selectivity at high temperatures. The synthesis of metal films of high purity (≥ 99% mass Ni) resulting from the choice of hydrazine with its dual role of reducing and complexing agent has revealed that the diameter of pores on the surface support has an impact on the quality of metal adherence. The various contributions of hydrogen transport through these composite membranes at low temperatures (Knudsen and surface diffusion) and at high temperatures (Knudsen and activated diffusion) was established. At its implementation in a membrane reactor (reaction of propane dehydrogenation), the layer of nickel showed a very good resistance to coking. (author)

  12. HUMAN GLOMERULAR VOLUME QUANTIFICATIONDURING THE AGING PROCESS

    Directory of Open Access Journals (Sweden)

    Dejan Zdravković

    2004-12-01

    Full Text Available Kidney function is directly related to the changes of renal tissue, especially glomeruli, which is particularly distinct during the aging process. The impossibility of kidney function substitution points to the need for glomerular morphologic and functional characteristics estimation during the aging process.Human cadaveric kidney tissue samples were used as material during research. Age of cadavers ranged from 20 to 70 years and they were classified according to the scheme: I (20–29; II (30–39; III (40–49; IV (50–59; V (60–69 i VI (older than 70. After the routine histologic preparation of the renal tissue the slices were analized stereologicaly under the light microscope with projection screen (Reichert Visopan with 40 x lens magnification. M42 test system was used and 100, by unbased method selected glomeruli, were analyzed.Average glomerular capillary network volume shows significant increase (p< 0,001 as far as to the age of 50 years in regard to the age of 20 to 29 years. This parameter shows insignificant decrease after the age of 50 until the age of 70 years. This decrease was significant after the age of 70 years in regard to the period of the 20 to 29 (p< 0,05 and the period of 40 to 49 years (p<0,01.

  13. Glomerular Filtration Rate is Unchanged By Ultramarathon.

    Science.gov (United States)

    Wołyniec, Wojciech; Ratkowski, Wojciech; Kasprowicz, Katarzyna; Jastrzębski, Zbigniew; Małgorzewicz, Sylwia; Witek, Konrad; Grzywacz, Tomasz; Żmijewski, Piotr; Renke, Marcin

    2017-12-27

    Acute kidney injury (AKI) is reported as a common complication of marathon and ultramarathon running. In previous studies AKI was diagnosed on the basis of the creatinine level in serum and estimated glomerular filtration rate (eGFR). In the present study we calculated eGFR and also measured creatinine clearance after every 25 km of a 100 km run. 20 healthy, amateur runners (males, mean age 40.75 ± 7.15 years, mean weight 76.87 ± 8.39 kg) took part in a 100 km run on a track. Blood and urine were collected before the run, after every 25 km and 12 hours after the run. 17 runners completed the study. There was increase in creatinine, urea and uric acid observed after 100 km (p AKIN) criteria of AKI. The eGFR according to the MDRD (modification of diet in renal disease), CKD-EPI (chronic kidney disease epidemiology collaboration) and Cockcroft-Gault formulas was significantly decreased after the run (p < 0.05). Otherwise, creatinine clearance calculated from creatinine level in both serum and urine remained stable. In contrast to the majority of previous studies, we did not observe any decrease in the kidney function during an ultramarathon. In this study the creatinine clearance, which is the best routine laboratory method to determine glomerular filtration rate was used. There is no evidence that long running is harmful for kidney.

  14. Important clinical and laboratory correlates of glomerular filtration ...

    African Journals Online (AJOL)

    Background: Renal impairment is routinely assessed using the estimated glomerular filtration rate (eGFR) and it may be helpful to obtain certain clinical or laboratory markers, which show relationship with glomerular filtration rate (GFR) in sickle cell disease (SCD). Aim: To assess the relationship between important clinical ...

  15. Glomerular disease and acute kidney injury in Sudan ...

    African Journals Online (AJOL)

    Age at presentation but not baseline renal function by estimated glomerular filtration rate (eGFR), was associated with the likelihood of having residual chronic kidney disease following an episode of AKI. Conclusions. The data suggested differences in the pattern of intrinsic renal/glomerular disease leading to AKI to those ...

  16. Permselectivity of the liver blood-lymph (ascitic fluid) barrier to macromolecules in decompensated cirrhosis: relation to calculated pore-size

    DEFF Research Database (Denmark)

    Henriksen, Jens Henrik Sahl

    1983-01-01

    in plasma and ascitic fluid from 13 cirrhotic patients. As previously substantiated in patients with cirrhosis, the ascitic fluid/plasma concentration ratio (R) of a protein is proportional to the transport rate from blood to lymph (ascitic fluid). Mean Ralb = 0.28 and RIgG = 0.29 were identical......, but significantly higher than, RIgM = 0.18 (P less than 0.01). Ralb was directly correlated to RIgG (r = 0.97, P less than 0.001) and to RIgM (r = 0.78, P less than 0.005). Mean RIgG/Ralb = 1.03, which expresses the relative flux rates between IgG and albumin, was significantly above the ratio between the free...... diffusion coefficients (DIgG/Dalb = 0.64, P less than 0.01). Mean RIgM/Ralb = 0.61 was significantly above DIgM/Dalb = 0.39 (P less than 0.05) and significantly below unity (P less than 0.01). The results are best explained by filtration as the dominant mechanism of the liver blood-lymph (ascitic fluid...

  17. Impact of age on glomerular filtration estimates.

    Science.gov (United States)

    Douville, Pierre; Martel, Ariane R; Talbot, Jean; Desmeules, Simon; Langlois, Serge; Agharazii, Mohsen

    2009-01-01

    Glomerular filtration decreases progressively with age in adults. Predictive equation should have proper modelling to adequately account for normal senescence. Corrected 24-h creatinine clearances (CCLs) were measured in a cohort of 773 outpatients from 18 to 90 years old. Multiple linear regression was used to model the effect of age on glomerular filtration. Comparisons were made with the simplified MDRD and the MAYO equations. Impact of the derived equation was tested in a second cohort of 7551 patients with normal serum creatinine. While all equations show declining function with age, our results suggest that the GFR reduction is progressive after the age of 30 and continue to decline steadily after the age of 60. This leads to a convex curve in the multiple regression analysis that is best fitted by an equation including the quadratic term (age(2)). In contrast, the MDRD equation produces a faster decrease in early adulthood and a flatter curve after the age of 60 while the MAYO equation produces a more linear effect. MDRD results in the normal range are lower than those estimated by the MAYO equation. These equations, as applied on an independent cohort of 7551 normal outpatients from 18 to 102 years, produce different profile of evolution of GFR with age. Inclusion of a quadratic term for age in the formula estimating GFR results in better modelling of the natural decline of renal function associated with ageing. Furthermore, as GFR steadily declines after the age of 30, a single cut-off value of GFR normality for all ages leads to underdiagnosis of young adults and over diagnosis of elderly individuals. Guidelines should take into account the observed reduction of kidney function with age in normal population for optimal evaluation of eGFR.

  18. Gallium 67 scintigraphy in glomerular disease

    Energy Technology Data Exchange (ETDEWEB)

    Bakir, A.A.; Lopez-Majano, V.; Levy, P.S.; Rhee, H.L.; Dunea, G.

    1988-12-01

    To evaluate the diagnostic usefulness of gallium 67 scintigraphy in glomerular disease, 45 patients with various glomerulopathies, excluding lupus nephritis and renal vasculitis, were studied. Persistent renal visualization 48 hours after the gallium injection, a positive scintigram, was graded as + (less than), ++ (equal to), and +++ (greater than) the hepatic uptake. Positive scintigrams were seen in ten of 16 cases of focal segmental glomerulosclerosis, six of 11 cases of proliferative glomerulonephritis, and one case of minimal change, and one of two cases of membranous nephropathy; also in three of six cases of sickle glomerulopathy, two cases of diabetic neuropathy, one of two cases of amyloidosis, and one case of mild chronic allograft rejection. The 25 patients with positive scans were younger than the 20 with negative scans (31 +/- 12 v 42 +/- 17 years; P less than 0.01), and exhibited greater proteinuria (8.19 +/- 7.96 v 2.9 +/- 2.3 S/d; P less than 0.01) and lower serum creatinine values (2 +/- 2 v 4.1 +/- 2.8 mg/dL; P less than 0.01). The amount of proteinuria correlated directly with the intensity grade of the gallium image (P less than 0.02), but there was no correlation between the biopsy diagnosis and the outcome of the gallium scan. It was concluded that gallium scintigraphy is not useful in the differential diagnosis of the glomerular diseases under discussion. Younger patients with good renal function and heavy proteinuria are likely to have a positive renal scintigram regardless of the underlying glomerulopathy.

  19. Improved metabolic control does not alter the charge-dependent glomerular filtration of albumin in uncomplicated type 1 (insulin-dependent) diabetes

    DEFF Research Database (Denmark)

    Kverneland, A; Welinder, B; Feldt-Rasmussen, B

    1988-01-01

    . It was, however, unaffected by 12 weeks of improved metabolic control with a mean decline in HbA1c of 1.9% in seven patients. We conclude that the increased electronegative charge of the glomerular filtration barrier observed in uncomplicated diabetes is related to long term metabolic control...

  20. Dynamics of intrarenal pressures and glomerular filtration rate after acetazolamide

    DEFF Research Database (Denmark)

    Leyssac, P P; Karlsen, F M; Skøtt, O

    1991-01-01

    The dynamics of intrarenal pressures, early distal tubular fluid conductivity (EDC), and renal flood flow (RBF) were studied in rats given acetazolamide (ACZ), an inhibitor of proximal reabsorption. Glomerular filtration rate (GFR) and end-proximal flow were estimated by clearances of 51Cr......-EDTA and lithium. Proximal tubular pressure (Pprox) increased initially by 1.7 +/- 0.1 mmHg after ACZ, causing a decrease in the hydrostatic pressure difference across the glomerular membrane (delta P). EDC increased, and then RBF, glomerular capillary pressure (Pgc), Pprox, and star vessel pressures (Psv) dropped...

  1. Physiopathology glomerular hyperfiltration in diabetes. Part 1

    Directory of Open Access Journals (Sweden)

    Claudio A. Mascheroni

    2014-09-01

    Full Text Available Glomerular hyperfiltration (HF in diabetic kidney disease is a complex hemodynamic phenomenon which occurs in early stages of the disease’s progress and probably has negative influences, regarding the progression to the occurrence of microalbuminuria and the progress of evident diabetic nephropathy (DN. Factors involved in its physiopathology are numerous, they include: diabetic biochemical environment and several humoral factors like nitric oxide, prostaglandins, renin-angiotensin-aldosterone system, atrial natriuretic peptide, reactive oxygen species, other humoral and growth factors. These factors cause or enhance the vasodilatation of the afferent arteriole (AA. Factors with vasoconstriction function over the efferent arteriole, all considered primary vascular factors. However, these factors cannot explain other observed alterations and they constitute primary tubular abnormalities such as the increased reabsorption at the proximal tubule, probably conditioned by kidney growth in DBT and by the overexpression of the SGLT2 cotransporter. This higher proximal reabsorption would produce a lower arrival of solutes to the macula densa (MD. This would be incompatible with an action of the tubuloglomerular balance system, but it would be compatible with an action performed by the tubuloglomerular feedback system (TGFB that senses the decrease of the ClNa concentration at the MD. Also deactivating the TGFB and causing vasodilatation of the AA, resulting in an increase of glomerular filtration (GF and renal plasma flow (RPF, characteristic of the HF process. These two processes (vascular and tubular could act in synergy or simultaneously, depending on the metabolic and progressing conditions of the diabetic kidney disease. Similar mechanisms could explain the salt paradox, whereby a lowsalt diet would exacerbate the HF phenomenon and a high-salt diet would decrease the GF and the RPF, which could result in unexpected clinical implications. The

  2. Permeability of peritoneal and glomerular capillaries: what are the differences according to pore theory?

    Science.gov (United States)

    Rippe, Bengt; Davies, Simon

    2011-01-01

    Pore and fiber-matrix theory can both be used to model the peritoneal and glomerular filtration barriers in an attempt to shed light on their differing structure-function relationships. The glomerular filtration barrier (GFB) is structurally more specialized, morphologically complex, and also highly dynamic; but paradoxically, because of its uniformity, it conforms more closely to the predictions of pore theory than does the peritoneum, and it in fact resembles a more simple synthetic membrane. Compared with the peritoneal capillary wall, the GFB has no transcellular "third" pores (aquaporins), and it is far less leaky and more size-selective to proteins, mainly as a result of having far fewer "large" pores. It does have charge-selective properties, although these are considered much less important in excluding albumin than was once thought, and it is also able to select polymers according to their shape and flexibility. Even this property might reflect the relative uniformity of the GFB, which has a high diffusion area and short diffusion distances, compared with the peritoneal barrier, which behaves more like a gel filtration column. Furthermore, the length of the diffusion path across the peritoneal membrane is much greater for small solutes, given the relatively high ultrafiltration coefficient for that membrane compared with the GFB--a situation that reflects both the tortuosity of the interendothelial clefts and the distribution of peritoneal capillaries within the interstitium. These comparisons reveal the peritoneal barrier as a relatively complex structure to model; and yet this model may be more representative of the general microcirculation, and thus shed light on systemic endothelial function in renal failure.

  3. Normalisation of glomerular filtration rate measurements

    International Nuclear Information System (INIS)

    White, A.J.; Strydom, W.J.

    1991-01-01

    The result of a glomerular filtration rate (GFR) measurement on a particular patient is of limited use to the referring physician since normal GFR values vary widely with the patient's age and build, etc. To overcome this problem, it is usual to normalise the measured GFR by dividing it by the patient's surface area and multiplying the result by the surface area of a 'standard' man. This transforms the measurment onto a scale which applies to all patients, young and old, large and small, where normal values fall within a well-defined range and where the degree of renal impairment can be quantified. We have examined the generally accepted surface area (SA) and the less well-known extracellular volume (ECV) normalisation methods of GFR measurements in a series of 110 patients. The results show that both methods produce essentially the same result; however, ECV normalisation is theoretically more correct, can be found directly without the patient's ECV being measured and does not require the use of empirical formulae. Mathematical justification for ECV normalisation is presented, and a proposed distribution pattern for the normalised measurement is introduced. A simple mathematical model shows that accurate GFR measurements can be made in the presence of an enlarged ECV, but normalisation of these will produce misleading low values. (orig.)

  4. Glomerular basement membrane lipidosis in Alagille syndrome.

    Science.gov (United States)

    Davis, Jessica; Griffiths, Ryan; Larkin, Kay; Rozansky, David; Troxell, Megan

    2010-06-01

    Alagille syndrome is characterized by a paucity of interlobular bile ducts with chronic cholestasis, cardiac, skeletal, and eye abnormalities and is associated predominantly with JAG1 mutations. Various renal abnormalities have been sporadically described. The classic renal histopathology described in Alagille syndrome is mesangiolipidosis, with lipid deposits predominately confined to the mesangium and minimal deposition within the glomerular basement membrane (GBM). We report a 5-year-old girl with Alagille syndrome who presented with persistent subnephrotic proteinuria and renal tubular acidosis. A renal biopsy showed GBM irregularities (mimicking membranous glomerulonephritis), mesangial sclerosis, and focal segmental glomerulosclerosis (FSGS) on light microscopy. Electron microscopy revealed few lipid inclusions within the mesangium but extensive inclusions along the GBM. These findings are mostly consistent with those reported previously in Alagille syndrome. However, the histologic distribution of lipid vacuoles is seemingly reversed in this patient and is uniquely accompanied by FSGS, emphasizing the spectrum of renal histopathology seen in Alagille syndrome. The proteinuria observed in this patient is likely attributed to significant GBM lipid deposition, which over time may contribute to the development of FSGS.

  5. Estimating Glomerular Filtration Rate in Older People

    Directory of Open Access Journals (Sweden)

    Sabrina Garasto

    2014-01-01

    Full Text Available We aimed at reviewing age-related changes in kidney structure and function, methods for estimating kidney function, and impact of reduced kidney function on geriatric outcomes, as well as the reliability and applicability of equations for estimating glomerular filtration rate (eGFR in older patients. CKD is associated with different comorbidities and adverse outcomes such as disability and premature death in older populations. Creatinine clearance and other methods for estimating kidney function are not easy to apply in older subjects. Thus, an accurate and reliable method for calculating eGFR would be highly desirable for early detection and management of CKD in this vulnerable population. Equations based on serum creatinine, age, race, and gender have been widely used. However, these equations have their own limitations, and no equation seems better than the other ones in older people. New equations specifically developed for use in older populations, especially those based on serum cystatin C, hold promises. However, further studies are needed to definitely accept them as the reference method to estimate kidney function in older patients in the clinical setting.

  6. Progress and controversies in unraveling the glomerular filtration mechanism.

    Science.gov (United States)

    Saritas, Turgay; Kuppe, Christoph; Moeller, Marcus J

    2015-05-01

    At first sight, the glomerular filter appears like a problem that should be easily solved. The majority of researchers view the filter like an impermeable wall perforated by specialized and size-selective pores (pore model). However, the fact that this model is in conflict with many of the experimental findings suggests that it may not yet be complete. In the more recent electrokinetic model, we have proposed including electrical effects (streaming potentials). The present review investigates how this can provide a relatively simple mechanistic explanation for the great majority of the so far unexplained characteristics of the filter, for example why the filter never clogs. Understanding how the glomerular filter functions is a prerequisite to investigate the pathogenesis of proteinuric glomerular diseases and the link between glomerular proteinuria and cardiovascular disease.

  7. Rapid induction of glomerular lipidosis in APA hamsters by streptozotocin.

    Science.gov (United States)

    Han, J. S.; Sugawara, Y.; Doi, K.

    1992-01-01

    The pathology of male Syrian hamsters of APA strain which were injected intraperitoneally with 40 mg/kg body weight of streptozotocin (SZ) at 2 months of age was examined. It showed long-lasting prominent hyperglycaemia and hyperlipidaemia with glucosuria and the development of glomerular lipidosis from 1 month after SZ-injection (1 MAI). Glomerular lesions were restricted to the juxtamedullary cortex at 1 MAI and then extended to the subcapsular cortex. At 3 MAI, glomerular lesions were characterized by focal segmental glomerulosclerosis showing segmental expansion of the mesangial area due to an increase of basement membrane-like material and mesangial cells with lipid droplets and foam cells. SZ-induced diabetic APA hamsters will be a useful model for the investigation of glomerular lipidosis and focal segmental glomerulosclerosis. Images Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 Fig. 8 Fig. 9 PMID:1533531

  8. Purge gas recovery of ammonia synthesis plant by integrated configuration of catalytic hydrogen-permselective membrane reactor and solid oxide fuel cell as a novel technology

    Science.gov (United States)

    Siavashi, Fakhteh; Saidi, Majid; Rahimpour, Mohammad Reza

    2014-12-01

    The purge gas emission of ammonia synthesis plant which contains hazardous components is one of the major sources of environmental pollution. Using integrated configuration of catalytic hydrogen-permselective membrane reactor and solid oxide fuel cell (SOFC) system is a new approach which has a great impact to reduce the pollutant emission. By application of this method, not only emission of ammonia and methane in the atmosphere is prevented, hydrogen is produced through the methane steam reforming and ammonia decomposition reactions that take place simultaneously in a catalytic membrane reactor. The pure generated hydrogen by recovery of the purge gas in the Pd-Ag membrane reactor is used as a feed of SOFC. Since water is the only byproduct of the electrochemical reaction in the SOFC, it is recycled to the reactor for providing the required water of the reforming reaction. Performance investigation of the reactor represents that the rate of hydrogen permeation increases with enhancing the reactor temperature and pressure. Also modeling results indicate that the SOFC performance improves with increasing the temperature and fuel utilization ratio. The generated power by recovery of the purging gas stream of ammonia synthesis plant in the Razi petrochemical complex is about 8 MW.

  9. Gas Permeability and Permselectivity of Poly(L-Lactic Acid)/SiOx Film and Its Application in Equilibrium-Modified Atmosphere Packaging for Chilled Meat.

    Science.gov (United States)

    Dong, Tungalag; Song, Shuxin; Liang, Min; Wang, Yu; Qi, Xiaojing; Zhang, Yuqin; Yun, Xueyan; Jin, Ye

    2017-01-01

    A layer of SiO x was deposited on the surface of poly(L-lactic acid) (PLLA) film to fabricate a PLLA/SiO x layered film, by plasma-enhanced chemical vapor deposition (PECVD) process. PLLA/SiO x film showed Young's modulus and tensile strength increased by 119.2% and 91.6%, respectively, over those of neat PLLA film. At 5 °C, the oxygen (O 2 ) and carbon dioxide (CO 2 ) permeability of PLLA/SiO x film decreased by 78.7% and 71.7%, respectively, and the CO 2 /O 2 permselectivity increased by 32.5%, compared to that of the neat PLLA film. When the PLLA/SiO x film was applied to the equilibrium-modified atmosphere packaging of chilled meat, the gas composition in packaging reached a dynamic equilibrium with 6% to 11% CO 2 and 8% to 13% O 2 . Combined with tea polyphenol pads, which effectively inhibited the microbial growth, the desirable color of meat was maintained and an extended shelf life of 52 d was achieved for the chilled meat. © 2016 Institute of Food Technologists®.

  10. Comparison of two different flow types on CO removal along a two-stage hydrogen permselective membrane reactor for methanol synthesis

    International Nuclear Information System (INIS)

    Rahimpour, M.R.; Mazinani, S.; Vaferi, B.; Baktash, M.S.

    2011-01-01

    Carbon monoxide (CO) is a gaseous pollutant with adverse effects on human health and the environment. Industrial chemical processes contribute significantly to CO accumulation in the atmosphere. One of the most important processes for controlling carbon monoxide emissions is the conversion of CO to methanol by catalytic hydrogenation. In this study, the effects of two different flow types on the rate of CO removal along a two-stage hydrogen permselective membrane reactor have been investigated. In the first configuration, fresh synthesis gas flows in the tube side of the membrane reactor co-currently with reacting material in the shell side, so that more hydrogen is provided in the first sections of the reactor. In the second configuration, fresh synthesis gas flows in the tube side of the membrane reactor counter-currently with reacting material in the shell side, so that more hydrogen is provided in the last sections of the reactor. For this membrane system, a one-dimensional dynamic plug flow model in the presence of catalyst deactivation was developed. Comparison between co-current and counter-current configurations shows that the reactor operates with higher conversion of CO and hydrogen permeation rate in the counter-current mode whereas; longer catalyst life is achieved in the co-current configuration. Enhancement of CO removal in the counter-current mode versus the co-current configuration results in an ultimate reduction in CO emissions into the atmosphere.

  11. Phlorizin Prevents Glomerular Hyperfiltration but not Hypertrophy in Diabetic Rats

    Directory of Open Access Journals (Sweden)

    Slava Malatiali

    2008-01-01

    Full Text Available The relationships of renal and glomerular hypertrophies to development of hyperfiltration and proteinuria early in streptozotocin-induced diabetes were explored. Control, diabetic, phlorizin-treated controls, and diabetic male Fischer rats were used. Phlorizin (an Na+-glucose cotransport inhibitor was given at a dose sufficient to normalize blood glucose. Inulin clearance (Cinulin and protein excretion rate (PER were measured. For morphometry, kidney sections were stained with periodic acid Schiff. At one week, diabetes PER increased 2.8-folds (P<.001, Cinulin increased 80% (P<.01. Kidney wet and dry weights increased 10%–12% (P<.05, and glomerular tuft area increased 9.3% (P<.001. Phlorizin prevented proteinuria, hyperfiltration, and kidney hypertrophy, but not glomerular hypertrophy. Thus, hyperfiltration, proteinuria, and whole kidney hypertrophy were related to hyperglycemia but not to glomerular growth. Diabetic glomerular hypertrophy constitutes an early event in the progression of glomerular pathology which occurs in the absence of mesangial expansion and persists even after changes in protein excretion and GFR are reversed through glycemic control.

  12. Hemodinâmica glomerular renal no roedor Calomys callosus

    Directory of Open Access Journals (Sweden)

    Mirian A. Boim

    1989-03-01

    Full Text Available A função renal do roedor Calomys callosus, envolvido no ciclo de transmissão de diversos agentes patogênicos para o homem foi avaliada no animal intacto, através da técnica de depuração e micropunção renal. Os resultados mostraram que este roedor apresenta níveis pressóricos, hematócrito e proteinas plasmáticas semelhantes aos dos ratos submetidos ao mesmo procedimento experimental. Os pesos corporal e renal, bem como a filtração glomerular global e por nefro assemelham-se aos do camundongo. Surpreendentemente estes roedores apresentaram significante número de glomérulos superficiais por rim, permitindo a avaliação da hemodinàmica glomerular. Apesar da pressão arterial semelhante à dos ratos Munich-Wistar (MW, a pressão hidráulica intraglomerular no Calomys callosus foi inferior. Esta redução foi conseqüente à menor resistência pós-glomerular quando comparada à dos ratos MW. O fluxo plasmático glomerular atingiu valor bastante elevado em relação à filtração glomerular por nefro, fato que não só compensaria a reduzida pressão intraglomerular, como também seria suficiente para elevar a filtração (por g/rim a níveis superiores neste roedor, pois o coeficiente de ultrafiltração glomerular (Kj foi semelhante ao do rato MW. O presente trabalho sugere que apesar das dificuldades técnicas que este animal impõe devido ao seu reduzido tamanho, o estudo da função renal global bem como da hemodinàmica glomerular é factível, podendo portanto ser utilizado como modelo para estudo da função renal em doenças tropicais.Renal function was characterized in Calomys callosus, a rodent which can participate in the transmission of several human diseases. The results showed that the pressures levels, hematocrit and plasmatic proteins were similar to rats submitted to the same experimental maneuvers. The corporal and renal weights, whole and single nephron glomerular filtration rates were similar to the mouse

  13. Renal extramedullary hematopoiesis: interstitial and glomerular pathology.

    Science.gov (United States)

    Alexander, Mariam P; Nasr, Samih H; Kurtin, Paul J; Casey, Edward T; Hernandez, Loren P Herrera; Fidler, Mary E; Sethi, Sanjeev; Cornell, Lynn D

    2015-12-01

    Renal extramedullary hematopoiesis is rarely recognized in the antemortem setting. We identified 14 patients with renal extramedullary hematopoiesis on antemortem specimens from 1994 to 2015. The mean age was 68 years (range 47-87 years); males predominated (M:F=9:5). All presented with renal insufficiency, including five (36%) with acute kidney injury. The mean serum creatinine at biopsy was 2.9 mg/dl (range 1.2-7.3 mg/dl). All had proteinuria (mean 7.9 g/24 h; range 0.5-28; n=13), including 9 with ≥3 g/24 h. Renal extramedullary hematopoiesis appeared histologically as an interstitial infiltrate (n=12) and/or a perirenal infiltrate (n=3) or mass-like lesion (n=1). Five were misdiagnosed as interstitial nephritis. Concurrent glomerular disease was prevalent and included fibrillary-like glomerulonephritis (n=3), chronic thrombotic microangiopathy (n=5), focal segmental glomerulosclerosis (n=6), and diabetic glomerulosclerosis (n=2). All patients had an underlying hematologic malignancy: primary myelofibrosis in 9, myeloproliferative neoplasm not otherwise specified in 1, essential thrombocythemia in 1, polycythemia vera in 1, and plasma cell myeloma in 2. Clinical follow-up was available in 12 patients, mean of 29 months (range 4-120 months). In 10 patients for whom treatment history could be obtained, 9 were treated with chemotherapy, and 1 was treated with steroids. The mean creatinine at last follow-up was 2 mg/dl (range 1.2-3.9 mg/dl) (n=9). Ten patients died in the follow-up period from their underlying hematological disease and had persistent renal disease. The two remaining patients had persistent chronic kidney disease. Renal extramedullary hematopoiesis should be considered in the differential diagnosis of interstitial infiltrates, particularly in the presence of a glomerulopathy and a hematologic malignancy.

  14. Nup98 FG domains from diverse species spontaneously phase-separate into particles with nuclear pore-like permselectivity.

    Science.gov (United States)

    Schmidt, Hermann Broder; Görlich, Dirk

    2015-01-06

    Nuclear pore complexes (NPCs) conduct massive transport mediated by shuttling nuclear transport receptors (NTRs), while keeping nuclear and cytoplasmic contents separated. The NPC barrier in Xenopus relies primarily on the intrinsically disordered FG domain of Nup98. We now observed that Nup98 FG domains of mammals, lancelets, insects, nematodes, fungi, plants, amoebas, ciliates, and excavates spontaneously and rapidly phase-separate from dilute (submicromolar) aqueous solutions into characteristic 'FG particles'. This required neither sophisticated experimental conditions nor auxiliary eukaryotic factors. Instead, it occurred already during FG domain expression in bacteria. All Nup98 FG phases rejected inert macromolecules and yet allowed far larger NTR cargo complexes to rapidly enter. They even recapitulated the observations that large cargo-domains counteract NPC passage of NTR⋅cargo complexes, while cargo shielding and increased NTR⋅cargo surface-ratios override this inhibition. Their exquisite NPC-typical sorting selectivity and strong intrinsic assembly propensity suggest that Nup98 FG phases can form in authentic NPCs and indeed account for the permeability properties of the pore.

  15. Investigation of cadmium-induced alterations in renal glomerular function

    International Nuclear Information System (INIS)

    Long, T.J.

    1982-01-01

    This research was designed to test the hypothesis that certain aspects of cadmium-induced renal dysfunction are the result of glomerular, rather than classic tubular, injury. To determine whether cadmium-induced proteinuria was due to altered glomerular function, cadmium was administered chronically at a concentration of 185 ppm in the drinking water. This protocol resulted in the production of proteinuria which when analyzed by high pressure liquid chromatography and radioimmunoassay was indistinguishable from that occurring in control rats. Glomerular filtration rate, renal blood flow, and filtration fraction were all significantly depressed after 20-30 weeks of exposure. In order to further investigate these alterations in glomerular function, an acute exposure model was developed. It was found that a single i.p. injection of cadmium in mercaptoethanol resulted in the onset of acute renal failure. The clinical picture was characterized by a reduction in glomerular filtrate rate of 50-90% within 24 hours, with partial to total recovery occurring by day 7 post-exposure. Histological evidence indicated that to a large extent the reduction in GFR was due to tubular blockade and/or backleak of filtrate across damaged tubules

  16. Rhophilin-1 Is a Key Regulator of the Podocyte Cytoskeleton and Is Essential for Glomerular Filtration

    Science.gov (United States)

    Lal, Mark A.; Andersson, Ann-Charlotte; Katayama, Kan; Xiao, Ziejie; Nukui, Masatoshi; Hultenby, Kjell; Wernerson, Annika

    2015-01-01

    Rhophilin-1 is a Rho GTPase-interacting protein, the biologic function of which is largely unknown. Here, we identify and describe the functional role of Rhophilin-1 as a novel podocyte-specific protein of the kidney glomerulus. Rhophilin-1 knockout mice were phenotypically normal at birth but developed albuminuria at about 2 weeks of age. Kidneys from severely albuminuric mice revealed widespread podocyte foot process effacement, thickening of the glomerular basement membrane, and FSGS-like lesions. The absence of any overt changes in the expression of podocyte proteins at the onset of proteinuria suggested that the primary cause of podocyte abnormalities in Rhpn1-null mice was the result of cell-autonomous, Rhophilin-1–dependent signaling events. In culture, Rhophilin-1 was detected at the plasma membrane leading edge of primary podocytes, where it elicited remodeling of the actin cytoskeleton network. This effect of Rhophilin-1 on actin cytoskeleton organization associated with inhibitory effects on Rho-dependent phosphorylation of the myosin regulatory light chain and stress fiber formation. Conversely, phosphorylation of myosin regulatory light chain increased in podocyte foot processes of Rhpn1−/− mice, implicating altered actinomyosin contractility in foot process effacement and compromised filtration capacity. Targeted deletion of RhoA in podocytes of Rhophilin-1 knockout mice exacerbated the renal injury. Taken together, our results indicate that Rhophilin-1 is essential for the integrity of the glomerular filtration barrier and that this protein is a key determinant of podocyte cytoskeleton architecture. PMID:25071083

  17. MC1R is dispensable for the proteinuria reducing and glomerular protective effect of melanocortin therapy

    Science.gov (United States)

    Qiao, Yingjin; Berg, Anna-Lena; Wang, Pei; Ge, Yan; Quan, Songxia; Zhou, Sijie; Wang, Hai; Liu, Zhangsuo; Gong, Rujun

    2016-01-01

    Melanocortin therapy by using adrenocorticotropic hormone (ACTH) or non-steroidogenic melanocortin peptides attenuates proteinuria and glomerular injury in experimental glomerular diseases and induces remission of nephrotic syndrome in patients with diverse glomerulopathies, even those resistant to steroids. The underlying mechanism remains elusive, but the role of melanocortin 1 receptor (MC1R) has been implicated and was examined here. Four patients with congenital red hair color and nephrotic syndrome caused by idiopathic membranous nephropathy or focal segmental glomerulosclerosis were confirmed by gene sequencing to bear dominant-negative MC1R mutations. Despite prior corticosteroid resistance, all patients responded to ACTH monotherapy and ultimately achieved clinical remission, inferring a steroidogenic-independent and MC1R-dispensable anti-proteinuric effect of melanocortin signaling. In confirmatory animal studies, the protective effect of [Nle4, D-Phe7]-α-melanocyte stimulating hormone (NDP-MSH), a potent non-steroidogenic pan-melanocortin receptor agonist, on the lipopolysaccharide elicited podocytopathy was completely preserved in MC1R-null mice, marked by reduced albuminuria and diminished histologic signs of podocyte injury. Moreover, in complementary in vitro studies, NDP-MSH attenuated the lipopolysaccharide elicited apoptosis, hypermotility and impairment of filtration barrier function equally in primary podocytes derived from MC1R-null and wild-type mice. Collectively, our findings suggest that melanocortin therapy confers a proteinuria reducing and podoprotective effect in proteinuric glomerulopathies via MC1R-independent mechanisms. PMID:27270328

  18. Optical, real-time monitoring of the glomerular filtration rate

    Science.gov (United States)

    Rabito, Carlos A.; Chen, Yang; Schomacker, Kevin T.; Modell, Mark D.

    2005-10-01

    An easy and accurate assessment of the renal function is a critical requirement for detecting the initial functional decline of the kidney induced by acute or chronic renal disease. A method for measuring the glomerular filtration rate is developed with the accuracy of clearance techniques and the convenience of plasma creatinine. The renal function is measured in rats as the rate of clearance determined from time-resolved transcutaneous fluorescence measurements of a new fluorescent glomerular filtration agent. The agent has a large dose-safety coefficient and the same space distribution and clearance characteristics as iothalamate. This new approach is a convenient and accurate way to perform real-time measurements of the glomerular filtration rate to detect early kidney disease before the renal function becomes severely and irreversibly compromised.

  19. Glomerular hyperfiltration and increased glomerular filtration surface are associated with renal function decline in normo- and microalbuminuric type 2 diabetes.

    Science.gov (United States)

    Moriya, Tatsumi; Tsuchiya, Akiko; Okizaki, Shin-ichiro; Hayashi, Akinori; Tanaka, Keiji; Shichiri, Masayoshi

    2012-03-01

    The prevalence of glomerular hyperfiltration in type 2 diabetic patients varies widely. Here we studied whether glomerular hyperfiltration in diabetic nephropathy in type 2 patients is related to renal structural changes and predicts the functional development of diabetic nephropathy. Thirty normo- or microalbuminuric type 2 diabetic patients having a renal biopsy were followed every 6 months for a mean of 6.2 years. The glomerular filtration rate (GFR) at the time of biopsy, determined by iohexol clearance, correlated with filtration surface per glomerulus, but no other quantitative microscopic morphometric parameter. The filtration surface was positively associated with the decrease in GFR during the first year but not associated in subsequent years following the renal biopsy. The GFR showed a statistically significant linear decrease in 9 of the 30 patients; however, slopes of the regression lines were almost zero in 11 patients. The GFR increased and decreased in a parabolic manner in two patients. Seven of the nine patients with a statistically significant decline in renal function did not show any appreciable worsening of albuminuria, while two patients developed persistent proteinuria. Thus, in renal biopsy-proven normo- or microalbuminuric type 2 diabetic patients, glomerular hyperfiltration is closely associated with an increased glomerular filtration surface. An elevated GFR predicts its subsequent decline, which may occur without worsening of albuminuria.

  20. DETECTION OF OCCULT GLOMERULAR DYSFUNCTION IN GLUCOSE SIX PHOSPHATE DEHYDROGENASE DEFICIENCY ANEMIA

    Directory of Open Access Journals (Sweden)

    Gehan Abdel Hakeem

    2016-08-01

    G6PD deficiency anemia is associated with a variable degree of glomerular dysfunction during acute hemolytic episodes. This glomerular dysfunction can result in chronic subclinical or occult chronic kidney injury.

  1. Glomerular filtration rate determined in conjunction with routine renal scanning

    International Nuclear Information System (INIS)

    Jackson, J.H.; Blue, P.W.; Ghaed, N.

    1985-01-01

    A method has been developed to estimate glomerular filtration rate using computer evaluation of images obtained during routine renal scanning. The technique requires less than 40 minutes of imaging time, requires only a single blood sample and correlates highly with 24 hour creatinine clearance

  2. Indexing Glomerular Filtration Rate to Body Surface Area

    DEFF Research Database (Denmark)

    Redal-Baigorri, Belén; Rasmussen, Knud; Heaf, James Goya

    2014-01-01

    BACKGROUND: Kidney function is mostly expressed in terms of glomerular filtration rate (GFR). A common feature is the expression as ml/min per 1.73 m(2) , which represents the adjustment of the individual kidney function to a standard body surface area (BSA) to allow comparison between individuals...

  3. Estimated Glomerular Filtration Rate and Risk of Survival in Acute ...

    African Journals Online (AJOL)

    Objective: To assess the risk of survival in acute stroke using the MDRD equation derived estimated glomerular filtration rate. Design: A prospective observational cross-sectional study. Setting: Medical wards of a tertiary care hospital. Subjects: Eighty three acute stroke patients had GFR calculated within 48 hours of ...

  4. Estimated glomerular filtration rate at initiation of hemodialysis in a ...

    African Journals Online (AJOL)

    Background: Renal replacement therapy is indicated for patients with end-stage renal disease (ESRD). The glomerular filtration rate (GFR) of ESRD patients at initiation of hemodialysis vary depending on several factors including comorbidities, physicians' practice and geographical region amongst others. Aim: We ...

  5. Glomerular filtration rate in steady state children with sickle cell ...

    African Journals Online (AJOL)

    Background: Sickle cell anaemia (SCA) affects mostly people of African origin. It causes kidney problems termed Sickle cell nephropathy (SCN). Increased glomerular filtration rate (GFR) has been documented as one of the functional abnormalities seen in young SCA patients. Objective: To estimate GFR in Nigerian ...

  6. Effect of glycaemic control on glomerular filtration rate in Diabetes ...

    African Journals Online (AJOL)

    Background: Glomerular filtration rate (GFR) is a widely accepted parameter in assessing overall renal function. This study sought to assess the effect of glucose lowering on GFR in diabetic patients admitted for short term therapy at Mulago hospital. Methods: This was a descriptive study where consenting patients were ...

  7. Evaluation of Serum Cystatin C as an Indicator of Glomerular ...

    African Journals Online (AJOL)

    Background: The Glomerular Filtration Rate (GFR) is the best indicator of renal function. Serum cystatin C has been introduced as an endogenous marker of GFR. However, there are conflicting reports regarding its use in pregnancy and pre-eclampsia. We aimed to assess the GFR changes in pre-eclampsia, evaluate the ...

  8. Structural Alterations of the Glomerular Wall And Vessels in Early ...

    African Journals Online (AJOL)

    Structural Alterations of the Glomerular Wall And Vessels in Early Stages of Diabetes Mellitus: Light and Transmission Electron Microscopic Study. ... The second group of 20 (the experimental group) was injected intraperitoneally by a single dose of streptozotocin to induce hyperglycemia. Rats were sacrificed after ten days, ...

  9. Important clinical and laboratory correlates of glomerular filtration ...

    African Journals Online (AJOL)

    2015-02-03

    Feb 3, 2015 ... associated with laboratory indicators of hemolysis in this group of patients.[6] Progression of sickle nephropathy can. Important clinical and laboratory correlates of glomerular filtration rate in sickle cell anemia. AJ Madu, A Ubesie1, S Ocheni, J Chinawa1, KA Madu2, OG Ibegbulam, C Nlemadim3, A Eze3.

  10. Hemodinâmica glomerular renal no roedor Calomys callosus

    Directory of Open Access Journals (Sweden)

    Mirian A. Boim

    1989-03-01

    Full Text Available A função renal do roedor Calomys callosus, envolvido no ciclo de transmissão de diversos agentes patogênicos para o homem foi avaliada no animal intacto, através da técnica de depuração e micropunção renal. Os resultados mostraram que este roedor apresenta níveis pressóricos, hematócrito e proteinas plasmáticas semelhantes aos dos ratos submetidos ao mesmo procedimento experimental. Os pesos corporal e renal, bem como a filtração glomerular global e por nefro assemelham-se aos do camundongo. Surpreendentemente estes roedores apresentaram significante número de glomérulos superficiais por rim, permitindo a avaliação da hemodinàmica glomerular. Apesar da pressão arterial semelhante à dos ratos Munich-Wistar (MW, a pressão hidráulica intraglomerular no Calomys callosus foi inferior. Esta redução foi conseqüente à menor resistência pós-glomerular quando comparada à dos ratos MW. O fluxo plasmático glomerular atingiu valor bastante elevado em relação à filtração glomerular por nefro, fato que não só compensaria a reduzida pressão intraglomerular, como também seria suficiente para elevar a filtração (por g/rim a níveis superiores neste roedor, pois o coeficiente de ultrafiltração glomerular (Kj foi semelhante ao do rato MW. O presente trabalho sugere que apesar das dificuldades técnicas que este animal impõe devido ao seu reduzido tamanho, o estudo da função renal global bem como da hemodinàmica glomerular é factível, podendo portanto ser utilizado como modelo para estudo da função renal em doenças tropicais.

  11. Contribution of glomerular morphometry to the diagnosis of pediatric nephropathies

    Directory of Open Access Journals (Sweden)

    Mariana Barreto Marini

    2016-01-01

    Full Text Available Only a few studies describe histopathological changes in renal biopsies performed in pediatric patients. This study was conducted to identify an association between morphometric data in renal biopsies and renal function of these patients. Fifty-nine individuals with ages between 2 and 18 years old were selected, who were divided into six groups consisting of frequent nephropathies in children and adolescents and one control group. Proteinuria, urea, and creatinine values of the patients were recorded. Interactive image analysis software Leica QWin[®]was used for morpho- metric analysis of Bowman′s capsule, glomerular capillary tuft, and Bowman′s space area. The mean glomerular tuft area was higher in the membranous glomerulopathy group than in the podo- cytopathy group (57,101 ± 25,094 vs. 27,420 c ± 6279 µm2; P <0.05. The median of Bowman′s space area was higher in the control group than in the podocytopathy group and in the thin basement membrane/Alport syndrome group [12,210 (7676-26,945 vs. 5801 (3031-7852 µm2; P <0.01 and 12210 (7676-26,945 vs. 4183 (3797-7992 µm2; P <0.01, respectively]. There was a positive and significant correlation between Bowman′s capsule area and the levels of proteinuria, creatinine, and urea of the patients, as well as between the glomerular tuft area and the levels of proteinuria, creatinine, and urea in the patients, regardless of their nephropathy. Glomerular morphometry may contribute to the diagnosis of some glomerulopathies and the association between glomerular morphometric parameters, and laboratory data may promote a better understanding of the prognosis of these patients.

  12. Persistent decline in estimated but not measured glomerular filtration rate on tenofovir may reflect tubular rather than glomerular toxicity

    NARCIS (Netherlands)

    Vrouenraets, Saskia M. E.; Fux, Christoph A.; Wit, Ferdinand W. N. M.; Garcia, Evian Fernandez; Furrer, Hansjakob; Brinkman, Kees; Hoek, Frans J.; Abeling, Nico G. G. M.; Krediet, Ray T.; Reiss, Peter

    2011-01-01

    Tenofovir disoproxil fumarate (TDF) has been associated with proximal renal tubulopathy and reduction in estimated glomerular filtration rate (eGFR), without accounting for the tubular secretion of creatinine. A substudy was performed among 19 participants of a randomized 48-week trial, comparing

  13. The glomerular filtration rate during pregnancy : Saline infusion enhances the glomerular filtration rate in the pregnant rat

    NARCIS (Netherlands)

    Faas, MM; Schuiling, GA; Klok, PA; Valkhof, N; Bakker, WW

    1996-01-01

    The glomerular filtration rate (GFR) of pregnant rats is generally believed to exceed non-pregnant values. This notion is primarily based upon standard inulin clearances. However, the inulin clearance requires continuous infusion of inulin usually dissolved in saline. Since saline infusion per se in

  14. Crk1/2-dependent signaling is necessary for podocyte foot process spreading in mouse models of glomerular disease

    Science.gov (United States)

    George, Britta; Verma, Rakesh; Soofi, Abdulsalam A.; Garg, Puneet; Zhang, Jidong; Park, Tae-Ju; Giardino, Laura; Ryzhova, Larisa; Johnstone, Duncan B.; Wong, Hetty; Nihalani, Deepak; Salant, David J.; Hanks, Steven K.; Curran, Tom; Rastaldi, Maria Pia; Holzman, Lawrence B.

    2012-01-01

    The morphology of healthy podocyte foot processes is necessary for maintaining the characteristics of the kidney filtration barrier. In most forms of glomerular disease, abnormal filter barrier function results when podocytes undergo foot process spreading and retraction by remodeling their cytoskeletal architecture and intercellular junctions during a process known as effacement. The cell adhesion protein nephrin is necessary for establishing the morphology of the kidney podocyte in development by transducing from the specialized podocyte intercellular junction phosphorylation-mediated signals that regulate cytoskeletal dynamics. The present studies extend our understanding of nephrin function by showing that nephrin activation in cultured podocytes induced actin dynamics necessary for lamellipodial protrusion. This process required a PI3K-, Cas-, and Crk1/2-dependent signaling mechanism distinct from the previously described nephrin-Nck1/2 pathway necessary for assembly and polymerization of actin filaments. Our present findings also support the hypothesis that mechanisms governing lamellipodial protrusion in culture are similar to those used in vivo during foot process effacement in a subset of glomerular diseases. In mice, podocyte-specific deletion of Crk1/2 prevented foot process effacement in one model of podocyte injury and attenuated foot process effacement and associated proteinuria in a delayed fashion in a second model. In humans, focal adhesion kinase and Cas phosphorylation — markers of focal adhesion complex–mediated Crk-dependent signaling — was induced in minimal change disease and membranous nephropathy, but not focal segmental glomerulosclerosis. Together, these observations suggest that activation of a Cas-Crk1/2–dependent complex is necessary for foot process effacement observed in distinct subsets of human glomerular diseases. PMID:22251701

  15. Building barriers.

    Science.gov (United States)

    Turksen, Kursad

    2017-10-02

    Formation of tissue barriers starts in early development where it is critical for normal cell fate selection, differentiation and organogenesis. Barrier maintenance is critical to the ongoing function of organs during adulthood and aging. Dysfunctional tissue barrier formation and function at any stage of the organismal life cycle underlies many disease states.

  16. Captoril suppresses glomerular filtration rate but not blood flow in the affected kidney in renovascular hypertension

    International Nuclear Information System (INIS)

    Fommei, E.; Ghione, S.; Palla, L.; Giaconi, S.; Morraccini, P.; Palombo, C.; Rosa, C.; Gazzetti, P.; Donato, L.

    1985-01-01

    The acute effects of Captopril on glomerular filtration rate and blood flow of the kidney affected by unilateral renal artery stenosis in a patient with renovascular hypertension are reported. The contribution of the stenotic kidney to total glomerular filtration rate and blood flow was assessed by scintigraphic methods, using respectively the glomerular tracer 99m Tc-DTPA and 99m Tc-Albumin microspheres. Captopril induced a marked reduction of glomerular filtration without affecting blood flow. This finding indicates a profound dysruption of Angiotensin II - dependent autoregulation of the glomerular filtration induced by converting enzyme inhibition in renal artery stenosis

  17. Paracellular barrier and channel functions of TJ claudins in organizing biological systems: advances in the field of barriology revealed in knockout mice.

    Science.gov (United States)

    Tamura, Atsushi; Tsukita, Sachiko

    2014-12-01

    Claudin was first identified as a four-transmembrane protein in the tight junctions (TJs) between epithelial cells. The claudin family has 27 members, which are specifically expressed depending on the epithelial cell type. Accumulating evidence has revealed that claudins are responsible for the paracellular barrier that prevents molecules from passing through epithelial cell sheets. In addition, the extracellular domains of some claudins enable them to act as a permselective paracellular channel for specific molecules, including ions and/or non-ionic solutes. Recent studies using claudin knockout mice revealed that the loss of claudins' specific paracellular barrier and/or channel functions affects specific biological functions and leads to pathological states. In this review, considering recent findings in vivo, we describe how, sometimes in concert with canonical transporters and channels, the paracellular barrier and channel functions of claudins sophisticatedly organize biological systems. Copyright © 2014. Published by Elsevier Ltd.

  18. Cell biology of mesangial cells: the third cell that maintains the glomerular capillary.

    Science.gov (United States)

    Kurihara, Hidetake; Sakai, Tatsuo

    2017-03-01

    The renal glomerulus consists of glomerular endothelial cells, podocytes, and mesangial cells, which cooperate with each other for glomerular filtration. We have produced monoclonal antibodies against glomerular cells in order to identify different types of glomerular cells. Among these antibodies, the E30 clone specifically recognizes the Thy1.1 molecule expressed on mesangial cells. An injection of this antibody into rats resulted in mesangial cell-specific injury within 15 min, and induced mesangial proliferative glomerulonephritis in a reproducible manner. We examined the role of mesangial cells in glomerular function using several experimental tools, including an E30-induced nephritis model, mesangial cell culture, and the deletion of specific genes. Herein, we describe the characterization of E30-induced nephritis, formation of the glomerular capillary network, mesangial matrix turnover, and intercellular signaling between glomerular cells. New molecules that are involved in a wide variety of mesangial cell functions are also introduced.

  19. Glomerular Glucocorticoid Receptors Expression and Clinicopathological Types of Childhood Nephrotic Syndrome.

    Science.gov (United States)

    Gamal, Yasser; Badawy, Ahlam; Swelam, Salwa; Tawfeek, Mostafa S K; Gad, Eman Fathalla

    2017-02-01

    Glucocorticoids are primary therapy of idiopathic nephrotic syndrome (INS). However, not all children respond to steroid therapy. We assessed glomerular glucocorticoid receptor expression in fifty-one children with INS and its relation to response to steroid therapy and to histopathological type. Clinical, laboratory and glomerular expression of glucocorticoid receptors were compared between groups with different steroid response. Glomerular glucocorticoid expression was slightly higher in controls than in minimal change early responders, which in turn was significantly higher than in minimal change late responders. There was significantly lower glomerular glucocorticoid receptor expression in steroid-resistance compared to early responders, late responders and controls. Glomerular glucocorticoid expression was significantly higher in all minimal change disease (MCD) compared to focal segmental glomerulosclerosis. In INS, response to glucocorticoid is dependent on glomerular expression of receptors and peripheral expression. Evaluation of glomerular glucocorticoid receptor expression at time of diagnosis of NS can predict response to steroid therapy.

  20. Clinician’s use of automated reports of estimated glomerular filtration rate: A qualitative study

    Directory of Open Access Journals (Sweden)

    Smith David H

    2012-11-01

    Full Text Available Background There is a growing awareness in primary care of the importance of identifying patients with chronic kidney disease (CKD so that they can receive appropriate clinical care; one method that has been widely embraced is the use of automated reporting of estimated glomerular filtration rate (eGFR by clinical laboratories. We undertook a qualitative study to examine how clinicians use eGFR in clinical decision making, patient communication issues, barriers to use of eGFR, and suggestions to improve the clinical usefulness of eGFR reports. Methods Our study used qualitative methods with structured interviews among primary care clinicians including both physicians and allied health providers, recruited from Kaiser Permanente Northwest, a non-profit health maintenance organization. Results We found that clinicians generally held favorable views toward eGFR reporting but did not use eGFR to replace serum creatinine in their clinical decision-making. Clinicians used eGFR as a tool to help identify CKD, educate patients about their kidney function and make treatment decisions. Barriers noted by several clinicians included a desire for greater education regarding care for patients with CKD and tools to facilitate discussion of eGFR findings with patients. Conclusions The manner in which clinicians use eGFRs appears to be more complex than previously understood, and our study illustrates some of the efforts that might be usefully undertaken (e.g. specific clinician education when encouraging further promulgation of eGFR reporting and usage.

  1. A simple method for the estimation of glomerular filtration rate

    International Nuclear Information System (INIS)

    Groth, T.; Tengstroem, B.

    1977-01-01

    A simple method is presented for indirect estimation of the glomerular filtration rate from two venous blood samples, drawn after a single injection of a small dose of [ 125 I]sodium iothalamate (10 μCi). The method does not require exact dosage, as the first sample, taken after a few minutes (t=5 min) after injection, is used to normilize the value of the second sample, which should be taken in between 2-4 h after injection. The glomerular filtration rate, as measured by standard inulin clearance, may then be predicted from the logarithm of the normalized value and linear regression formulas with a standard error of estimate of the order of 1-2 ml/min/1.73 m 2 . The slope-intercept method for direct estimation of glomerular filtration rate is also evaluated and found to significantly underestimate standard insulin clearance. The normalized 'single-point' method is concluded to be superior to the slope-intercept method and more sophisticated methods using curve fitting technique, with regard to predictive force and clinical applicability. (Auth.)

  2. Intraglomerular microcirculation: measurements of single glomerular loop flow in rats.

    Science.gov (United States)

    Steinhausen, M; Zimmerhackl, B; Thederan, H; Dussel, R; Parekh, N; Esslinger, H U; von Hagens, G; Komitowski, D; Dallenbach, F D

    1981-08-01

    With the use of a new fluorescent microscopic technique, we were able to measure the mean intracapillary velocities and pressures of single capillary loops of renal glomeruli of living rats. The technique involved photographing and recording the flow of fluorescent latex particles through the glomerular loops with a television monitor. In 25 rats the single glomerular loop flow velocity was 781 +/- (SD) 271 micrometers . sec-1. The mean diameter of the capillary loops measured 8.4 +/- 1.4 micrometers; their lengths were 72.3 +/- 37.5 micrometers. From the decrease in velocity of flow along the capillary loop, we were able to evaluate the filtration equivalent for the capillary surface. It was possible to measure intracapillary pressures of single glomerular loops continuously under microscopic control. High intracapillary pressures correlated with high intracapillary velocities. From the data we obtained, we were unable to calculate a filtration equilibrium at the ends of the observed capillary loops. For further correlations, we injected the glomeruli we had studied in the living state and examined them with the scanning electron microscope.

  3. Loss of endogenous thymosin β4 accelerates glomerular disease.

    Science.gov (United States)

    Vasilopoulou, Elisavet; Kolatsi-Joannou, Maria; Lindenmeyer, Maja T; White, Kathryn E; Robson, Michael G; Cohen, Clemens D; Sebire, Neil J; Riley, Paul R; Winyard, Paul J; Long, David A

    2016-11-01

    Glomerular disease is characterized by morphologic changes in podocyte cells accompanied by inflammation and fibrosis. Thymosin β 4 regulates cell morphology, inflammation, and fibrosis in several organs and administration of exogenous thymosin β 4 improves animal models of unilateral ureteral obstruction and diabetic nephropathy. However, the role of endogenous thymosin β 4 in the kidney is unknown. We demonstrate that thymosin β 4 is expressed prominently in podocytes of developing and adult mouse glomeruli. Global loss of thymosin β 4 did not affect healthy glomeruli, but accelerated the severity of immune-mediated nephrotoxic nephritis with worse renal function, periglomerular inflammation, and fibrosis. Lack of thymosin β 4 in nephrotoxic nephritis led to the redistribution of podocytes from the glomerular tuft toward the Bowman capsule suggesting a role for thymosin β 4 in the migration of these cells. Thymosin β 4 knockdown in cultured podocytes also increased migration in a wound-healing assay, accompanied by F-actin rearrangement and increased RhoA activity. We propose that endogenous thymosin β 4 is a modifier of glomerular injury, likely having a protective role acting as a brake to slow disease progression. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

  4. Rheological Influence Upon the Glomerular Podocyte and Resultant Mechanotransduction

    Directory of Open Access Journals (Sweden)

    Simona Pichler Sekulic

    2015-03-01

    Full Text Available The glomerular podocyte is exposed to numerous mechanical forces as a constituent of the glomerular filtration apparatus. This includes fluid shear stress (FSS displaced upon the podocytic foot process's apical, lateral, and basal surfaces. Even in the face of continuous flow the podocyte is capable of contributing to physiologic filtration, however with pathologic levels of hyperfiltration there is increased FSS placed upon the cell. The mechanisms by which the podocyte detects and responds to FSS are topics of recent investigations, with the aim to clarify the way these cells are injured and/or adapt in times of hyperfiltration and disease states. As the pathogenesis of numerous glomerulopathies is contingent on the status of the podocyte, understanding the manner that these cells can be modified by FSS is essential. Likewise, determination of the effect of such mechanical forces upon other resident cells of the renal corpuscle would reveal the contribution of FSS in the progression of glomerular diseases. The biochemical manner in which podocytes sense and respond to FSS, that is mechanotransduction, will be discussed.

  5. Genetic analysis of intracapillary glomerular lipoprotein deposits in aging mice.

    Directory of Open Access Journals (Sweden)

    Gerda A Noordmans

    Full Text Available Renal aging is characterized by functional and structural changes like decreased glomerular filtration rate, and glomerular, tubular and interstitial damage. To gain insight in pathways involved in renal aging, we studied aged mouse strains and used genetic analysis to identify genes associated with aging phenotypes.Upon morphological screening in kidneys from 20-month-old mice from 26 inbred strains we noted intracapillary PAS-positive deposits. The severity of these deposits was quantified by scoring of a total of 50 glomeruli per section (grade 0-4. Electron microscopy and immunohistochemical staining for apoE, apoB, apoA-IV and perilipin-2 was performed to further characterize the lesions. To identify loci associated with these PAS-positive intracapillary glomerular deposits, we performed haplotype association mapping.Six out of 26 mouse strains showed glomerular PAS-positive deposits. The severity of these deposits varied: NOD(0.97, NZW(0.41, NON(0.30, B10(0.21, C3 H(0.9 and C57BR(0.7. The intracapillary deposits were strongly positive for apoE and weakly positive for apoB and apoA-IV. Haplotype association mapping showed a strong association with a 30-Kb haplotype block on Chr 1 within the Esrrg gene. We investigated 1 Mb on each site of this region, which includes the genes Spata17, Gpatch2, Esrrg, Ush2a and Kctd3.By analyzing 26 aged mouse strains we found that some strains developed an intracapillary PAS and apoE-positive lesion and identified a small haplotype block on Chr 1 within the Esrrg gene to be associated with these lipoprotein deposits. The region spanning this haplotype block contains the genes Spata17, Gpatch2, Esrrg, Ush2a and Kctd3, which are all highly expressed in the kidney. Esrrg might be involved in the evolvement of these glomerular deposits by influencing lipid metabolism and possibly immune reponses.

  6. Aldosterone-mineralocorticoid receptor promotes urine prostasin through glomerular barrier injury and not tissue abundance

    DEFF Research Database (Denmark)

    Stolzenburg Oxlund, Christina; Kurt, B.; Schwarzensteiner, I.

    2015-01-01

    Objective: Low salt intake or infusion with the mineralocorticoid hormone aldosterone increases the abundance of proteolytically activated gamma ENaC in rat kidney. Prostasin is a serine proteinase GPI-anchored to the apical membrane of renal principal cells. It was hypothesized that the aldoster......Objective: Low salt intake or infusion with the mineralocorticoid hormone aldosterone increases the abundance of proteolytically activated gamma ENaC in rat kidney. Prostasin is a serine proteinase GPI-anchored to the apical membrane of renal principal cells. It was hypothesized...... that the aldosterone- mineralocorticoid receptor (MR) pathway maintains prostasin abundance in human kidney. Design and method: Urine and plasma prostasin was measured by ELISA in urine and plasma from a cohort of type-2 diabetes patients (n = 112) with treatment resistant hypertension before and after intervention...

  7. Change in glomerular volume and its clinicopathological impact after kidney transplantation.

    Science.gov (United States)

    Kobayashi, Akimitsu; Yamamoto, Izumi; Katsumata, Haruki; Yamakawa, Takafumi; Mafune, Aki; Nakada, Yasuyuki; Koike, Kentaro; Mitome, Jun; Miki, Jun; Yamada, Hiroki; Tanno, Yudo; Ohkido, Ichiro; Tsuboi, Nobuo; Yokoyama, Keitaro; Yamamoto, Hiroyasu; Yokoo, Takashi

    2015-07-01

    Both immunological and non-immunological etiologies affect graft function after kidney transplantation, including acute rejection, calcineurin inhibitor toxicity, and a recurrence of glomerulonephritis. Glomerular enlargement or glomerular sclerosis due to glomerular hyperfiltration related to increased renal blood flow is another cause. Although the glomerular volume in baseline biopsies predicts late allograft function, the relationship between allograft function and the annual changes in glomerular volume after kidney transplantation are unclear. We investigated changes in glomerular volume after kidney transplantation and their clinicopathological relationship. We enrolled 23 patients with stable kidney function without an episode of rejection or any complication resulting in a functional decrease in the graft. We measured glomerular volume (GV) using the Weibel-Gomez method and glomerular density (GD) using 0,1 h biopsy samples as baseline controls and 1 yr biopsy samples and investigated the association between the changes in them and clinical parameters, including graft function, proteinuria, and renal hemodynamic markers, including effective renal plasma flow (ERPF) and filtration fraction (FF). The ERPF was calculated from a 99mTc-mercaptoacetyltriglycine (MAG3) renogram. The GV and ERPF increased significantly 1 yr after kidney transplantation. In contrast, proteinuria decreased significantly and Δproteinuria (1 yr - 1 month after transplantation) was correlated with ΔGV (P Glomerular enlargement 1 yr after transplantation may be related to improved proteinuria. It is possible that glomerular enlargement serves as a renal adaptation after kidney transplantation. © 2015 Asian Pacific Society of Nephrology.

  8. A High-Powered View of the Filtration Barrier

    Science.gov (United States)

    Peti-Peterdi, János; Sipos, Arnold

    2015-01-01

    Multiphoton excitation fluorescence microscopy is a powerful noninvasive imaging technique for the deep optical sectioning of living tissues. Its application in several intact tissues is a significant advance in our understanding of organ function, including renal pathophysiological mechanisms. The glomerulus, the filtering unit in the kidney, is one good example of a relatively inaccessible and complex structure, with cell types that are otherwise difficult to study at high resolution in their native environment. In this article, we address the application, advantages, and limitations of this imaging technology for the study of the glomerular filtration barrier and the controversy it recently generated regarding the glomerular filtration of macromolecules. More advanced and accurate multiphoton determinations of the glomerular sieving coefficient that are presented here dismiss previous claims on the filtration of nephrotic levels of albumin. The sieving coefficient of 70-kD dextran was found to be around 0.001. Using a model of focal segmental glomerulosclerosis, increased filtration barrier permeability is restricted only to areas of podocyte damage, consistent with the generally accepted role of podocytes and the glomerular origin of albuminuria. Time-lapse imaging provides new details and important in vivo confirmation of the dynamics of podocyte movement, shedding, replacement, and the role of the parietal epithelial cells and Bowman's capsule in the pathology of glomerulosclerosis. PMID:20576805

  9. Glomerular hyperfiltration in children with cancer: prevalence and a hypothesis

    Energy Technology Data Exchange (ETDEWEB)

    Kwatra, Neha S. [Children' s National Medical Center, Division of Diagnostic Imaging and Radiology, Washington, DC (United States); Boston Children' s Hospital, Department of Radiology, Boston, MA (United States); Meany, Holly J. [Children' s National Medical Center, Department of Hematology/Oncology, Washington, DC (United States); Ghelani, Sunil J. [Boston Children' s Hospital, Department of Cardiology, Boston, MA (United States); Zahavi, David [The Johns Hopkins University School of Medicine, Department of Pathology, Baltimore, MD (United States); Pandya, Nayan; Majd, Massoud [Children' s National Medical Center, Division of Diagnostic Imaging and Radiology, Washington, DC (United States)

    2017-02-15

    Glomerular hyperfiltration has recently been reported in children with malignancies and has been attributed to increased solute from breakdown of tumor tissues. To evaluate the prevalence of hyperfiltration in the pediatric oncology population and explore its pathophysiological mechanism. Tc-99 m diethylenetriaminepentaacetic acid (DTPA) glomerular filtration rate (GFR) examinations (437 studies) and medical records of 177 patients <21 years of age diagnosed with a malignancy between January 2005 and October 2013 were retrospectively reviewed. Hyperfiltration was defined as a GFR ≥ 160 ml/min/1.73 m{sup 2}. Seventy-seven (43.5%) patients had hyperfiltration in at least one GFR exam. A significantly higher percentage of patients with central nervous system (CNS) tumors (63.6%) had hyperfiltration when compared to other tumor types (27.3%, P < 0.001). No association was found between hyperfiltration and age, gender, race or bone marrow involvement. There was a significant trend toward decreasing hyperfiltration after the second cycle of chemotherapy (P = 0.006) and a significant increase in subjects with low GFR (<100 ml/min/1.73 m{sup 2}) with increasing number of cycles of chemotherapy (P = 0.005). Glomerular hyperfiltration is common in children with malignancies at diagnosis and during initial cycles of chemotherapy. It is particularly prevalent in patients with central nervous tumors, which are frequently smaller in volume. Therefore, the pathophysiological mechanism of hyperfiltration cannot be explained solely on the basis of large tumor volume and subsequent cell breakdown. We hypothesize that host hypermetabolic state plays an important role in pathophysiology of hyperfiltration. (orig.)

  10. Mechanisms responsible for decreased glomerular filtration in hibernation and hypothermia

    Science.gov (United States)

    Tempel, G. E.; Musacchia, X. J.; Jones, S. B.

    1977-01-01

    Measurements of blood pressure, heart rate, red blood cell and plasma volumes, and relative distribution of cardiac output were made on hibernating and hypothermic adult male and female golden hamsters weighing 120-140 g to study the mechanisms underlying the elimination or marked depression of renal function in hibernation and hypothermia. The results suggest that the elimination or marked depression in renal function reported in hibernation and hypothermia may partly be explained by alterations in cardiovascular system function. Renal perfusion pressure which decreases nearly 60% in both hibernation and hypothermia and a decrease in plasma volume of roughly 35% in the hypothermic animal might both be expected to markedly alter glomerular function.

  11. A neural network model for olfactory glomerular activity prediction

    Science.gov (United States)

    Soh, Zu; Tsuji, Toshio; Takiguchi, Noboru; Ohtake, Hisao

    2012-12-01

    Recently, the importance of odors and methods for their evaluation have seen increased emphasis, especially in the fragrance and food industries. Although odors can be characterized by their odorant components, their chemical information cannot be directly related to the flavors we perceive. Biological research has revealed that neuronal activity related to glomeruli (which form part of the olfactory system) is closely connected to odor qualities. Here we report on a neural network model of the olfactory system that can predict glomerular activity from odorant molecule structures. We also report on the learning and prediction ability of the proposed model.

  12. Proximal tubular hypertrophy and enlarged glomerular and proximal tubular urinary space in obese subjects with proteinuria.

    Directory of Open Access Journals (Sweden)

    Ana Tobar

    Full Text Available BACKGROUND: Obesity is associated with glomerular hyperfiltration, increased proximal tubular sodium reabsorption, glomerular enlargement and renal hypertrophy. A single experimental study reported an increased glomerular urinary space in obese dogs. Whether proximal tubular volume is increased in obese subjects and whether their glomerular and tubular urinary spaces are enlarged is unknown. OBJECTIVE: To determine whether proximal tubules and glomerular and tubular urinary space are enlarged in obese subjects with proteinuria and glomerular hyperfiltration. METHODS: Kidney biopsies from 11 non-diabetic obese with proteinuria and 14 non-diabetic lean patients with a creatinine clearance above 50 ml/min and with mild or no interstitial fibrosis were retrospectively analyzed using morphometric methods. The cross-sectional area of the proximal tubular epithelium and lumen, the volume of the glomerular tuft and of Bowman's space and the nuclei number per tubular profile were estimated. RESULTS: Creatinine clearance was higher in the obese than in the lean group (P=0.03. Proteinuria was similarly increased in both groups. Compared to the lean group, the obese group displayed a 104% higher glomerular tuft volume (P=0.001, a 94% higher Bowman's space volume (P=0.003, a 33% higher cross-sectional area of the proximal tubular epithelium (P=0.02 and a 54% higher cross-sectional area of the proximal tubular lumen (P=0.01. The nuclei number per proximal tubular profile was similar in both groups, suggesting that the increase in tubular volume is due to hypertrophy and not to hyperplasia. CONCLUSIONS: Obesity-related glomerular hyperfiltration is associated with proximal tubular epithelial hypertrophy and increased glomerular and tubular urinary space volume in subjects with proteinuria. The expanded glomerular and urinary space is probably a direct consequence of glomerular hyperfiltration. These effects may be involved in the pathogenesis of obesity

  13. Determination of normal value of glomerular size in Chinese adults by different measurement methods.

    Science.gov (United States)

    Cheng, Hong; Dong, Hong-Rui; Lin, Rui-Qi; Sun, Li-Jun; Chen, Yi-Pu

    2012-07-01

      Identification of glomerulomegaly is a prerequisite for diagnosis of obesity-related glomerulopathy, so measurement of glomerular size is of critical importance.   A total 100 cases pathologically diagnosed as minor glomerular abnormalities or thin basement membrane nephropathy with normal body mass index and blood glucose level were selected as the normal value measurement group of glomerular size. The mean value of diameters of capillary tuft on the glomerular maximum profile was determined using the direct method and indirect method with the Motic Med 6.0 digital medical image analysis system. Meanwhile, 80 cases of different glomerular disease with normal body mass index and blood glucose level were also collected. Their glomerular diameters were measured and compared with those in the normal value measurement group.   The measurement results showed that gender and age had no effects on glomerular diameter. The normal value ranges of the diameter on glomerular maximum profile were as follows. (i) Pole-containing glomerulus (the glomerulus with vascular pole or/and urinary pole): direct method, 101.3-184.9 µm; indirect method, 100.3-183.5 µm. (ii) Pole-containing glomerulus plus non-pole glomerulus (the glomerulus without poles, the maximum profile of which was larger than that in the smallest pole-containing glomerulus): direct method, 108.3-185.9 µm; indirect method, 107.4-185.4 µm. The glomerular diameters of the 80 cases with different glomerular disease were all within the aforementioned normal value ranges.   Both methods used in the present study are feasible to measure the glomerular diameter and the normal value range of glomerular diameter in Chinese adults is established. © 2012 The Authors. Nephrology © 2012 Asian Pacific Society of Nephrology.

  14. Determination of Glomerular Filtration Rate by Using Gamma camera

    International Nuclear Information System (INIS)

    Amer, M.; Salim, D.

    2007-01-01

    Glomerular filtration rate (GFR) is a commonly accepted standard measure of renal function. It is routinely measured using tracers that are cleared exclusively by glomerular filtration. The aim of this study was to apply new nuclear medicine technique based on direct determination of clearance of a radioactive tracer provided that all the uptake compartments of the radioactive tracer should be included in the field of the view of the gamma camera. A total of 10 men and 7 women range from 27 to 64 years old were studied using dual head gamma camera. The data for clearance calculation comprises : (1) a transmission scan of part of the body using water phantom with a uniform distribution of the radioisotope , (2) the background corrected activity curves in the anterior and posterior views over all uptake compartments following the injection of radioactive tracer, and (3) the activity of radioactive tracer in two blood samples drawn during the examination. The results for GFR above 30 ml min -1 , the regression line of GFR by using simplified multiple sample method versus GFR in gamma camera method were not significantly different from the line of identity. The reliability of the gamma camera method was about 16%, 12 % and 8% for GFR values of 30, 60 and 100 ml min-1. Therefore, the reliability of the gamma camera and the simplified multiple sample method for prediction of GFR were almost the same.

  15. Pathophysiology of glomerular hyperfiltration in diabetes. Part II

    Directory of Open Access Journals (Sweden)

    Claudio Mascheroni

    2014-12-01

    Full Text Available Glomerular hyperfiltration (GH in diabetic renal disease is a complex hemodynamic phenomenon that occurs early in the course of the disease and most likely has associated with poor prognosis with respect to the development of microalbuminuria and overt diabetic nephropathy. The factors involved in its pathophysiology are multiple and include the diabetic milieu and the effects of several humoral factors such as nitric oxide, prostaglandins, renin angiotensin aldosterone system, atrial natriuretic peptide, reactive oxygen species and other humoral and growth factors that act basically causing or enhancing the afferent arteriole vasodilation (AA or vasoconstriction over the efferent arteriola, all considered primary vascular factors. However, these factors could not entirely explain other observed abnormalities that include primary tubular abnormalities such as increased reabsorption in the proximal tubule probably influenced by renal growth and cotransporter SGLT2 upregulation. This increased proximal reabsorption elicit a lower solute delivery to the dense macula, which would be incompatible with glomerulotubular balance function, but would with actions mediated by tubuloglomerular feedback (TGF that would sense low NaCl concentration at the MD, deactivating TGF and producing AA vasodilation, thereby increasing the glomerular filtration rate (GFR and renal plasma flow (RPF, characteristic of the GH process.

  16. Characterization of glomerular extracellular matrix by proteomic analysis of laser captured microdissected glomeruli

    Science.gov (United States)

    Hobeika, Liliane; Barati, Michelle T.; Caster, Dawn J.; McLeish, Kenneth R.; Merchant, Michael L.

    2016-01-01

    Abnormal extracellular matrix (ECM) remodeling is a prominent feature of many glomerular diseases and is a final common pathway of glomerular injury. However, changes in ECM composition accompanying disease-related remodeling are unknown. The physical properties of ECM create challenges for characterization of composition using standard protein extraction techniques, as the insoluble components of ECM are frequently discarded and many ECM proteins are in low abundance compared to other cell proteins. Prior proteomic studies defining normal ECM composition used a large number of glomeruli isolated from human kidneys retrieved for transplantation or by nephrectomy for cancer. Here we examined the ability to identify ECM proteins by mass spectrometry using glomerular sections compatible with that available from standard renal biopsy specimens. Proteins were classified as ECM by comparison to the Matrisome database and previously identified glomerular ECM proteins. Optimal ECM protein identification resulted from sequential decellularization and protein extraction of 100 human glomerular sections isolated by laser capture microdissection from either frozen or formalin fixed paraffin embedded tissue. In total, 147 ECM proteins were identified, including the majority of structural and GBM proteins previously identified along with a number of matrix and glomerular basement membrane proteins not previously associated with glomeruli. Thus, our study demonstrates the feasibility of proteomic analysis of glomerular ECM from retrieved glomerular sections isolated from renal biopsy tissue and expands the list of known ECM proteins in glomeruli. PMID:27988214

  17. Nucleosomes and histones are present in glomerular deposits in human lupus nephritis

    NARCIS (Netherlands)

    vanBruggen, MCJ; Kramers, C; Walgreen, B; Elema, JD; Kallenberg, CGM; vandenBorn, J; Smeenk, RJT; Assmann, KJM; Muller, S; Monestier, M; Berden, JHM

    Background. Recently we showed that antinuclear autoantibodies complexed to nucleosomes can bind to heparan sulphate (HS) in the glomerular basement membrane (GEM) via the histone part of the nucleosome. Histones have been identified in glomerular deposits in human and murine lupus nephritis. In

  18. Impaired autoregulation of glomerular filtration rate in type 1 (insulin-dependent) diabetic patients with nephropathy

    DEFF Research Database (Denmark)

    Parving, H H; Kastrup, Helge; Smidt, U M

    1984-01-01

    served as controls. Renal function was assessed by glomerular filtration rate (single bolus 51Cr-EDTA technique) and urinary albumin excretion rate (radial immunodiffusion). The study was performed twice within 2 weeks, with the subjects receiving an intravenous injection of either clonidine (225...... arterial blood pressure in all three groups (16-18 mmHg). While glomerular filtration rate and urinary albumin excretion rate remained unchanged in both control groups after clonidine injection, glomerular filtration rate diminished from 78 to 71 ml/min per 1.73 m2 (p les than 0.01), and urinary albumin...... excretion declined from 1707 to 938 micrograms/min (p less than 0.01) in the patients with diabetic nephropathy. Our results suggest that an intrinsic vascular (arteriolar) mechanism underlying the normal autoregulation of glomerular filtration rate, i.e. the relative constancy of glomerular filtration rate...

  19. B Cell Depletion: Rituximab in Glomerular Disease and Transplantation

    Directory of Open Access Journals (Sweden)

    S. Marinaki

    2013-12-01

    Full Text Available B cells play a central role in the pathogenesis of many autoimmune diseases. Selective targeting can be achieved with the use of the monoclonal antibody rituximab. In addition to being a drug for non-Hodgkin's lymphoma, rituximab is also an FDA-approved treatment for refractory rheumatoid arthritis and, since recently, ANCA vasculitis. It has shown efficacy in many autoimmune diseases. This review will discuss current evidence and the rationale of the use of rituximab in glomerular diseases, including randomized controlled trials. The focus will be on the use of rituximab in idiopathic membranous nephropathy, systemic lupus erythematosus and ANCA-associated vasculitis. The emerging role of rituximab in renal transplantation, where it seems to be important for the desensitization protocols for highly sensitized patients as well as for the preconditioning of ABO-incompatible recipients and the treatment of antibody-mediated rejection, will also be addressed.

  20. Glomerular diseases and cancer: evaluation of underlying malignancy.

    Science.gov (United States)

    Pani, Antonello; Porta, Camillo; Cosmai, Laura; Melis, Patrizia; Floris, Matteo; Piras, Doloretta; Gallieni, Maurizio; Rosner, Mitchell; Ponticelli, Claudio

    2016-04-01

    Onconephrology is an emerging medical subspecialty focused on the numerous interconnections between cancer and kidney diseases. Patient with malignancies commonly experience kidney problems including acute kidney injury, tumor lysis syndrome, fluid and electrolyte disorders and chronic kidney disease, often as a consequence of the anti-cancer treatment. Conversely, a number of glomerulopathies, tubulopathies and vascular renal diseases can early signal the presence of an underlying cancer. Furthermore, the administration of immunosuppressive drugs, especially cytotoxic drugs and calcineurin inhibitors, may strongly impair the immune response increasing the risk of cancer. The objective of this review article is to: (i) discuss paraneoplastic glomerular disease, (ii) review cancer as an adverse effect of immunosuppressive agents used to treat glomerulopathies, and (iii) in the absence of international approved guidelines, propose a screening program based on expert opinion aimed at guiding nephrologists to early detect malignancies during their clinical practice.

  1. Glomerular and Tubular Damage Markers in Individuals with Progressive Albuminuria

    Science.gov (United States)

    Nauta, Ferdau L.; Scheven, Lieneke; Meijer, Esther; van Oeveren, Wim; de Jong, Paul E.; Bakker, Stephan J.L.

    2013-01-01

    Summary Background and objectives Albuminuria is associated with risk for renal and cardiovascular disease. It is difficult to predict which persons will progress in albuminuria. This study investigated whether assessment of urinary markers associated with damage to different parts of the nephron may help identify individuals that will progress in albuminuria. Design, setting, participants, & measurements Individuals were selected from a prospective community-based cohort study with serial follow-up and defined as “progressors” if they belonged to the quintile of participants with the most rapid annual increase in albuminuria, and reached an albuminuria ≥150 mg/d during follow-up. Patients with known renal disease or macroalbuminuria at baseline were excluded. Each progressor was matched to two control participants, based on baseline albuminuria, age, and sex. Furthermore, damage markers were measured in a separate set of healthy individuals. Results After a median follow-up of 8.6 years, 183 of 8394 participants met the criteria for progressive albuminuria. Baseline clinical characteristics were comparable between progressors and matched controls (n=366). Both had higher baseline albuminuria than the overall population. Urinary excretion of the glomerular damage marker IgG was significantly higher in progressors, whereas urinary excretion of proximal tubular damage markers and inflammatory markers was lower in these individuals compared with controls. Healthy individuals (n=109) had the lowest values for all urinary damage markers measured. Conclusions These data suggest that albuminuria associated with markers of glomerular damage is more likely to progress, whereas albuminuria associated with markers of tubulointerstitial damage is more likely to remain stable. PMID:23539232

  2. Glomerular diseases associated with HBV and HCV infection

    Directory of Open Access Journals (Sweden)

    Boriana Kiperova

    2014-03-01

    Full Text Available Hepatitis B and C viruses are human pathogens of major significance. Their extrahepatic manifestations are global health problem. HBV is a well-known cause of membranous nephropathy, membranoproliferative GN and IgA nephropathy, frequently in Asian populations. Polyarteritis nodosa is a rare, but serious systemic complication of chronic HBV. Immunosuppressive therapy in HBV-related GN is not recommended. Interferon alpha treatment produces sustained remission of porteinuria, often associated with clearance of HBeAg and/or HBsAg, however, it has many side effects. Compared to interferon, nucleos(tide analogues offer some advantages. These antiviral agents suppress HBV replication through their inhibitory effect on viral DNA polymerase. They have convenient administration and high tolerability. Lamivudine is well tolerated and safe in long-term studies, but the resistance of HBV is an escalating problem. The resistance to newer polymerase inhibitors Entecavir and Tenofovir is significantly lower. Hepatitis C virus causes cryoglobulinemia-mediated glomerulonephritis and other immune complex forms of GN. The renal manifestations are usually associated with long-lasting HCV infection. HCV glomerular disease is more frequent in adult males, and often leads to chronic renal insufficiency. The first line treatment in patients with mild to moderate clinical and histological kidney damage is the antiviral therapy with pegylated INF alpha and ribavirin. In case of severe HCV-associated cryoglobulinemic GN - nephrotic syndrome, nephritic syndrome and/or progressive renal failure, high activity score of glomerulonephritis on light microscopy, the initial treatment might consist of sequential administration of antiviral and immunosuppressive agents (corticosteroids, cyclophosphamide and plasma exchange, or rituximab. The treatment of HCV-related glomerular disease is still under debate and based on scant experimental evidence. Large randomized and controlled

  3. Glomerular damage as a predictor of renal allograft loss

    Directory of Open Access Journals (Sweden)

    G. Moscoso-Solorzano

    2010-06-01

    Full Text Available Interstitial fibrosis and tubular atrophy (IF/TA are the most common cause of renal graft failure. Chronic transplant glomerulopathy (CTG is present in approximately 1.5-3.0% of all renal grafts. We retrospectively studied the contribution of CTG and recurrent post-transplant glomerulopathies (RGN to graft loss. We analyzed 123 patients with chronic renal allograft dysfunction and divided them into three groups: CTG (N = 37, RGN (N = 21, and IF/TA (N = 65. Demographic data were analyzed and the variables related to graft function identified by statistical methods. CTG had a significantly lower allograft survival than IF/TA. In a multivariate analysis, protective factors for allograft outcomes were: use of angiotensin-converting enzyme inhibitor (ACEI; hazard ratio (HR = 0.12, P = 0.001, mycophenolate mofetil (MMF; HR = 0.17, P = 0.026, hepatitis C virus (HR = 7.29, P = 0.003, delayed graft function (HR = 5.32, P = 0.016, serum creatinine ≥1.5 mg/dL at the 1st year post-transplant (HR = 0.20, P = 0.011, and proteinuria ≥0.5 g/24 h at the 1st year post-transplant (HR = 0.14, P = 0.004. The presence of glomerular damage is a risk factor for allograft loss (HR = 4.55, P = 0.015. The presence of some degree of chronic glomerular damage in addition to the diagnosis of IF/TA was the most important risk factor associated with allograft loss since it could indicate chronic active antibody-mediated rejection. ACEI and MMF were associated with better outcomes, indicating that they might improve graft survival.

  4. Barrier Systems

    NARCIS (Netherlands)

    Heteren, S. van

    2015-01-01

    Barrier-system dynamics are a function of antecedent topography and substrate lithology, Relative sea-level (RSL) changes, sediment availability and type, climate, vegetation type and cover, and various aero- and hydrodynamic processes during fair-weather conditions and extreme events. Global change

  5. A ventral glomerular deficit in Parkinson's disease revealed by whole olfactory bulb reconstruction.

    Science.gov (United States)

    Zapiec, Bolek; Dieriks, Birger V; Tan, Sheryl; Faull, Richard L M; Mombaerts, Peter; Curtis, Maurice A

    2017-10-01

    Olfactory dysfunction is common in Parkinson's disease and is an early symptom, but its pathogenesis remains poorly understood. Hindering progress in our mechanistic understanding of olfactory dysfunction in Parkinson's disease is the paucity of literature about the human olfactory bulb, both from normal and Parkinson's disease cases. Qualitatively it is well established that the neat arrangement of the glomerular array seen in the mouse olfactory bulb is missing in humans. But rigorous quantitative approaches to describe and compare the thousands of glomeruli in the human olfactory bulb are not available. Here we report a quantitative approach to describe the glomerular component of the human olfactory bulb, and its application to draw statistical comparisons between olfactory bulbs from normal and Parkinson's disease cases. We subjected horizontal 10 µm sections of olfactory bulbs from six normal and five Parkinson's disease cases to fluorescence immunohistochemistry with antibodies against vesicular glutamate transporter-2 and neural cell adhesion molecule. We scanned the immunostained sections with a fluorescence slide scanner, segmented the glomeruli, and generated 3D reconstructions of whole olfactory bulbs. We document the occurrence of atypical glomerular morphologies and glomerular-like structures deep in the olfactory bulb, both in normal and Parkinson's disease cases. We define a novel and objective parameter: the global glomerular voxel volume, which is the total volume of all voxels that are classified immunohistochemically as glomerular. We find that the global glomerular voxel volume in Parkinson's disease cases is half that of normal cases. The distribution of glomerular voxels along the dorsal-ventral dimension of the olfactory bulb in these series of horizontal sections is significantly altered in Parkinson's disease cases: whereas most glomerular voxels reside within the ventral half of olfactory bulbs from normal cases, glomerular voxels are

  6. Assessment of glomerular filtration rate and effective renal plasma flow in cystic fibrosis

    International Nuclear Information System (INIS)

    Spino, M.; Chai, R.P.; Isles, A.F.; Balfe, J.W.; Brown, R.G.; Thiessen, J.J.; MacLeod, S.M.

    1985-01-01

    A study was conducted to examine renal function in 10 healthy control subjects and eight patients with cystic fibrosis in stable condition. Sequential bolus injections of /sup 99m/Tc-DTPA and 125 I-OIH were administered to assess glomerular filtration rate and effective renal plasma flow, respectively. Blood was subsequently collected for 3 hours, and urine for 24 hours. Renal clearances of both radioisotope markers were virtually identical in patients and controls. Inasmuch as neither glomerular filtration rate nor effective renal plasma flow was enhanced in patients with cystic fibrosis, increased clearance of drugs in these patients is unlikely to be the result of enhanced glomerular filtration or tubular secretion

  7. Changing the concepts of immune-mediated glomerular diseases through proteomics.

    Science.gov (United States)

    Caster, Dawn J; Hobeika, Liliane; Klein, Jon B; Powell, David W; McLeish, Kenneth R

    2015-12-01

    Standard classification of glomerular diseases is based on histopathologic abnormalities. The recent application of proteomic technologies has resulted in paradigm changes in the understanding and classification of idiopathic membranous nephropathy and membranoproliferative glomerulonephritis. Those examples provide evidence that proteomics will lead to advances in understanding of the molecular basis of other glomerular diseases, such as lupus nephritis. Proof of principle experiments show that proteomics can be applied to patient renal biopsy specimens. This viewpoint summarizes the advances in immune-mediated glomerular diseases that have relied on proteomics, and potential future applications are discussed. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Physiology Lab Demonstration: Glomerular Filtration Rate in a Rat.

    Science.gov (United States)

    Hinojosa-Laborde, Carmen; Jespersen, Brian; Shade, Robert

    2015-07-26

    Measurements of glomerular filtration rate (GFR), and the fractional excretion of sodium (Na) and potassium (K) are critical in assessing renal function in health and disease. GFR is measured as the steady state renal clearance of inulin which is filtered at the glomerulus, but not secreted or reabsorbed along the nephron. The fractional excretion of Na and K can be determined from the concentration of Na and K in plasma and urine. The renal clearance of inulin can be demonstrated in an anesthetized animal which has catheters in the femoral artery, femoral vein and bladder. The equipment and supplies used for this procedure are those commonly available in a research core facility, and thus makes this procedure a practical means for measuring renal function. The purpose of this video is to demonstrate the procedures required to perform a lab demonstration in which renal function is assessed before and after a diuretic drug. The presented technique can be utilized to assess renal function in rat models of renal disease.

  9. American Society of Nephrology quiz and questionnaire 2014: glomerular diseases.

    Science.gov (United States)

    Bomback, Andrew S; Perazella, Mark A; Choi, Michael J

    2015-04-07

    The Nephrology Quiz and Questionnaire remains an extremely popular session for attendees of the Annual Kidney Week Meeting of the American Society of Nephrology. Once again, the conference hall was overflowing with audience members and eager quiz participants. Topics covered by the expert discussants included electrolyte and acid-base disorders, glomerular disease, ESRD/dialysis, and transplantation. Complex cases representing each of these categories along with single best answer questions were prepared and submitted by the panel of experts. Before the meeting, program directors of United States nephrology training programs and nephrology fellows answered the questions through an internet-based questionnaire. During the live session, members of the audience tested their knowledge and judgment on a series of case-oriented questions that were prepared and discussed by the experts. They compared their answers in real time using audience response devices with the answers of the nephrology fellows and training program directors. The correct and incorrect answers were then discussed after the audience responses, and the results of the questionnaire were displayed. As always, the audience, lecturers, and moderators enjoyed this educational session. This article recapitulates the session and reproduces its educational value for the readers of CJASN. Enjoy the clinical cases and expert discussions. Copyright © 2015 by the American Society of Nephrology.

  10. GLOMERULAR FILTRATION RATE AS INDICATOR OF RENAL FAILURE IN DIABETICS

    Directory of Open Access Journals (Sweden)

    Saša Đurišić

    2007-10-01

    Full Text Available Diabetic nephropathy is a progredient disease which leads to the end stage renal disease and stands for a leading cause of its development in western countries. About one third of patients included in the dialysis program or transplanation program in the USA are diabetics. The aim of the paper was to analyze the degree of renal failure in diabetics by measuring the glomerular filtration rate (GFR and to show the advantages of this method comparing with serum creatinine levels. Total numbers of 23 patients with diabetes mellitus type 1 or type 2 were anlyzed and controlled monthly during 6 months. Average GFR in the examined patients was 53,23±15,48 mL/min/1.73m2. Obtained values for GFR according to CKD Care and ESRD recommendations showed that the great number of diabetics had stage 3 renal failure while stages 1 and 5 were not registered. GFR is an important marker for diagnostics and estimation of renal failure progression in diabetics. Bearing in mind this facts, periodical controls in diabetics must be suplemented by measuring GFR, so as to perform early identification and determination of severity of renal failure. Measuring of lipoprotein levels and determination of glycemic profile must be done according to the National recommendations twice a year. Besides adequate glycoregulation, diabetics need statins therapy and antyhipertensive tratment with ACE inhibitors.

  11. 125I iothalamate an ideal marker for glomerular filtration

    International Nuclear Information System (INIS)

    Odlind, B.; Haellgren, R.S.; Sohtell, M.; Lindstroem, B.

    1985-01-01

    The triiodinated angiographic contrast medium, iothalamate (usually labelled 125 I), has been used extensively as a marker for glomerular filtration. The authors have studied the renal handling of 125 I iothalamate (IOT) in vivo and in vitro in several species. In renal cortical slices from chicken, rabbit, rat, and monkey, the tissue-to-medium ratio of IOT was twice that of 51 Cr-EDTA (EDTA) at 37 degrees C; a difference that was abolished at 0 degree C and markedly reduced by added o-iodohippurate or iodipamide. In five chickens the steady-state renal clearance of IOT (CIOT) was twice that of EDTA (CEDTA) or 3 H inulin (C1); a difference that was abolished by administration of 100 mg/kg/hr of novobiocin, an organic anion transport inhibitor. CEDTA was similar to C1 before as well as after transport inhibition. Utilizing the Sperber technique the mean apparent tubular excretion fraction (ATEF) of IOT was 8%, while that of EDTA was 1%. After novobiocin coinfusion (new steady-state) ATEFIOT was significantly reduced and not different from that of EDTA (-1%). In the same animals the total urinary recovery of IOT was 84 and 57% before and after novobiocin, respectively, while corresponding values for EDTA was unchanged by the inhibitor. In seven rats the renal extraction of IOT was reduced from 29 to 17% by coinfusion of probenecid (5 mg/kg/hr). Corresponding extractions were 82 to 34% and 22% (unchanged) for PAH and EDTA, respectively

  12. Value of electron microscopy in the diagnosis of glomerular diseases.

    Science.gov (United States)

    Darouich, Sihem; Goucha, Rym Louzir; Jaafoura, Mohamed Habib; Moussa, Fatma Ben; Zekri, Semy; Maiz, Hédi Ben

    2010-04-01

    To evaluate the contribution of electron microscopy to the final diagnosis of glomerulopathies, the authors established a prospective study during the first semester of 2006. A total of 52 kidney biopsies were performed with 3 samples for light microscopy, immunofluorescence, and electron microscopy. Among these renal biopsies, only 20 were examined with electron microscopy because the diagnosis made on the basis of conventional methods had remained unclear or doubtful. In 18 cases, electron microscopy was undertaken for the investigation of primary kidney disease. The 2 remaining cases were transplant biopsies. In this series of 20 patients, there were 3 children with an average age of 9 years and 17 adults with an average age of 35.5 years. Fifteen patients (75%) were nephrotic. The study revealed that electron microscopy was essential for diagnosis in 8 cases (40%) and was helpful in 12 cases (60%). In conclusion, the results showed that the ultrastructural study provides essential or helpful information in many cases of glomerular diseases, and therefore electron microscopy should be considered an important tool of diagnostic renal pathology. As was recommended, it is important to reserve renal tissue for ultrastructural study unless electron microscopy can be routinely used in all biopsies. Thus, this technique could be performed wherever a renal biopsy has to be ultrastructurally evaluated.

  13. American Society of Nephrology Quiz and Questionnaire 2015: Glomerular Diseases.

    Science.gov (United States)

    Bomback, Andrew S; Perazella, Mark A; Choi, Michael J

    2016-05-06

    The Nephrology Quiz and Questionnaire remains an extremely popular session for attendees of the annual Kidney Week meeting of the American Society of Nephrology. Once again, the conference hall was overflowing with audience members and eager quiz participants. Topics covered by the expert discussants included electrolyte and acid-base disorders, glomerular disease, ESRD/dialysis, and kidney transplantation. Complex cases representing each of these categories, along with single-best-answer questions, were prepared and submitted by the panel of experts. Before the meeting, training program directors of United States nephrology fellowship programs and nephrology fellows answered the questions through an Internet-based questionnaire. During the live session, members of the audience tested their knowledge and judgment on a series of case-oriented questions prepared and discussed by the experts. They compared their answers in real time using their cell phones with a special app with the answers of the nephrology fellows and training program directors. The correct and incorrect answers were then discussed after the results of the questionnaire were displayed. As always, the audience, lecturers, and moderators enjoyed this educational session. This article recapitulates the session and reproduces its educational value for Clinical Journal of the American Society of Nephrology readers. Enjoy the clinical cases and expert discussions. Copyright © 2016 by the American Society of Nephrology.

  14. Basement membrane proteoglycans in glomerular morphogenesis: chondroitin sulfate proteoglycan is temporally and spatially restricted during development

    DEFF Research Database (Denmark)

    McCarthy, K J; Bynum, K; St John, P L

    1993-01-01

    basement membrane (GBM) but present in other basement membranes of the nephron, including collecting ducts, tubules, Bowman's capsule, and the glomerular mesangium. In light of this unique pattern of distribution and of the complex histoarchitectural reorganization occurring during nephrogenesis...

  15. Morphological aspects of the rat kidney preserved by cold storage. I. Glomerular morphometric changes.

    Science.gov (United States)

    Neagu, S; Chirculescu, A R; Ranga, V; Popescu, F

    1983-01-01

    The absolute density of glomeruli in the microscopic field was determined in the rat kidney preserved by cold storage for 24, 48, 72 and 96 hrs in two different media: Sacks (hyperosmolar electrolytic solution of intracellular type) and Plasmagel (gelatin solution 4%). Progressive, statistically significant (p less than 0.01) decrease of glomerular density at 24 and 48 hrs was followed by return to initial values at 96 hrs. Decrease of the glomerular density was greater with Plasmagel.

  16. [Effect of collagenase on the permeability of the glomerular basement membrane in the rat kidney].

    Science.gov (United States)

    Laloi, C; Geloso-Meyer, A; Cheignon, M; Schaeverbeke, J

    1981-03-16

    Recently, several authors have emphasized the role of negative sites located in th laminae rarae of the glomerular basement membrane (GBM), in restricting glomerular permeability to anionic macromolecules. In this work, we point out that ultrafiltration properties involve integrity of the GBM. Indeed after intravenous perfusion of bacterian collagenase, anionic ferritin permeates the GBM though negative site distribution (as shown by fixation of colloidal iron) is unaffected.

  17. Olfactory aversive conditioning alters olfactory bulb mitral/tufted cell glomerular odor responses

    Directory of Open Access Journals (Sweden)

    Max L Fletcher

    2012-03-01

    Full Text Available The anatomical organization of receptor neuron input into the olfactory bulb (OB allows odor information to be transformed into an odorant-specific spatial map of mitral/tufted cell glomerular activity at the upper level of the olfactory bulb. In other sensory systems, neuronal representations of stimuli can be reorganized or enhanced following learning. While the mammalian OB has been shown to undergo experience-dependent plasticity at the glomerular level, it is still unclear if similar representational change occurs within mitral/tufted cell glomerular odor representations following learning. To address this, odorant-evoked glomerular activity patterns were imaged in mice expressing a GFP-based calcium indicator (GCaMP2 in OB mitral/tufted cells. Glomerular odor responses were imaged before and after olfactory associative conditioning to aversive foot shock. Following conditioning, we found no overall reorganization of the glomerular representation. Training, however, did significantly alter the amplitudes of individual glomeruli within the representation in mice in which the odor was presented together with foot shock. Further, the specific pairing of foot shock with odor presentations lead to increased responses primarily in initially weakly activated glomeruli. Overall, these results suggest that associative conditioning can enhance the initial representation of odors within the olfactory bulb by enhancing responses to the learned odor in some glomeruli.

  18. Measurement of glomerular filtration rate in the conscious rat.

    Science.gov (United States)

    Pestel, Sabine; Krzykalla, Volker; Weckesser, Gerhard

    2007-01-01

    Glomerular filtration rate (GFR) is an important parameter for studying drug-induced impairments on renal function in rats. The GFR is calculated from the concentration of creatinine and blood urea nitrogen (BUN) in serum and in urine, respectively. Following current protocols serum and urine samples must be taken from the same animal. Thus, in order to determine time-dependent effects it is necessary to use for each time point one separated group of animals. We developed a statistical test which allows analyzing the GFR from two different groups of animals: one used for repeated serum and the other one used for repeated urine analysis. Serum and urine samples were taken from two different sets of rats which were otherwise treated identically, i.e. drug doses, routes of administration (per os or per inhalation) and tap water loading. For each dose group GFR mean, standard deviation and statistical analysis to identify differences between the dose groups were determined. After determination of the optimal time points for measurements, the effect on GFR of the three reference compounds, furosemide, hydrochlorothiazide and formoterol, was calculated. The results showed that the diuretic drugs furosemide and hydrochlorothiazide decreased the GFR and the antidiuretic drug formoterol increased the GFR, as counter regulation on urine loss or urine retention, respectively. A mathematical model and the corresponding algorithm were developed, which can be used to calculate the GFR, and to test for differences between groups from two separated sets of rats, one used for urine, and the other one for serum analysis. This new method has the potential to reduce the number of animals needed and to improve the quality of data generated from various groups of animals in renal function studies.

  19. /sup 125/I iothalamate an ideal marker for glomerular filtration

    Energy Technology Data Exchange (ETDEWEB)

    Odlind, B.; Haellgren, R.S.; Sohtell, M.; Lindstroem, B.

    1985-01-01

    The triiodinated angiographic contrast medium, iothalamate (usually labelled /sup 125/I), has been used extensively as a marker for glomerular filtration. The authors have studied the renal handling of /sup 125/I iothalamate (IOT) in vivo and in vitro in several species. In renal cortical slices from chicken, rabbit, rat, and monkey, the tissue-to-medium ratio of IOT was twice that of /sup 51/Cr-EDTA (EDTA) at 37 degrees C; a difference that was abolished at 0 degree C and markedly reduced by added o-iodohippurate or iodipamide. In five chickens the steady-state renal clearance of IOT (CIOT) was twice that of EDTA (CEDTA) or /sup 3/H inulin (C1); a difference that was abolished by administration of 100 mg/kg/hr of novobiocin, an organic anion transport inhibitor. CEDTA was similar to C1 before as well as after transport inhibition. Utilizing the Sperber technique the mean apparent tubular excretion fraction (ATEF) of IOT was 8%, while that of EDTA was 1%. After novobiocin coinfusion (new steady-state) ATEFIOT was significantly reduced and not different from that of EDTA (-1%). In the same animals the total urinary recovery of IOT was 84 and 57% before and after novobiocin, respectively, while corresponding values for EDTA was unchanged by the inhibitor. In seven rats the renal extraction of IOT was reduced from 29 to 17% by coinfusion of probenecid (5 mg/kg/hr). Corresponding extractions were 82 to 34% and 22% (unchanged) for PAH and EDTA, respectively.

  20. A pitfall of glomerular sieving: profibrotic and matrix proteins derive from the Bowman's capsule and not the glomerular tuft in rats with renovascular hypertension.

    Science.gov (United States)

    Steinmetz, O M; Panzer, U; Fehr, S; Meyer-Schwesinger, C; Stahl, R A K; Wenzel, U O

    2007-10-01

    The glomeruli in the non-clipped kidney of rats with 2-kidney, 1-clip hypertension are a classical model for studying the mechanisms of glomerular injury. In the present study, we compared the glomerular expression of PAI-1 and collagen I alpha1 mRNA from glomeruli isolated by the classic technique of sieving with the recently developed technique of tissue laser microdissection. For quantification of mRNA from both methods, real-time PCR was used. Real-time PCR revealed a 9.0 +/- 1.3- and a 7.1 +/- 0.2-fold induction of PAI-1 and collagen I alpha 1, respectively, in the glomeruli from hypertensive rats isolated by sieving. However, in situ hybridization and microdissection revealed that expression of both mRNAs was mainly from the Bowman's capsule and not from the glomerular tuft (10.7 +/- 1.3- and 7.2 +/- 0.6-fold higher induction in whole glomeruli compared with tuft alone). This emphasizes that studies focusing on processes in the mesangium, endothelial cells or podocytes should not rely on glomeruli obtained by sieving. Rather, a technique like the laser microdissection or in situ hybridization should be applied which allows the clear separation of different glomerular and periglomerular compartments.

  1. Glomerular filtration rate, cardiovascular risk factors and insulin resistance Filtrado glomerular, riesgo cardiovascular y resistencia a la insulina

    Directory of Open Access Journals (Sweden)

    Martín R. Salazar

    2009-10-01

    Full Text Available The aim of this paper was to study the estimated glomerular filtration rate (eGFR, its changes with age, and its association with systolic blood pressure (SBP and diastolic BP (DBP, indicators of obesity, dyslipemia, insulin resistance and inflammation on a random population sample. BP, weight, size and waist circumference (WC were recorded at home. Fasting morning blood samples were analysed. The eGFR was calculated with MDRD (eGFR-MDRD, Cockroft-Gault (eGFR-CG adjusted to 1.73 m² and reciprocal of serum creatinine (100/serum cretinine. A total of 1016 individuals, 722 females (41.97 ± 0.66 years old and 294 males (42.06 ± 0.99 years old, completed the laboratory tests. The mean of 100/Scr was 115.13 ± 0.60 (dl/mg, the mean eGFR-CG was 98.48 ± 0.82 ml/min/1.73 m²; the mean eGFR-MDRD was 85.15 ± 0.58 ml/min/1.73 m². The eGFR-MDRD decreased with age and with the number of risk factors in both sexes. The eGFR-MDRD El objetivo fue evaluar en una muestra poblacional aleatoria el filtrado glomerular estimado (FGe, sus cambios con la edad y su asociación con presión arterial sistólica (PAS y diastólica (PAD, indicadores de obesidad, dislipemia, resistencia a la insulina e inflamación. En cada domicilio fueron medidos presión arterial, peso y talla y perímetro de la cintura (PC. Se analizaron muestras de sangre en ayunas y fue calculado el FGe usando las fórmulas de MDRD (FGe-MDRD y Cockroft-Gault (FGe-CG ajustado a 1.73 m², y la inversa de la creatinina sérica (100/CrS. Completaron el protocolo de laboratorio 1016 sujetos, 722 mujeres (41.97 ± 0.66 años y 294 varones (42.06 ± 0.99 años. La media de 100/Crs fue 115.13 ± 0.60 (dl/mg, la del FGe-CG 98.48 ± 0.82 ml/min/1.73 m² y la del FGe-MDRD 85.15 ± 0.58 ml/min/1.73 m² (CI 95% 84.00-86.29. El FGe-MDRD disminuyó con la edad y con el número de factores de riesgo cardiovascular en ambos sexos. La prevalecencia ajustada de FGe-MDRD < 60 ml/min/1.73 m² fue 6.2 por 100

  2. Comparing different estimated glomerular filtration rate equations in assessing glomerular function in children based on creatinine and cystatin C.

    Science.gov (United States)

    Conkar, Seçil; Mir, Sevgi; Karaslan, Fatma Nur; Hakverdi, Gülden

    2018-02-27

    Glomerular filtration rate (GFR) is the best marker used to assess renal function. Estimated GFR (eGFR) equations have been developed, and the ideal formula is still under discussion. We wanted to find the most practical and reliable GFR in eGFR formulas. We compared serum creatinine (Scr)- and cystatin C (cysC)-based eGFR formulas in the literature. We also aimed to determine the suitability and the reliability of cysC for practical use in determining GFR in children. We have enrolled 238 children in the study. Measurement of 24-hour creatinine clearance was compared with eGFR equations which are based on Scr, cysC, and creatinine plus cysC. Of the patients (n = 238), 117 were males (49.2%), and 121 (50.8%) were females with a median age of 9.0 years. The areas under the ROC curves of Counahan-Barratt and Bedside Schwartz were equal and 0.89 (with a 95% CI 0.80-0.97). The areas under the ROC curves were not significantly different in all cystatin C-based eGFR equations. The highest AUC values for differentiating normal vs abnormal renal functions according to CrCl 24 were for the CKiD-cysC and CKiD-Scr-cysC equations. In our study, compared with creatinine-based ones, the cystatin C-based formulas did not show much superiority in predicting eGFR. Still, we think Bedside Schwartz is a good formula to provide ease of use because, in this equation, the constant k is same for all age groups. However, the most valuable equations in determining chronic kidney disease are the CKiD-cysC and CKiD-Scr-cysC equations. © 2018 Wiley Periodicals, Inc.

  3. Dietary fish oil intake: effects on glomerular prostanoid formation, hemodynamics, and proteinuria in nephrotoxic serum nephritis.

    Science.gov (United States)

    Thaiss, F; Schoeppe, W; Germann, P; Stahl, R A

    1990-08-01

    Dietary fish oil intake improves glomerular pathology and proteinuria in murine models of autoimmune disease. We evaluated glomerular prostanoid formation, glomerular hemodynamics, and proteinuria in rats with nephrotoxic serum nephritis (NSN) to test whether this beneficial effect of marine lipids also applies to other animal models of glomerular immune injury. Rats were fed diets (8 weeks) containing either cod liver oil or sunflower oil. NSN was induced with a rabbit anti-rat glomerular basement membrane antiserum. Antibody injection significantly stimulated glomerular thromboxane B2 (TxB2) formation in animals fed cod liver oil and sunflower oil at 2 hours, 24 hours, and 7 days. TxB2 production in glomeruli of sunflower oil rats, however, was five to seven times higher when compared with that in rats fed cod liver oil. The dietary regimen led to a significant decrease of glomerular TxB2 and prostaglandin E2 formation in the animals receiving cod liver oil when compared with those fed sunflower oil. Induction of NSN resulted in a significant fall of inulin clearance (Cin) and paraaminohippurate clearance at 2 hours, 24 hours, and 7 days in both groups. The decrease in Cin at 2 hours was greater in rats fed cod liver oil when compared with animals receiving sunflower oil (p less than 0.02); it was not different, however, at 24 hours and 7 days. Animals with NSN developed proteinuria. There was no difference in protein excretion between rats fed cod liver oil or those fed sunflower oil (days 2 and 7).(ABSTRACT TRUNCATED AT 250 WORDS)

  4. Validation of estimated glomerular filtration rate equations for Japanese children.

    Science.gov (United States)

    Gotoh, Yoshimitsu; Uemura, Osamu; Ishikura, Kenji; Sakai, Tomoyuki; Hamasaki, Yuko; Araki, Yoshinori; Hamda, Riku; Honda, Masataka

    2018-01-25

    The gold standard for evaluation of kidney function is renal inulin clearance (Cin). However, the methodology for Cin is complicated and difficult, especially for younger children and/or patients with bladder dysfunction. Therefore, we developed a simple and easier method for obtaining the estimated glomerular filtration rate (eGFR) using equations and values for several biomarkers, i.e., serum creatinine (Cr), serum cystatin C (cystC), serum beta-2 microglobulin (β 2 MG), and creatinine clearance (Ccr). The purpose of the present study was to validate these equations with a new data set. To validate each equation, we used data of 140 patients with CKD with clinical need for Cin, using the measured GFR (mGFR). We compared the results for each eGFR equation with the mGFR using mean error (ME), root mean square error (RMSE), P 30 , and Bland-Altman analysis. The ME of Cr, cystC, β 2 MG, and Ccr based on eGFR was 15.8 ± 13.0, 17.2 ± 16.5, 15.4 ± 14.3, and 10.6 ± 13.0 ml/min/1.73 m 2 , respectively. The RMSE was 29.5, 23.8, 20.9, and 16.7, respectively. The P 30 was 79.4, 71.1, 69.5, and 92.9%, respectively. The Bland-Altman bias analysis showed values of 4.0 ± 18.6, 5.3 ± 16.8, 12.7 ± 17.0, and 2.5 ± 17.2 ml/min/1.73 m 2 , respectively, for these parameters. The bias of each eGFR equation was not large. Therefore, each eGFR equation could be used.

  5. Pattern of glomerular diseases in oman: A study based on light microscopy and immunofluorescence

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    Nasar Yousuf Alwahaibi

    2013-01-01

    Full Text Available Light microscopy and immunofluorescence play an important part in the final diagnosis of renal biopsy. The aim of this study was to analyze the pattern of various glomerular diseases in Oman. A total of 424 renal biopsies were retrospectively analyzed at the Sultan Qaboos University Hospital between 1999 and 2010. Focal and segmental glomerulosclerosis (FSGS, minimal change disease (MCD, membranous glomerulopathy (MGN and IgA nephropathy were the most common primary glomerular diseases encountered, accounting for 21.2%, 17%, 12.3% and 8.3%, respectively, of all cases. Lupus nephritis was the most common secondary glomerular disease and was the most prevalent among all biopsies, accounting for 30.4% of all biopsies. Amyloidosis was seen in only two cases. The presence of fluorescein isothiocyanatefibrin in all renal cases was low when compared with IgG, IgA, IgM, C3 and C1q markers. In conclusion, based on the findings of this study, lupus nephritis was the most common of all glomerular diseases and FSGS was the most common primary glomerular disease. The importance of fluorescein isothiocyanate-fibrin in the diagnosis of renal biopsy needs to be further investigated.

  6. Estimated glomerular filtration rate function in patients with and without metabolic syndrome

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    María E Lizardo

    2016-06-01

    Full Text Available Introduction: Metabolic syndrome (MS is an independent risk factor, which affects the development of chronic kidney disease, so the glomerular filtration rate (GFR as an indicator of glomerular function in patients with and without MS who attended the outpatient clinic “los Grillitos, sector Caña de Azucar”. Materials and Methods: A comparative, correlational, cross-sectional study was conducted in a non-probability sample of convenience consisting of 60 patients with MS diagnosed according to the criteria Panel ATP III, and 60 apparently healthy individuals, whom the GFR was determined by the Cockcroft-Gault as well as clinical and biochemical parameters for the diagnosis of MS. Results: Out of the total patients evaluated, 37 (30.7% showed alterations that put them in grades G2 and G3 system risk stratification of CKD, of these 18 and 19 corresponded to patients with and without MS respectively. Glomerular Hyperfiltration (> 120 mil / min it was found in both groups 28 (46.7% and 24 (40% cases of patients with and without MS respectively. The glomerular function was strongly correlated with abdominal obesity and high levels of stress arterial. As for the number of criteria and its relationship to the level of kidney damage present, not a firm to increase the latter with respect to the first (p=0.385 trend was observed. Conclusion: The change in the glomerular function is not directly related to the MS but with its components, specifically abdominal obesity and hypertension.

  7. Renal glomerular lesions in unselected patients with cirrhosis undergoing orthotopic liver transplantation.

    Science.gov (United States)

    Axelsen, R A; Crawford, D H; Endre, Z H; Lynch, S V; Balderson, G A; Strong, R W; Fleming, S J

    1995-07-01

    Renal biopsies were obtained from 23 patients at the time of orthotopic liver transplantation. Twelve biopsies showed minor glomerular abnormalities, 2 exhibited IgA nephropathy and one showed mesangiocapillary glomerulonephritis type I. The remaining 8 patients had glomerular lesions diagnosed as hepatic glomerulosclerosis (HGS). Immunofluorescence, available in 6 of the 8 biopsies with HGS, revealed granular deposits of immunoglobulins and complement in glomerular capillary walls and/or the mesangium. IgA was seen in 5 biopsies with HGS, but the staining for this protein was no more intense than that for the other immunoglobulins in 4 of these. Electron microscopy in HGS revealed partial mesangial interposition, hypertophy of mesangial and endothelial cells, granular material in a widened subendothelial space, slender projections of endothelial cytoplasm extending into the subendothelial space, and clusters of vesicles in the mesangium and glomerular capillary walls. These ultrastructural abnormalities have not hitherto been reported as a group of associated pathological changes. The renal biopsies were obtained from patients with advanced hepatic disease not selected because of urinary abnormalities or renal dysfunction. The frequency of lesions in this group of patients therefore probably reflects the true incidence of glomerular lesions in cirrhosis and related conditions. Progressive decline in renal function was not observed in any patient during follow up which ranged from 11 days to 55 mths.

  8. Childhood primary glomerular diseases in the western region of Saudi Arabia

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    Jalalah Sawsan

    2009-01-01

    Full Text Available We report our institute experience on primary glomerular disease in children in the western region of Saudi Arabia over the last 18 years (1988 to 2006. A total of 169 cases were identified as primary glomerular diseases in children and adolescent with age range from first year of life till 18 years. Minimal change disease and focal segmental glomerulosclerosis were the com-monly encountered primary glomerular diseases (20.1%and 19.5% respectively, mesangioprolifera-tive glomerulonephritis IgM nephropathy (14.8%, IgA nephropathy (10.7%, postinfectious glome-rulonephritis (9.5%, membranous glomerulonephritis (7.1%, membranoproliferative glomerulone-phritis (5.9% and mesangioproliferative glomerulonephritis with negative immunofluorescence (5.9%. The less frequently encountered primary glomerular diseases were congenital nephritic syn-drome Finnish type (2.4%, Alport syndrome (2.4%, dense deposit disease (1.2%, and mesangio-proliferative glomerulonephritis with IgG positive (0.6%. We concluded that minimal change di-sease and focal segmental glomerulosclerosis are the most common primary glomerular disorder en-countered in children in our series and with similar age distribution.

  9. Applicability of estimating glomerular filtration rate equations in pediatric patients: comparison with a measured glomerular filtration rate by iohexol clearance.

    Science.gov (United States)

    Deng, Fang; Finer, Gal; Haymond, Shannon; Brooks, Ellen; Langman, Craig B

    2015-03-01

    Estimating glomerular filtration rate (eGFR) has become popular in clinical medicine as an alternative to measured GFR (mGFR), but there are few studies comparing them in clinical practice. We determined mGFR by iohexol clearance in 81 consecutive children in routine practice and calculated eGFR from 14 standard equations using serum creatinine, cystatin C, and urea nitrogen that were collected at the time of the mGFR procedure. Nonparametric Wilcoxon test, Spearman correlation, Bland-Altman analysis, bias (median difference), and accuracy (P15, P30) were used to compare mGFR with eGFR. For the entire study group, the mGFR was 77.9 ± 38.8 mL/min/1.73 m(2). Eight of the 14 estimating equations demonstrated values without a significant difference from the mGFR value and demonstrated a lower bias in Bland-Altman analysis. Three of these 8 equations based on a combination of creatinine and cystatin C (Schwartz et al. New equations to estimate GFR in children with CKD. J Am Soc Nephrol 2009;20:629-37; Schwartz et al. Improved equations estimating GFR in children with chronic kidney disease using an immunonephelometric determination of cystatin C. Kidney Int 2012;82:445-53; Chehade et al. New combined serum creatinine and cystatin C quadratic formula for GFR assessment in children. Clin J Am Soc Nephrol 2014;9:54-63) had the highest accuracy with approximately 60% of P15 and 80% of P30. In 10 patients with a single kidney, 7 with kidney transplant, and 11 additional children with short stature, values of the 3 equations had low bias and no significant difference when compared with mGFR. In conclusion, the 3 equations that used cystatin C, creatinine, and growth parameters performed in a superior manner over univariate equations based on either creatinine or cystatin C and also had good applicability in specific pediatric patients with single kidneys, those with a kidney transplant, and short stature. Thus, we suggest that eGFR calculations in pediatric clinical practice

  10. Glomerular filtration rate by 51chomium and 113mindium labeled EDTA in horses

    International Nuclear Information System (INIS)

    Maliska, C.; D'Almeida, J.; Pellegrini, P.M.; Schimit, T.S.; Pinho, W.R.; Lima, J.E.T.

    2009-01-01

    The glomerular filtration rate was determined in nine healthy horses, six male and three female, aged two to 12-year-old, by means of 51 Cr and 113m In labeled EDTA single injection technique. The glomerular filtration rate was calculated from the plasma disappearance curve and the volume of distribution of the radiotracer, 51 Cr-EDTA or 113m In-EDTA. The result (mean +- standard deviation) was 148.80 +- 26.42 m L.min -1 .100 kg. It is concluded that the measurement of glomerular filtration rate by 51 Cr-EDTA or 113m In-EDTA by single injection technique eliminates the bladder catheterization, and for its simplicity, convenience, accuracy, and low dose of radiation, can be used in horses as a method of choice in clinical routine. (author)

  11. Vibroacustic microvibrations enhance kidney blood supply, glomerular filtration and glutathione peroxidase activity in spontaneously hypertensive rats.

    Science.gov (United States)

    Miloradović, Zoran; Mihailović-Stanojević, Nevena; Jovović, Đurđica; Ivanov, Milan; Vajić, Una J; Karanović, Danijela; Grujić Milanović, Jelica

    2015-01-01

    Limited numbers of studies include research of microvibration therapy in experimental models. We examined effects of chronic vibroacustic-microvibration treatment on haemodynamics and anti-oxidative defense in experimental hypertension. Study was performed on chronically treated hypertensive and normotensive Wistar rats. Mean arterial pressure (MAP), cardiac output (CO), renal blood flow (RBF), glomerular filtration and activity of anti-oxidative enzymes were determined after three weeks treatment. Vibroacustic treatment had no influence on MAP and CO, but RBF was increased in both groups of treated rats. Additionally, vibroacustic treatment enhanced diuresis and increased glomerular filtration in hypertensive rats. Glutathione peroxidase (GSH-Px) activity was elevated in both treated rat strains, but activity of superoxide dismutase was unchanged. We conclude that microvibration treatment doesn't ameliorate hypertension but improves renal blood supply (trough diminished renal vascular resistance), glomerular filtration, diuresis, and enhances glutathione dependent anti-oxidant defense with more important beneficials in hypertensive animals.

  12. Glomerular filtration rate: estimation from fractional renal accumulation of 99mTc-DTPA (stannous)

    International Nuclear Information System (INIS)

    Gates, G.F.

    1982-01-01

    99mTc diethylenetriaminepentaacetic acid (stannous) is cleared from the blood by glomerular filtration. However, calculation of the glomerular filtration rate has required analysis of serial blood samples drawn over intervals of several hours in order to determine the radionuclide clearance rate. This lengthy procedure can be circumvented by the direct scintigraphic determination of fractional radionuclide accumulation within each kidney, occurring at a specified time interval after radionuclide administration. This value has been correlated with 24 hr creatinine clearance values in a group of hospitalized patients. From these data, a formula was derived allowing for estimation of total glomerular filtration rate, as well as individually for each kidney, without requiring blood samples. This procedure needs only 6 min of patient time

  13. Glomerular number and function are influenced by spontaneous and induced low birth weight in rats

    DEFF Research Database (Denmark)

    Schreuder, Michiel F; Nyengaard, Jens Randel; Fodor, M

    2005-01-01

    and experimental IUGR, induced by bilateral uterine artery ligation. Design-based stereologic methods were used. Urinary protein excretion was determined as a measure of renal damage. Results showed a decrease of approximately 20% in glomerular number in both groups of IUGR (control 35,400, naturally occurring...... IUGR 30,900, and experimental IUGR 28,000 glomeruli per kidney). Mean glomerular volume was increased in both IUGR groups, which was associated with an increased proteinuria. It is concluded that IUGR leads to a nephron endowment with a compensatory glomerular enlargement. This compensation...... is associated with more proteinuria in the long run. Uterine artery ligation in the pregnant rat is a suitable model to study the effects of IUGR on the kidney....

  14. Glomerular nerve endings in corial papillae of the pig lip skin.

    Science.gov (United States)

    Malinovský, L; Pác, L; Krivánková, L

    1982-01-01

    In the tops of corial papillae of the pig lip skin the authors sometimes observed besides typical sensory corpuscles also glomerular nerve endings. They are formed by one axon or they are polyaxon. The nerve fibres are richly branched in the formation. In electronogrammes a large number of axons is visible in cross sections round some of which there are more or less formed lamellous systems up to four lamellae. Between the axons there are nuclei of Schwann cells, on the surface there is a thin capsule of fibrocyte character. In non-primate mammals the typical receptor in the corium of the skin are simple corpuscles, in primates glomerular nerve endings. As concerns sensory corpuscles it is the other way round. The authors are of the opinion that the observed glomerular endings represent morphologically a transitory formation. With respect to the occurrence of lamellous complexes in the glomeruli, they can be considered as equivalent to simple sensory corpuscles with rapid adaptation.

  15. ABIN1 Determines Severity of Glomerulonephritis via Activation of Intrinsic Glomerular Inflammation.

    Science.gov (United States)

    Korte, Erik A; Caster, Dawn J; Barati, Michelle T; Tan, Min; Zheng, Shirong; Berthier, Celine C; Brosius, Frank C; Vieyra, Mark B; Sheehan, Ryan M; Kosiewicz, Michele; Wysoczynski, Marcin; Gaffney, Patrick M; Salant, David J; McLeish, Kenneth R; Powell, David W

    2017-12-01

    Transcription factor NF-κB regulates expression of numerous genes that control inflammation and is activated in glomerular cells in glomerulonephritis (GN). We previously identified genetic variants for a NF-κB regulatory, ubiquitin-binding protein ABIN1 as risk factors for GN in systemic autoimmunity. The goal was to define glomerular inflammatory events controlled by ABIN1 function in GN. Nephrotoxic serum nephritis was induced in wild-type (WT) and ubiquitin-binding deficient ABIN1[D485N] mice, and renal pathophysiology and glomerular inflammatory phenotypes were assessed. Proteinuria was also measured in ABIN1[D485N] mice transplanted with WT mouse bone marrow. Inflammatory activation of ABIN1[D472N] (D485N homolog) cultured human-derived podocytes, and interaction with primary human neutrophils were also assessed. Disruption of ABIN1 function exacerbated proteinuria, podocyte injury, glomerular NF-κB activity, glomerular expression of inflammatory mediators, and glomerular recruitment and retention of neutrophils in antibody-mediated nephritis. Transplantation of WT bone marrow did not prevent the increased proteinuria in ABIN1[D845N] mice. Tumor necrosis factor-stimulated enhanced expression and secretion of NF-κB-targeted proinflammatory mediators in ABIN1[D472N] cultured podocytes compared with WT cells. Supernatants from ABIN1[D472N] podocytes accelerated chemotaxis of human neutrophils, and ABIN1[D472N] podocytes displayed a greater susceptibility to injurious morphologic findings induced by neutrophil granule contents. These studies define a novel role for ABIN1 dysfunction and NF-κB in mediating GN through proinflammatory activation of podocytes. Copyright © 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  16. Defining Glomerular Disease in Mechanistic Terms: Implementing an Integrative Biology Approach in Nephrology.

    Science.gov (United States)

    Mariani, Laura H; Pendergraft, William F; Kretzler, Matthias

    2016-11-07

    Advances in biomedical research allow for the capture of an unprecedented level of genetic, molecular, and clinical information from large patient cohorts, where the quest for precision medicine can be pursued. An overarching goal of precision medicine is to integrate the large-scale genetic and molecular data with deep phenotypic information to identify a new mechanistic disease classification. This classification can ideally be used to meet the clinical goal of the right medication for the right patient at the right time. Glomerular disease presents a formidable challenge for precision medicine. Patients present with similar signs and symptoms, which cross the current disease categories. The diseases are grouped by shared histopathologic features, but individual patients have dramatic variability in presentation, progression, and response to therapy, reflecting the underlying biologic heterogeneity within each glomerular disease category. Despite the clinical challenge, glomerular disease has several unique advantages to building multilayered datasets connecting genetic, molecular, and structural information needed to address the goals of precision medicine in this population. Kidney biopsy tissue, obtained during routine clinical care, provides a direct window into the molecular mechanisms active in the affected organ. In addition, urine is a biofluid ideally suited for repeated measurement from the diseased organ as a liquid biopsy with potential to reflect the dynamic state of renal tissue. In our review, current approaches for large-scale data generation and integration along the genotype-phenotype continuum in glomerular disease will be summarized. Several successful examples of this integrative biology approach within glomerular disease will be highlighted along with an outlook on how achieving a mechanistic disease classification could help to shape glomerular disease research and care in the future. Copyright © 2016 by the American Society of Nephrology.

  17. Perfil das doenças glomerulares em um hospital público do Distrito Federal Profile of glomerular diseases in a public hospital of Federal District, Brazil

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    Fabio Humberto Ribeiro Paes Ferraz

    2010-09-01

    Full Text Available INTRODUÇÃO: As doenças glomerulares são uma causa frequente de doença renal crônica, sobretudo nos países em desenvolvimento. OBJETIVO: O objetivo deste estudo foi determinar o perfil destas glomerulopatias em um hospital público da cidade de Brasília, Distrito Federal. MÉTODOS: Foram realizadas 121 biopsias renais pela equipe de nefrologia do Hospital Regional da Asa Norte (HRAN entre agosto de 2005 e maio de 2009. Foram excluídas oito biopsias realizadas em pacientes transplantados renais e analisados os prontuários dos 113 pacientes restantes. Dados analisados: sexo, idade, exames laboratoriais, síndrome glomerular, diagnóstico clínico, grau de fibrose intersticial, uso de imunossupressores, necessidade de diálise e desfecho clínico. RESULTADOS: A média de idade foi 34,9 ± 16,2 anos, com predomínio masculino (51,3%. As principais síndromes glomerulares foram: síndrome nefrótica (41,6% e glomerulonefrite rapidamente progressiva (35,4%. Entre as glomerulopatias primárias, houve predomínio da glomeruloesclerose segmentar e focal (26,9% e da nefropatia por IgA (25% e entre as secundárias a nefrite lúpica (50% e a glomerulonefrite proliferativa exsudativa difusa (34,2%. A maioria dos pacientes fez uso de imunossupressores (68,1% e quase um terço deles (29,2% necessitou de diálise durante a internação. Evoluíram para terapia dialítica crônica 13,3% dos pacientes e 10,6% evoluíram a óbito. CONCLUSÃO: Este estudo poderá contribuir para melhor entendimento epidemiológico das doenças glomerulares no Distrito Federal, orientando na adoção de políticas públicas visando permitir rápido diagnóstico e manejo clínico das mesmas.INTRODUCTION: Glomerular diseases are a frequent etiology of chronic kidney disease, especially in the developing countries. OBJECTIVE: To determine the profile of such glomerulopathies in a public hospital located in the city of Brasilia, Federal District. METHODS: 121 renal biopsies in

  18. Correlation between glomerular filtration rate and urinary N acetyl-beta-D glucosaminidase in children with persistent proteinuria in chronic glomerular disease

    Directory of Open Access Journals (Sweden)

    Jeong Deok Hong

    2012-04-01

    Full Text Available Purpose: Urinary excretion of N acetyl-beta-D glucosaminidase (NAG and ?#11437;microglobulin (?#11437;M was increased in the presence of proximal tubular damage. Based on these urinary materials, we investigated the ability of expecting renal function in chronic glomerular diseases. In this study, we evaluated the relationship between glomerular filtration rate (GFR urinary NAG, and urinary ?#11437;M. Methods: We evaluated 52 children with chronic kidney disease at the Chung-Ang University Hospital between January 2003 and August 2009. We investigated the 24-hour urinalysis and hematologic values in all 52 patients. Serum creatinine, creatinine clearance (Ccr, serum cystatin C, urinary ?#11437;M and urinary NAG were measured. Results: Out of 52 patients, there were 13 children with minimal change in disease, 3 children with focal segmental glomerulosclerosis, 17 children with immunoglobulin A nephropathy, 15 children with Henoch-Schonlein purpua nephritis, 3 children with poststreptococcal glomerulonephritis, and 1 child with thin glomerular basement membrane disease. In these patients, there were significant correlation between the Ccr and urinary NAG (r=-0.817; P&lt;0.01, and between the GFR (as determined by Schwartz method and urinary NAG (r=- 0.821; P&lt;0.01. In addition, there was a significant correlation between the GFR (as determined by Bokencamp method and urinary NAG (r=- 0.858; P&lt;0.01. Conclusion: In our study, there was a significant correlation between the GFR and urinary NAG, but there was no correlation between the GFR and urinary ?#11437;M, suggesting that the GFR can be predicted by urinary NAG in patients with chronic glomerular disease.

  19. A microtechnique for radioisotopic determination of glomerular filtration rate in infants and children

    International Nuclear Information System (INIS)

    Braren, V.; Brill, A.B.; Touya, J.; Goddard, J.

    1982-01-01

    Our experience with a microtechnique using 99 mTc-DTPA for determination of glomerular filtraton rate in 172 children is presented. It is a simple finger-stick method carried out in a four-hour time period by trained nuclear medical personnel. The procedure meets all criteria for precise measurement of glomerular filtration rate, and the radiation dose is low. Proof of accuracy was obtained by comparison of this technique with concomitant 24-hour urinary creatinine clearance in a subset of children

  20. On determinants of glomerular filtration rate after inhibition of proximal tubular reabsorption

    DEFF Research Database (Denmark)

    Leyssac, P P; Karlsen, F M; Holstein-Rathlou, N H

    1994-01-01

    The carbonic anhydrase inhibitor acetazolamide (ACZ) inhibits the absolute rate of proximal reabsorption (APR), causes a reduction in glomerular filtration rate (GFR), and activates the tubuloglomerular feedback mechanism (TGF) resulting in afferent vasoconstriction. The quantitative importance...... of the afferent vasoconstriction for the reduced GFR was tested by addition of a vasodilator during continuous infusion of ACZ. Dopamine caused an increase in renal blood flow (RBF) to pre-ACZ levels. Glomerular capillary pressure (Pgc) and proximal tubular pressure (Pprox) increased in parallel (by 3.1 and 3...

  1. Measurement of glomerular filtration rate by impulse synthesis: Clinical validation and optimization

    International Nuclear Information System (INIS)

    Palagi, B.; Verga, P.; Broggi, A.; Picozzi, R.; Villa, F.; Guzzini, F.; Cozzi, C.; Tomasi, A.

    1988-01-01

    Impulse synthesis is a technique which relies upon the logic of continuous infusion but extracts the clearance value from single-injection data by shifting and adding them until an asymptotic value is attained. This study has been aimed at validating and optimizing clinically the measurement of glomerular filtration rate by impulse synthesis. A single intravenous injection of 51 Cr-EDTA has been made in 32 patients and plasma activity monitored over the next 6 h. Glomerular filtration rate computed by a single-exponential fit method (GFR-SEF) has been shown to be significantly (p [de

  2. Determination of glomerular filtration rate and renal plasma flow with radioisotopes

    International Nuclear Information System (INIS)

    Duarte, C.G.; Elveback, L.R.; Liedtke, J.R.

    1983-01-01

    The concept of glomerular filtration and the clearance of inulin and creatinine as an index of renal function, advantages in the use of radioisotopes to measure glomerular filtration rate, and the clearance of /sup 125/I-iothalamate in (1) standard clearance and (2) subcutaneous short-clearance studies. The concept of renal plasma flow and clearance of para-aminohippurate, the use of radioisotopes for the measurement of renal plasma flow, and the clearance of /sup 131/I-Hippuran (iodohippurate sodium). Laboratory procedures for standard renal clearances with labeled iothalamate and Hippuran are given in detail, as is the short iothalamate clearance procedure

  3. Transitory cell attachments in the differentiating glomerular epithelium of the opossum metanephros.

    Science.gov (United States)

    Krause, W J; Cutts, J H

    1980-01-01

    Numerous transitory intercellular attachments are observed between the central, lateral surfaces of adjacent glomerular epithelial cells in the differentiating renal corpuscle. The junctions are characterized by an increased electron density of the adjacent cell membranes and cytoplasm. The intervening intercellular space may contain an amorphous material of moderate electron density. The distribution and position of such temporary cell attachments, together with their modification and subsequent loss during the differentiation of podocytes, suggest that they play an important role in the histogenesis of the glomerular epithelium.

  4. A distributed solute model: an extended two-pore model with application to the glomerular sieving of Ficoll.

    Science.gov (United States)

    Öberg, Carl M; Groszek, Joseph J; Roy, Shuvo; Fissell, William H; Rippe, Bengt

    2017-04-19

    One of the many unresolved questions regarding the permeability of the glomerular filtration barrier is the reason behind the marked difference in permeability between albumin and polysaccharide probe molecules such as Ficoll and dextran of the same molecular size. Although the differences in permeability have been mainly attributed to charge effects, we have previously shown that this would require a highly charged filtration barrier, having a charge density that is ~10 times more than that on the albumin molecule. In this article, the classic two-pore model was extended by introducing size distributions on the solute molecules, making them conformationally flexible. Experimental sieving data for Ficoll from the rat glomerulus and from precision-made silicon nanopore membranes were analyzed using the model. For the rat glomerulus a small pore radius of 36.2 Å and a geometric standard deviation (gSD) for the Ficoll size-distribution of 1.16 was obtained. For the nanopore membranes, a gSD of 1.24 and a small-pore radius of 43 Å was found. Interestingly, a variation of only ~16% in the size of the polysaccharide molecule is sufficient to explain the difference in permeability between albumin and Ficoll. Also, in line with previous data, the effects of applying a size-distribution on the solute molecule are only evident when the molecular size is close to the pore size. Surely there is at least some variation in the pore radii and, likely, the gSD obtained in the current study is an overestimation of the "true" variation in the size of the Ficoll molecule.

  5. Methods for characterizing differences in longitudinal glomerular filtration rate changes between children with glomerular chronic kidney disease and those with nonglomerular chronic kidney disease.

    Science.gov (United States)

    Pierce, Christopher B; Cox, Christopher; Saland, Jeffrey M; Furth, Susan L; Muñoz, Alvaro

    2011-09-01

    The rate of decline of glomerular filtration rate (GFR) in children with chronic kidney disease (CKD) can vary, even among those with similar diagnoses. Classic regression methods applied to the log-transformed GFR (i.e., lognormal) quantify only rigid shifts in a given outcome. The generalized gamma distribution offers an alternative approach for characterizing the heterogeneity of effect of an exposure on a positive, continuous outcome. Using directly measured GFR longitudinally assessed between 2005 and 2010 in 529 children enrolled in the Chronic Kidney Disease in Children Study, the authors characterized the effect of glomerular CKD versus nonglomerular CKD diagnoses on the outcome, measured as the annualized GFR ratio. Relative percentiles were used to characterize the heterogeneity of effect of CKD diagnosis across the distribution of the outcome. The rigid shift assumed by the classic mixed models failed to capture the fact that the greatest difference between the glomerular and nonglomerular diagnosis' annualized GFR ratios was in children who exhibited the fastest GFR declines. Although this difference was enhanced in children with an initial GFR level of 45 mL/minute/1.73 m(2) or less, the effect of diagnosis on outcome was not significantly modified by level. Generalized gamma models captured heterogeneity of effect more richly and provided a better fit to the data than did conventional lognormal models.

  6. Neutrophil FcγRIIA promotes IgG-mediated glomerular neutrophil capture via Abl/Src kinases.

    Science.gov (United States)

    Nishi, Hiroshi; Furuhashi, Kazuhiro; Cullere, Xavier; Saggu, Gurpanna; Miller, Mark J; Chen, Yunfeng; Rosetti, Florencia; Hamilton, Samantha L; Yang, Lihua; Pittman, Spencer P; Liao, Jiexi; Herter, Jan M; Berry, Jeffrey C; DeAngelo, Daniel J; Zhu, Cheng; Tsokos, George C; Mayadas, Tanya N

    2017-10-02

    The kidney glomerular capillaries are frequent sites of immune complex deposition and subsequent neutrophil accumulation in post-infectious and rapidly progressive glomerulonephritis. However, the mechanisms of neutrophil recruitment remain enigmatic, and there is no targeted therapeutic to avert this proximal event in glomerular inflammation. The uniquely human activating Fc receptor FcγRIIA promotes glomerular neutrophil accumulation and damage in anti-glomerular basement membrane-induced (anti-GBM-induced) glomerulonephritis when expressed on murine neutrophils. Here, we found that neutrophils are directly captured by immobilized IgG antibodies under physiological flow conditions in vitro through FcγRIIA-dependent, Abl/Src tyrosine kinase-mediated F-actin polymerization. Biophysical measurements showed that the lifetime of FcγRIIA-IgG bonds increased under mechanical force in an F-actin-dependent manner, which could enable the capture of neutrophils under physiological flow. Kidney intravital microscopy revealed that circulating neutrophils, which were similar in diameter to glomerular capillaries, abruptly arrested following anti-GBM antibody deposition via neutrophil FcγRIIA and Abl/Src kinases. Accordingly, inhibition of Abl/Src with bosutinib reduced FcγRIIA-mediated glomerular neutrophil accumulation and renal injury in experimental, crescentic anti-GBM nephritis. These data identify a pathway of neutrophil recruitment within glomerular capillaries following IgG deposition that may be targeted by bosutinib to avert glomerular injury.

  7. Tubular and glomerular proteinuria in HIV-infected adults with estimated glomerular filtration rate ≥ 60 ml/min per 1.73 m2.

    Science.gov (United States)

    Reynes, Jacques; Cournil, Amandine; Peyriere, Hélène; Psomas, Christina; Guiller, Elsa; Chatron, Marlène; Cristol, Jean-Paul; Badiou, Stéphanie

    2013-05-15

    To assess the frequency of glomerular and tubular proteinuria in a cohort of HIV-infected patients, and to determine the factors associated with each type of injury. Cross-sectional study of 1210 consecutive HIV-infected adults followed in HIV outpatient unit (Montpellier/France). Spot urine protein to creatinine (uPCR), albumin to creatinine (uACR) and albumin to protein (uAPR) ratios were assessed. Glomerular injury was defined as uACR at least 30 mg/g or uPCR at least 200 mg/g with uAPR at least 0.4. Tubular injury was defined as uPCR 200 mg/g or more with uAPR less than 0.4. Multivariate logistic regression identified independent factors of each type of proteinuria, in the 1158 patients with estimated glomerular filtration rate (eGFR) at least 60 ml/min per 1.73 m, using re-expressed modification of diet in renal disease equation. Frequency of proteinuria was 18.2% among patients with eGFR at least 60 ml/min per 1.73 m consisting in tubular proteinuria for 50.7% of them. Factors associated with glomerular proteinuria were age [OR 1.34/10-year increment (95%CI: 1.08-1.66)], diabetes [OR 3.37 (95%CI: 1.53-7.44)], and arterial hypertension [OR 2.52 (95%CI: 1.36-4.66)]. Factors associated with tubular proteinuria were age [OR 1.43 (95%CI: 1.14-1.79)], current tenofovir use [OR 3.52 (95%CI: 1.86-6.65)], hepatitis C co-infection [OR 1.62 (95%CI: 1.00-2.65)], AIDS stage [OR 1.83 (95%CI: 1.18-2.82)], CD4 cell count less than 200 per μl [OR 2.48 (95%CI: 1.31-4.70)]. This study distinguished risk factors for tubular injury, mainly related to HIV disease and its treatment (tenofovir), and glomerular injury, linked to non HIV-related variables (age, diabetes, hypertension). Measuring uPCR, uACR and uAPR may help with the detection and specific management of early chronic kidney disease in HIV-infected patients having normal or sub-normal eGFR.

  8. Glomerular changes in trisomy 18-related horseshoe kidney: report of a case and review of the literature

    Directory of Open Access Journals (Sweden)

    Giuseppina Parodo

    2012-10-01

    Full Text Available A case of horseshoe kidney is reported in a 11 week-old fetus affected by trisomy 18. Macroscopic examination did not show any other pathological change. The histological picture of the fused-kidney was characterized by architectural and glomerular changes. At x 100 magnification, large areas of metanephric mesenchyme, characterized by spindle cells surrounded by a loose oedematous stroma, were detected in the deep cortex and in the medulla. At higher power, multiple glomerular changes were observed. Maldeveloped glomeruli showed enlarged capsular spaces, adhesions between vascular tuft and capsular cells, podocytes in multiple layers, and large glomerular bodies formed by two vascular tufts. Our data confirm previous reports on glomerular changes in horseshoe kidney, and reinforce the hypothesis that horseshoe kidney should not be considered a simple fusion problem, but a complex developmental abnormality, possibly involving glomerular development.

  9. Antibody response against the glomerular basement membrane protein agrin in patients with transplant glomerulopathy.

    NARCIS (Netherlands)

    Joosten, S.A.; Sijpkens, Y.W.; Ham, V. van; Trouw, L.A.; Vlag, J. van der; Heuvel, L.P.W.J. van den; Kooten, C. van; Paul, L.C.

    2005-01-01

    Chronic allograft nephropathy (CAN) of renal allografts is still the most important cause of graft loss. A subset of these patients have transplant glomerulopathy (TGP), characterized by glomerular basement membrane (GBM) duplications, but of unknown etiology. Recently, a role for the immune system

  10. Expression of Toll-Like Receptor 4 in Glomerular Endothelial Cells under Diabetic Conditions

    International Nuclear Information System (INIS)

    Takata, Shunsuke; Sawa, Yoshihiko; Uchiyama, Takanobu; Ishikawa, Hiroyuki

    2013-01-01

    Diabetic conditions promote glomerulosclerosis by mesangial cells but the mechanisms are not fully elucidated. The present study evaluated the expression of toll-like receptor 4 in glomerular endothelial cells in the streptozotocin (STZ)-induced type 1 diabetic mouse (ICR-STZ) and the type 2 diabetic KK/TaJcl mouse which were fed a high fat diet feed (KK/Ta-HF). In the ICR-STZ and KK/Ta-HF almost glomeruli were immunostained with anti-TLR4 but there was no glomerulus immunostained by ani-TLR4 in the control ICR and KK/Ta. Laser-scanning confocal microscopy showed that the TLR4-positive region did not coincide with the podoplanin-positive region but coincide with the PECAM-1- and VE-cadherin-positive regions in the glomeruli of the ICR-STZ and KK/Ta-HF. The in situ hybridization showed that almost signals for TLR4 mRNA were present in the glomerulus of the ICR-STZ and KK/Ta-HF to a stronger extent than in the control ICR and KK/Ta. These suggest that glomerular endothelial cells usually express the TLR4 gene and hyperglycemia in the diabetic condition induces the TLR4 protein expression in the glomerular capillary endothelial cells. Cytokine productions through the TLR signaling pathway in glomerular endothelial cells may allow mesangial cells to produce extracellular matrix proteins in the diabetic milieu

  11. Influencing factors of Gate's method to measure of glomerular filtration rate

    International Nuclear Information System (INIS)

    Wu Ha; Shi Hongcheng

    2009-01-01

    Glomerular filtration rate (GFR) is an important criterion to estimate renal function. 99 Tc m - diethylenetrimainepentaacetic acid renal dynamic imaging is one of method to measure GFR that it have the characteristics of simple and accurate. But the Gate's method may be influenced by many factors such as dose of imaging agent, outlined of regions of interest, kidney depth, and so on. (authors)

  12. Measurement of glomerular filtration rate in adults: accuracy of five single-sample plasma clearance methods

    DEFF Research Database (Denmark)

    Rehling, M; Rabøl, A

    1989-01-01

    After an intravenous injection of a tracer that is removed from the body solely by filtration in the kidneys, the glomerular filtration rate (GFR) can be determined from its plasma clearance. The method requires a great number of blood samples but collection of urine is not needed. In the present...

  13. Reliability of estimated glomerular filtration rate in patients treated with platinum containing therapy

    DEFF Research Database (Denmark)

    Lauritsen, Jakob; Gundgaard, Maria G; Mortensen, Mette S

    2014-01-01

    Estimates of glomerular filtration rate (eGFR) are widely used when administering nephrotoxic chemotherapy. No studies performed in oncology patients have shown whether eGFR can safely substitute a measured GFR (mGFR) based on a marker method. We aimed to assess the validity of four major formulas...

  14. A urinary proteome-based classifier for the early detection of decline in glomerular filtration

    DEFF Research Database (Denmark)

    Pontillo, Claudia; Jacobs, Lotte; Staessen, Jan A

    2017-01-01

    BACKGROUND: Chronic kidney disease (CKD) progression is currently assessed by a decline in estimated glomerular filtration rate (eGFR) and/or an increase in urinary albumin excretion (UAE). However, these markers are considered either to be late-stage markers or to have low sensitivity...

  15. Impaired autoregulation of the glomerular filtration rate in patients with nondiabetic nephropathies

    DEFF Research Database (Denmark)

    Christensen, P K; Hommel, E E; Clausen, P

    1999-01-01

    BACKGROUND: The ability of the kidney to maintain constancy of the glomerular filtration rate (GFR) over a wide range of renal perfusion pressures is termed autoregulation. Defective autoregulation of GFR has been demonstrated in diabetic nephropathy. Whether this is also the case in patients...

  16. Stable glomerular filtration rate in normotensive IDDM patients with stable microalbuminuria. A 5-year prospective study

    DEFF Research Database (Denmark)

    Mathiesen, E R; Feldt-Rasmussen, B; Hommel, E

    1997-01-01

    OBJECTIVE: To investigate the long-term course of glomerular filtration rate (GFR) in IDDM patients with microalbuminuria in order to identify patients with stable or declining kidney function over a 5-year study. RESEARCH DESIGN AND METHODS: Forty normotensive (129 +/- 11/80 +/- 8 mmHg) IDDM...

  17. Rapid decline in glomerular filtration rate during the first weeks following heart transplantation

    DEFF Research Database (Denmark)

    Hornum, M; Andersen, Mads Jønsson; Gustafsson, F

    2011-01-01

    We hypothesized that a decrease in renal function is seen immediately after heart transplantation (HTX) with little recovery over time. Twelve consecutive patients had their glomerular filtration rate (GFR) measured using (51)Cr-ethylenediaminetetraacetic acid (EDTA) measured GFR (mGFR) before...

  18. A re-evaluation of the determinants of glomerular filtration rate

    DEFF Research Database (Denmark)

    Karlsen, F M; Holstein-Rathlou, N H; Leyssac, P P

    1995-01-01

    Several factors are potentially able to change the glomerular filtration rate (GFR) and thereby participate in its regulation, but only a few factors seem to be physiologically important. The variable nature of proximal tubular pressure should be recognized as important in the regulation of GFR...

  19. Evaluation of glomerular function in individual kidneys using dynamic magnetic resonance imaging

    International Nuclear Information System (INIS)

    Fukuda, Y.; Watanabe, H.; Tomita, T.; Katayama, H.; Miyano, T.; Yabuta, K.

    1996-01-01

    We used the fast field-echo technique of magnetic resonance (MR) imaging with an intravenous bolus injection of paramagnetic contrast agent to evaluate glomerular function. The time-dependent curves of changes in signal intensity observed in the renal cortex and renal medulla brought about by the paramagnetic contrast agent allowed insight into excretory kinetics. The time at which the cortical and medullary curves cross, the cortico-medullary (C-M) junction time, was delayed with a decrease in glomerular function. The mean C-M junction time in both kidneys showed a significant inverse correlation with total creatinine clearance (Ccr), indicating the glomerular filtration rate. The C-M junction time in an individual kidney also showed an inverse correlation with individual Ccr in each kidney. Results suggest that dynamic MR imaging is a useful tool in evaluating renal morphology and in evaluating semiquantitatively the glomerular function of the kidneys, singly and together, in a manner analogous to radionuclide scintigraphy. (orig.). With 6 figs

  20. Glomerular and tubular damage markers are elevated in patients with diabetes

    NARCIS (Netherlands)

    Nauta, Ferdau L.; Boertien, Wendy E.; Bakker, Stephan J. L.; van Goor, Harry; van Oeveren, Wim; de Jong, Paul E.; Bilo, Henk; Gansevoort, Ron T.

    OBJECTIVE: We investigated in a cross-sectional study the levels of serum and urinary damage markers in diabetic patients (n = 94) and nondiabetic control subjects (n = 45) to study the association of glomerular (IgG), proximal tubular (kidney injury molecule [KIM]-1, N-acetyl-β-d-glucosaminidase

  1. Early B-cell factor 1 is an essential transcription factor for postnatal glomerular maturation.

    Science.gov (United States)

    Fretz, Jackie A; Nelson, Tracy; Velazquez, Heino; Xi, Yougen; Moeckel, Gilbert W; Horowitz, Mark C

    2014-05-01

    The coordination of multiple cytokines and transcription factors with their downstream signaling pathways has been shown to be integral to nephron maturation. Here we present a completely novel role for the helix-loop-helix transcription factor Early B-cell factor 1 (Ebf1), originally identified for B-cell maturation, for the proper maturation of glomerular cells from mesenchymal progenitors. The expression of Ebf1 was both spatially and temporally regulated within the developing cortex and glomeruli. Using Ebf1-null mice, we then identified biochemical, metabolic, and histological abnormalities in renal development that arose in the absence of this transcription factor. In the Ebf1 knockout mice, the developed kidneys show thinned cortices and reduced glomerular maturation. The glomeruli showed abnormal vascularization and severely effaced podocytes. The mice exhibited early albuminuria and elevated blood urea nitrogen levels. Moreover, the glomerular filtration rate was reduced >66% and the expression of podocyte-derived vascular endothelial growth factor A was decreased compared with wild-type control mice. Thus, Ebf1 has a significant and novel role in glomerular development, podocyte maturation, and the maintenance of kidney integrity and function.

  2. Measuring rat kidney glomerular number and size in vivo with MRI.

    Science.gov (United States)

    Baldelomar, Edwin J; Charlton, Jennifer R; Beeman, Scott C; Bennett, Kevin M

    2018-03-01

    number is highly variable in humans and is thought to play an important role in renal health. Chronic kidney disease (CKD) is the result of too few nephrons to maintain homeostasis. Currently, nephron number can only be determined invasively or as a terminal assessment. Due to a lack of tools to measure and track nephron number in the living, the early stages of CKD often go unrecognized, preventing early intervention that might halt the progression of CKD. In this work, we present a technique to directly measure glomerular number ( N glom ) and volume in vivo in the rat kidney ( n = 8) using MRI enhanced with the novel contrast agent cationized ferritin (CFE-MRI). Adult male rats were administered intravenous cationized ferritin (CF) and imaged in vivo with MRI. Glomerular number was measured and each glomerulus was spatially mapped in 3D in the image. Mean apparent glomerular volume (a V glom ) and intrarenal distribution of the individual glomerular volume (IGV), were also measured. These metrics were compared between images of the same kidneys scanned in vivo and ex vivo with CFE-MRI. In vivo N glom and a V glom correlated to ex vivo metrics within the same kidneys and were within 10% of N glom and a V glom previously validated by stereologic methods. This is the first report of direct in vivo measurements of N glom and a V glom , introducing an opportunity to investigate mechanisms of renal disease progression and therapeutic response over time.

  3. estimated glomerular filtration rate and risk of survival in acute stroke

    African Journals Online (AJOL)

    2014-03-03

    Mar 3, 2014 ... the risk of survival in acute stroke. INTRODUCTION. Stroke is independently associated with impairment in the structure and function of the glomerulus. (1). Estimated Glomerular Filtration Rate (GFR) as determined by the four-item Modification of diet in renal disease (MDRD) equation is a fairly reliable.

  4. Comparative evaluation of quantitative glomerular filtration rate measured by isotopic and nonisotopic methods

    International Nuclear Information System (INIS)

    Balachandran, S.; Toguri, A.G.; Petrusick, T.W.; Abbott, L.C.

    1981-01-01

    Good correlation of glomerular filtration rate (GFR) measured isotopically from plasma disappearance of Tc-99m-DTPA (Sn) was shown with inulin clearance, creatinine clearance, and graded radionuclide imaging. The isotopic GFR is a simple, urineless technique not requiring continuous infusion that enables one to perform simultaneous renal imaging with one radiotracer

  5. Glomerular filtration rate estimation: performance of serum cystatin C-based prediction equations.

    Science.gov (United States)

    Weinert, Letícia Schwerz; Camargo, Eduardo Guimarães; Soares, Ariana A; Silveiro, Sandra Pinho

    2011-11-01

    Serum creatinine measurement is a mainstay in the routine laboratory evaluation of renal function, despite of having several disadvantages. Cystatin C, on the other hand, suffers less influence of gender and muscle mass and has been proposed as a more sensitive marker for glomerular filtration rate. However, serum endogenous markers should not be used alone to assess glomerular filtration rate. Creatinine-based equations such as the modification of diet in renal disease (MDRD) and Cockcroft-Gault are widely used despite their limitations. A large number of cystatin C-based prediction equations were developed in recent years, in diverse populations, with different laboratory assays and methods. Several studies demonstrated that cystatin C-based equations are reliable markers of glomerular filtration rate and can be used for diagnosis, evaluation and follow-up of kidney disease. They are simpler than creatinine-based equations and have at least the same accuracy and precision for glomerular filtration rate estimation. In conclusion, diabetes mellitus, cystic fibrosis, kidney transplantation, HIV-infection, and cirrhosis are clinical situations where cystatin C-based equations can be useful. Extremes of age such as childhood and advanced age have also been evaluated with favorable results.

  6. Reduced glomerular angiotensin II receptor density in diabetes mellitus in the rat: time course and mechanism

    International Nuclear Information System (INIS)

    Wilkes, B.M.

    1987-01-01

    Glomerular angiotensin II receptors are reduced in number in early diabetes mellitus, which may contribute to hyperfiltration and glomerular injury. The time course and role of the renin-angiotensin-aldosterone system in the pathogenesis of the receptor abnormality were studied in male Sprague-Dawley rats made diabetic with streptozotocin (65 mg, iv). Glomerular angiotensin II receptors were measured by Scatchard analysis; insulin, renin activity, angiotensin II, and aldosterone were measured by RIA. Diabetes mellitus was documented at 24 h by a rise in plasma glucose (vehicle-injected control, 133 +/- 4; diabetic, 482 +/- 22 mg/dl and a fall in plasma insulin (control, 53.1 +/- 5.7; diabetic, 35.6 +/- 4.0 microIU/ml. At 24 h glomerular angiotensin II receptor density was decreased by 26.5% in diabetic rats (control, 75.5 +/- 9.6 X 10(6); diabetic, 55.5 +/- 8.3 X 10(6) receptors/glomerulus. Receptor occupancy could not explain the defect, because there was reduced binding in diabetic glomeruli after pretreatment with 3 M MgCl 2 , a maneuver that caused dissociation of previously bound hormone. There was a progressive return of the receptor density toward normal over the 60 days following induction of diabetes, with diabetic glomeruli measuring 22.7%, 14.8%, and 3.7% fewer receptors than age-matched controls at 11 days, 1 month, and 2 months, respectively

  7. REPRODUCTIVE CONDITION, GLOMERULAR ADENOSINE DIPHOSPHATASE ACTIVITY, AND PLATELET-AGGREGATION IN THE RAT - EFFECT OF ENDOTOXIN

    NARCIS (Netherlands)

    VISSCHER, CA; FAAS, MM; BAKKER, WW; SCHUILING, GA

    1993-01-01

    In experiment A, the activity of the glomerular antithrombotic enzyme adenosine diphosphatase (ADPase) and the sensitivity of this enzyme for endotoxin (1.0 mug/kg BW) in various reproductive conditions of female rats were studied through use of enzyme histochemical methods. In experiment B, the

  8. A urinary proteome-based classifier for the early detection of decline in glomerular filtration

    NARCIS (Netherlands)

    Pontillo, Claudia; Jacobs, Lotte; Staessen, Jan A.; Schanstra, Joost P.; Rossing, Peter; Heerspink, Hiddo J. L.; Siwy, Justyna; Mullen, William; Vlahou, Antonia; Mischak, Harald; Vanholder, Ray; Zuerbig, Petra; Jankowski, Joachim

    2016-01-01

    BACKGROUND: Chronic kidney disease (CKD) progression is currently assessed by a decline in estimated glomerular filtration rate (eGFR) and/or an increase in urinary albumin excretion (UAE). However, these markers are considered either to be late-stage markers or to have low sensitivity or

  9. QUANTIFICATION OF GLOMERULAR EPITHELIAL-CELL ADHESION BY USING ANTI-DNA ANTIBODIES IN ELISA

    NARCIS (Netherlands)

    COERS, W; SMEENK, RJT; SALANT, DJ; WEENING, JJ

    A sensitive and reproducible microassay is described for quantification of adhesion of cells to matrix-coated 96-wells plates under different experimental conditions. For this purpose glomerular visceral epithelial cells (GVEC) were used. Attached GVEC were fixed with methanol and incubated with a

  10. Glomerular disease search filters for Pubmed, Ovid Medline, and Embase: a development and validation study.

    Science.gov (United States)

    Hildebrand, Ainslie M; Iansavichus, Arthur V; Lee, Christopher W C; Haynes, R Brian; Wilczynski, Nancy L; McKibbon, K Ann; Hladunewich, Michelle A; Clark, William F; Cattran, Daniel C; Garg, Amit X

    2012-06-06

    Tools to enhance physician searches of Medline and other bibliographic databases have potential to improve the application of new knowledge in patient care. This is particularly true for articles about glomerular disease, which are published across multiple disciplines and are often difficult to track down. Our objective was to develop and test search filters for PubMed, Ovid Medline, and Embase that allow physicians to search within a subset of the database to retrieve articles relevant to glomerular disease. We used a diagnostic test assessment framework with development and validation phases. We read a total of 22,992 full text articles for relevance and assigned them to the development or validation set to define the reference standard. We then used combinations of search terms to develop 997,298 unique glomerular disease filters. Outcome measures for each filter included sensitivity, specificity, precision, and accuracy. We selected optimal sensitive and specific search filters for each database and applied them to the validation set to test performance. High performance filters achieved at least 93.8% sensitivity and specificity in the development set. Filters optimized for sensitivity reached at least 96.7% sensitivity and filters optimized for specificity reached at least 98.4% specificity. Performance of these filters was consistent in the validation set and similar among all three databases. PubMed, Ovid Medline, and Embase can be filtered for articles relevant to glomerular disease in a reliable manner. These filters can now be used to facilitate physician searching.

  11. MRI-based glomerular morphology and pathology in whole human kidneys

    Science.gov (United States)

    Beeman, Scott C.; Cullen-McEwen, Luise A.; Puelles, Victor G.; Zhang, Min; Wu, Teresa; Baldelomar, Edwin J.; Dowling, John; Charlton, Jennifer R.; Forbes, Michael S.; Ng, Amanda; Wu, Qi-zhu; Armitage, James A.; Egan, Gary F.; Bertram, John F.

    2014-01-01

    Nephron number (Nglom) and size (Vglom) are correlated with risk for chronic cardiovascular and kidney disease and may be predictive of renal allograft viability. Unfortunately, there are no techniques to assess Nglom and Vglom in intact kidneys. This work demonstrates the use of cationized ferritin (CF) as a magnetic resonance imaging (MRI) contrast agent to measure Nglom and Vglom in viable human kidneys donated to science. The kidneys were obtained from patients with varying levels of cardiovascular and renal disease. CF was intravenously injected into three viable human kidneys. A fourth control kidney was perfused with saline. After fixation, immunofluorescence and electron microscopy confirmed binding of CF to the glomerulus. The intact kidneys were imaged with three-dimensional MRI and CF-labeled glomeruli appeared as punctate spots. Custom software identified, counted, and measured the apparent volumes of CF-labeled glomeruli, with an ∼6% false positive rate. These measurements were comparable to stereological estimates. The MRI-based technique yielded a novel whole kidney distribution of glomerular volumes. Histopathology demonstrated that the distribution of CF-labeled glomeruli may be predictive of glomerular and vascular disease. Variations in CF distribution were quantified using image texture analyses, which be a useful marker of glomerular sclerosis. This is the first report of direct measurement of glomerular number and volume in intact human kidneys. PMID:24647716

  12. Urinary excretion of neutral proteinases in nephrotic rats with a glomerular disease

    NARCIS (Netherlands)

    Davin, J. C.; Davies, M.; Foidart, J. M.; Foidart, J. B.; Dechenne, C. A.; Mahieu, P. R.

    1987-01-01

    A proliferative glomerulonephritis was induced in rats pre-immunized with rabbit IgG by injecting intravenously a sub-nephrotoxic dose of rabbit anti-glomerular basement membrane (GBM) IgG (A rats). Most rats (80%) developed a severe proteinuria (greater than 100 mg/24 hr) within two to five days

  13. Mutations in Complement Factor H Impair Alternative Pathway Regulation on Mouse Glomerular Endothelial Cells in Vitro

    NARCIS (Netherlands)

    Loeven, M.A.; Rops, A.; Lehtinen, M.J.; Kuppevelt, T.H. van; Daha, M.R.; Smith, R.J.; Bakker, M.A.H.; Berden, J.H.; Rabelink, T.J.; Jokiranta, T.S.; Vlag, J. van der

    2016-01-01

    Complement factor H (FH) inhibits complement activation and interacts with glomerular endothelium via its complement control protein domains 19 and 20, which also recognize heparan sulfate (HS). Abnormalities in FH are associated with the renal diseases atypical hemolytic uremic syndrome and dense

  14. Structural Alterations of the Glomerular Wall And Vessels in Early Stages of Diabetes Mellitus: Light and Transmission Electron Microscopic Study

    Directory of Open Access Journals (Sweden)

    Dkhil MA

    2007-01-01

    Full Text Available Objective: The capillary changes at the initial stage of diabetes may show an angioarchitecture clearly different from those of later stages and,/or very severe glomerular change. However, the onset of alterations in the early phases is unclear. This study attempts to determine the functional and structural alterations of the glomerular wall and vesicles in the early stage of diabetes.Material and Methods: Twenty-five adult rats were used in this study. They were divided into two groups: the first group of five was used as a control .The second group of 20 (the experimental group was injected intraperitoneally by a single dose of streptozotocin to induce hyperglycemia. Rats were sacrificed after ten days, two months, and four months.Five rats at two months of age with hyperglycemia were treated with insulin for eight weeks. Renal tissues were prepared by routine technique for light and transmission electron microscopic evaluation. Results: By light microscopy after ten days of induced hyperglycemia, there were no structural modifications detected either in renal glomerular fine vessels or in the glomerular basement membrane of the glomerular capillaries. After two months, there was a moderate glomerular enlargement and dilatation of glomerular capillaries, afferent, and efferent arterioles. After four months, glomerular basement membrane thickening was the only structural alteration observed. Recovery of the glomerular alterations was observed after two months of treatment with insulin. Conclusion: In early stages of diabetes mellitus in rats, there was an increase in the diameter of glomerular vessels. In later stages of the disease, the reverse was seen, but insulin treatment had a positive role in reversing these changes in the study subjects.

  15. The Prediction of Key Cytoskeleton Components Involved in Glomerular Diseases Based on a Protein-Protein Interaction Network

    Science.gov (United States)

    Ju, Wenjun; Li, Xuejuan; Li, Shao; Ding, Jie

    2016-01-01

    Maintenance of the physiological morphologies of different types of cells and tissues is essential for the normal functioning of each system in the human body. Dynamic variations in cell and tissue morphologies depend on accurate adjustments of the cytoskeletal system. The cytoskeletal system in the glomerulus plays a key role in the normal process of kidney filtration. To enhance the understanding of the possible roles of the cytoskeleton in glomerular diseases, we constructed the Glomerular Cytoskeleton Network (GCNet), which shows the protein-protein interaction network in the glomerulus, and identified several possible key cytoskeletal components involved in glomerular diseases. In this study, genes/proteins annotated to the cytoskeleton were detected by Gene Ontology analysis, and glomerulus-enriched genes were selected from nine available glomerular expression datasets. Then, the GCNet was generated by combining these two sets of information. To predict the possible key cytoskeleton components in glomerular diseases, we then examined the common regulation of the genes in GCNet in the context of five glomerular diseases based on their transcriptomic data. As a result, twenty-one cytoskeleton components as potential candidate were highlighted for consistently down- or up-regulating in all five glomerular diseases. And then, these candidates were examined in relation to existing known glomerular diseases and genes to determine their possible functions and interactions. In addition, the mRNA levels of these candidates were also validated in a puromycin aminonucleoside(PAN) induced rat nephropathy model and were also matched with existing Diabetic Nephropathy (DN) transcriptomic data. As a result, there are 15 of 21 candidates in PAN induced nephropathy model were consistent with our predication and also 12 of 21 candidates were matched with differentially expressed genes in the DN transcriptomic data. By providing a novel interaction network and prediction, GCNet

  16. The Prediction of Key Cytoskeleton Components Involved in Glomerular Diseases Based on a Protein-Protein Interaction Network.

    Science.gov (United States)

    Ding, Fangrui; Tan, Aidi; Ju, Wenjun; Li, Xuejuan; Li, Shao; Ding, Jie

    2016-01-01

    Maintenance of the physiological morphologies of different types of cells and tissues is essential for the normal functioning of each system in the human body. Dynamic variations in cell and tissue morphologies depend on accurate adjustments of the cytoskeletal system. The cytoskeletal system in the glomerulus plays a key role in the normal process of kidney filtration. To enhance the understanding of the possible roles of the cytoskeleton in glomerular diseases, we constructed the Glomerular Cytoskeleton Network (GCNet), which shows the protein-protein interaction network in the glomerulus, and identified several possible key cytoskeletal components involved in glomerular diseases. In this study, genes/proteins annotated to the cytoskeleton were detected by Gene Ontology analysis, and glomerulus-enriched genes were selected from nine available glomerular expression datasets. Then, the GCNet was generated by combining these two sets of information. To predict the possible key cytoskeleton components in glomerular diseases, we then examined the common regulation of the genes in GCNet in the context of five glomerular diseases based on their transcriptomic data. As a result, twenty-one cytoskeleton components as potential candidate were highlighted for consistently down- or up-regulating in all five glomerular diseases. And then, these candidates were examined in relation to existing known glomerular diseases and genes to determine their possible functions and interactions. In addition, the mRNA levels of these candidates were also validated in a puromycin aminonucleoside(PAN) induced rat nephropathy model and were also matched with existing Diabetic Nephropathy (DN) transcriptomic data. As a result, there are 15 of 21 candidates in PAN induced nephropathy model were consistent with our predication and also 12 of 21 candidates were matched with differentially expressed genes in the DN transcriptomic data. By providing a novel interaction network and prediction, GCNet

  17. Changes of the glomerular size during the human fetal kidney development

    Directory of Open Access Journals (Sweden)

    Daković-Bjelaković Marija

    2006-01-01

    Full Text Available Introduction. Newborns adaptation on postnatal conditions includes significant morphological and functional renal changes. Every kidney contains a constant number of nephrons, at the end of the nephrogenesis period, which extends from week 8 to 34 of gestation. Mature juxtamedullary nephrons possess higher filtration capacity than primitive superficial nephrons, which have insufficient vascularization. Objective. The objective of the study was to calculate an average glomerular diameter in cortical zones of the kidney during development, to define periods of their most intensive growth, and to record differences of glomerular size between different cortical zones. METHOD A total of 30 human fetal kidneys aged from IV to X lunar months were analyzed. Stereological methods were used for calculating the average glomerular diameter in superficial, intermediate and juxtamedullary zone of the kidney cortex. Results. Glomeruli in the superficial cortical zone had the lowest average diameter. The average glomerular diameter continually increased from IV lunar month (0.057±0.004 mm to X lunar month (0.082±0.004 mm, with highly significant correlation with gestational age (r=0.755; p<0.01. The average glomerular diameter in the intermediate zone increased from 0.081±0.004 mm (IV lunar month to 0.096±0.004 mm (X lunar month with low linear correlation with gestational age (r=0.161. Juxtamedullary glomeruli were the biggest ones. Their average diameter, during the IV LM ranged from 0.093±0.006 mm to 0.101±0.004 mm. In the newborns (X lunar month, juxtamedullary glomeruli had spherical structures with an average diameter of 0.103±0.004 mm, and low negative correlation (r=-0.032 with gestational age. In the IV and V lunar months of gestation, there was significant difference (p<0.01; p<0.05 between the average glomerular diameter in the different zones of the kidney cortex. Conclusion. Superficial glomeruli had the smallest diameter, while

  18. Molecular Modeling of Nafion Permselective Membranes

    National Research Council Canada - National Science Library

    Vishnyakov, Aleksey M; Neimark, Alexander V

    2005-01-01

    .... We developed molecular models for Nafion and nerve agent simulant DMMP and explored microphase segregation and mechanisms of DMMP sorption and transport in hydrated membranes with K+ counterion...

  19. Anion permselective membrane. [For redox fuel cells

    Energy Technology Data Exchange (ETDEWEB)

    Alexander, S.S.; Hodgdon, R.B.

    1978-01-01

    Experimental anion permeselective membranes were improved and characterized for use as separators in a chemical redox, power storage cell being developed at the NASA Lewis Research Center. The goal of minimal Fe/sup +3/ ion transfer was achieved for each candidate membrane system. Minimal membrane resistivity was demonstrated by reduction of film thickness using synthetic backing materials but usefulness of thin membranes was limited by the scarcity of compatible fabrics. The most durable and useful backing fabrics were modacrylics. One membrane, a copolymer of 4 vinylpyridine and vinyl benzylchloride was outstanding in overall electrochemical and physical properties. Long term (1000 hrs) membrane chemical and thermal durability in redox environment was shown by three candidate polymers and two membranes. The remainder had good durability at ambient temperature. Manufacturing capability was demonstrated for large scale production of membrane sheets 5.5 ft/sup 2/ in area for two candidate systems.

  20. Loss of glomerular polyanion correlated with albuminuria in experimental cadmium nephropathy

    Energy Technology Data Exchange (ETDEWEB)

    Bernard, A.; Lauwerys, R.; Ouled Amor, A. (Catholic Univ. of Louvain, Brussels (Belgium). Unit of Industrial Toxicology and Occupational Medicine)

    1992-04-01

    The relationship between proteinuria and glomerular polyanion (GPA) charge has been studied in a model of experimental cadmium (Cd) nephropathy. Female Sprague-Dawley rats were administered Cd in drinking water for up to 18 months. From month 2, the animals showed an elevation of albuminuria preceding by about 6 months the rise of urinary [beta][sub 2]-microglobulin and IgG. The nephrotoxic action of Cd was not readily detectable on the basis of the urinary output of [beta]-N-acetylglucosaminidase, alanine aminopeptidase and lactate dehydrogenase. The enzymes showed either little variation or were affected late in the intoxication process. Administration of Cd for 12 or 18 months did not impair the GFR. The glomerular origin of the albuminuria induced by Cd was demonstrated by estimating the glomerular filtration of rat or human (injected intravenously) albumin in rats whose tubular reabsorption had been blocked by a saturating dose of cytochrome C. The GPA charge was assessed by measuring the binding of the cationic dye, Alcian blue (AB), to membranes of isolated glomeruli. The sialic and sulfate content of these membranes was also determined. The Cd induced-albuminuria was negatively correlated with the AB binding to glomerular membranes, their sialic acid content but not with their sulfate content. A negative correlation was also observed between the albuninaria and red blood cell membrane negative charges largely contributed by sialic acid. All these observations can be interpreted as the evidence that Cd enhances the glomerular filtration of proteins through a GPA depletion involving mainly sialic acid. (orig.).

  1. Laminin α2-mediated focal adhesion kinase activation triggers Alport glomerular pathogenesis.

    Directory of Open Access Journals (Sweden)

    Duane Delimont

    Full Text Available It has been known for some time that laminins containing α1 and α2 chains, which are normally restricted to the mesangial matrix, accumulate in the glomerular basement membranes (GBM of Alport mice, dogs, and humans. We show that laminins containing the α2 chain, but not those containing the α1 chain activates focal adhesion kinase (FAK on glomerular podocytes in vitro and in vivo. CD151-null mice, which have weakened podocyte adhesion to the GBM rendering these mice more susceptible to biomechanical strain in the glomerulus, also show progressive accumulation of α2 laminins in the GBM, and podocyte FAK activation. Analysis of glomerular mRNA from both models demonstrates significant induction of MMP-9, MMP-10, MMP-12, MMPs linked to GBM destruction in Alport disease models, as well as the pro-inflammatory cytokine IL-6. SiRNA knockdown of FAK in cultured podocytes significantly reduced expression of MMP-9, MMP-10 and IL-6, but not MMP-12. Treatment of Alport mice with TAE226, a small molecule inhibitor of FAK activation, ameliorated fibrosis and glomerulosclerosis, significantly reduced proteinuria and blood urea nitrogen levels, and partially restored GBM ultrastructure. Glomerular expression of MMP-9, MMP-10 and MMP-12 mRNAs was significantly reduced in TAE226 treated animals. Collectively, this work identifies laminin α2-mediated FAK activation in podocytes as an important early event in Alport glomerular pathogenesis and suggests that FAK inhibitors, if safe formulations can be developed, might be employed as a novel therapeutic approach for treating Alport renal disease in its early stages.

  2. Smart parking barrier

    KAUST Repository

    Alharbi, Abdulrazaq M.

    2016-05-06

    Various methods and systems are provided for smart parking barriers. In one example, among others, a smart parking barrier system includes a movable parking barrier located at one end of a parking space, a barrier drive configured to control positioning of the movable parking barrier, and a parking controller configured to initiate movement of the parking barrier, via the barrier drive. The movable parking barrier can be positioned between a first position that restricts access to the parking space and a second position that allows access to the parking space. The parking controller can initiate movement of the movable parking barrier in response to a positive identification of an individual allowed to use the parking space. The parking controller can identify the individual through, e.g., a RFID tag, a mobile device (e.g., a remote control, smartphone, tablet, etc.), an access card, biometric information, or other appropriate identifier.

  3. Reduced adenosine A2a receptor-mediated efferent arteriolar vasodilation contributes to diabetes-induced glomerular hyperfiltration.

    Science.gov (United States)

    Persson, Patrik; Hansell, Peter; Palm, Fredrik

    2015-01-01

    Diabetes is associated with increased risk for development of kidney disease, and an increased glomerular filtration rate is an early indication of altered kidney function. Here we determine whether reduced adenosine A2a receptor-mediated vasodilation of the efferent arteriole contributes to the increased glomerular filtration rate in diabetes. The glomerular filtration rate, renal blood flow, and proximal tubular stop flow pressure were investigated in control and streptozotocin-diabetic rats during baseline and after administration of the adenosine A2a receptor antagonist ZM241385 or the adenosine A2a receptor agonist CGS21680. The diabetes-induced glomerular hyperfiltration was reduced by 24% following A2a receptor stimulation but was unaffected by A2a receptor inhibition. Contrarily, glomerular filtration rate in controls increased by 22% after A2a receptor inhibition and was unaffected by A2a stimulation. The increased glomerular filtration rate after A2a receptor inhibition in controls and decreased glomerular filtration rate after A2a receptor activation in diabetics were caused by increased and decreased stop flow pressure, respectively. None of the interventions affected renal blood flow. Thus, the normal adenosine A2a receptor-mediated tonic vasodilation of efferent arterioles is abolished in the diabetic kidney. This causes increased efferent arteriolar resistance resulting in increased filtration fraction and hyperfiltration.

  4. Optimization of Gate's technique for measurement of glomerular filtration rate during routine renal scan

    International Nuclear Information System (INIS)

    Zakavi, R.; Momennejad, M.; Soleimani, K.

    2002-01-01

    Using gate's technique for glomerular filtration rate measurement with Gamma camera, the patient is received 5 mCi of Tc-99m-DTPA. By this amount of radioactivity, good quality renal scan is not possible. This study tries to optimize gate's technique for glomerular filtration rate measurement during routing renal scan (with 10-15 mCi). Methods and materials: Scanning was performed for 60 seconds from samples of Tc-99m with activities of 3, 9, 12, 15 and 18 mCi in a small syringe, with a 30 cm distance from the detector. Another sample of mCi of Tc-99m was imaged for 5, 10, 15, 20 and 30 seconds. The same sample was again imaged for 10 seconds in different distances (10, 20, 30 and 40 cm) from the detector. Each image was acquired 10 times. Using rectangular region of interest, total count and maximum count per pixel were recorded for all images. Results: The total count revealed rising in the images form 3 mCi to 15 mCi samples while declining thereafter, suggesting paralysis of the Gamma camera in high activities. Maximum count per pixel was 32767 (2 in 15 power minus one ) in all images except for the 3 mCi sample image, suggesting saturation of the pixels in high activities. Also saturation of the pixels was noted in images of 12 mCi sample for more than 15 seconds. No saturation of pixels was noticed within 20-40 cm distance from the detector. Conclusion: By optimization of the Gate's technique for glomerular filtration rate measurement, glomerular filtration Rate can be calculated during routine renal scan. We suggest using 10-15 mCi of Tc-99 m-DTPA, with 5-15 seconds pre injected syringe count, 30 cm distant from the detector. Comparison of glomerular filtration rate calculation using suggested technique with glomerular filtration rate estimation by creatinine clearance in 9 patients, resulted in a significant and good correlation coefficient. (R=0.883, P=0.005)

  5. Safety-barrier diagrams

    DEFF Research Database (Denmark)

    Duijm, Nijs Jan

    2007-01-01

    are discussed. A simple method for quantification of safety-barrier diagrams is proposed, including situations where safety barriers depend on shared common elements. It is concluded that safety-barrier diagrams provide a useful framework for an electronic data structure that integrates information from risk...

  6. Measurement of the plasma clearance of urographic contrast media for the determination of glomerular filtration rate

    International Nuclear Information System (INIS)

    O'Reilly, P.H.; Jones, D.A.; Farah, N.B.

    1988-01-01

    Further experience with a new method to determine glomerular filtration rate is presented. The method depends on measurement by an x-ray fluorescence technique of the plasma disappearance of the injected iodine in standard nonionic radiographic contrast media used during excretory urography. The results of comparison of contrast clearance with /sup 99m/technetium-diethylenetriaminepentaacetic acid clearance in 33 cases showed excellent agreement with a correlation coefficient of 0.95. Reproducibility of the contrast clearance method was confirmed by repeated examination of 10 plasma samples at weekly intervals for 6 weeks, the results of which showed no significant differences. The contrast clearance technique for the measurement of glomerular filtration rate during excretory urography is simple, quick and accurate, and merits further development

  7. Dynamic 99mTc-DTPA renal gammagraphy with glomerular filtration rate determination

    International Nuclear Information System (INIS)

    Vivodova, M.; Hupka, S.; Michalko, J.; Lehotska, V.; Pipa, V.; Hasik, E.; Tomek, D.

    1989-01-01

    Using the method of 99m Tc-DTPA (diethylenetriaminepentaacetic acid) sequential renal gammagraphy with subsequent glomerular filtration rate determination by means of a gamma camera and a computer, a total of 285 patients were examined with suspected renal and urinary tract diseases, subjects after surgery on these organs or those serving as controls after drug therapy. With the help of a modified application computer program, a study was designed to evaluate quantitatively some functional parameters and to determine the total and the separate glomerular filtration rate values by 99m Tc-DTPA according to Gates. The benefits of the method are that it is non-invasive, rapid, atraumatic, with low exposure to radiation while offering a broad range of applications in routine diagnostic practice of nephrology, and especially so in pediatric patients. (author). 7 figs., 3 tabs., 18 refs

  8. Measurement of renal glomerular filtration rate using labelled substances with compartmental analysis

    International Nuclear Information System (INIS)

    Eberstadt, P.L.

    1981-10-01

    Using a model for the two-compartmental open system and experiments on animals (rabbits and dogs) as well as on human healthy volunteers, an attempt was made to study the advantages and limitations of different radionuclide methods for glomerular filtration rate determination. Labelled compounds used in different combinations were: 3 H-inulin, sup(113m)In-EDTA, 131 I-iothalamate, sup(99m)Tc-DTPA and 14 C-creatinine. The results of the study lead to some working hypotheses concerning the value of creatinine and other labelled substances in the measurement of glomerular filtration rate in clinical practice. The advantages and disadvantages of individual methods summarized in the final report are generally in agreement with the present views of many research workers. Also the hypothesis can be justified that the different labelled compounds which have been studied might be handled independently by the membranes involved but at the long run produce similar homeostatic balance

  9. Cell renewal of glomerular cell types in normal rats. An autoradiographic analysis

    International Nuclear Information System (INIS)

    Pabst, R.; Sterzel, R.B.

    1983-01-01

    Normal adult Sprague-Dawley rats received either a single or repetitive injection of the DNA precursor 3 H-thymidine ( 3 H-TdR). For autoradiography semi-thin sections were prepared 2 hr to 14 days after labeling. The majority of labeled cells noted in glomerular tufts were endothelial cells. Mesangial cells had a lower production rate. Podocytes revealed no evidence of proliferation. Bowman's capsule cells showed a higher labeling index than tuft cells at all times. Neither the urinary nor the vascular pole was found to be a proliferative zone for Bowman's capsule cells. The flash and repetitive labeling experiments demonstrated a constant rate of cell renewal of about 1% per day, resulting in a long life span for endothelial and mesangial cells as well as Bowman's capsule cells. These data provide a basis for cell kinetic studies in models of glomerular diseases

  10. Glomerular lesions in Aleutian disease of mink (Mustela vison): a morphological and differential morphometrical study.

    Science.gov (United States)

    Nieto, J M; Alvarez, C; Flores, J M; Romano, J

    1991-04-01

    A morphological and morphometrical study has been carried out on glomerular lesions in mink with spontaneous Aleutian disease, using the WHO classification for Systemic Lupus Erytematous Nefritis. 154 renal samples from sick animals and 10 samples from uninfected mink were processed by routine histopathological techniques and metacrylate inclusions. The samples were studied quantitatively with an automatic image analyzer. 5 forms of glomerulonephritis (GN) were identified: mesangial glomerulonephritis (n = 13), focal and segmental GN (n = 10), diffuse GN (n = 99), membranous GN (n = 12) and advanced sclerosing GN (n = 10) and were associated with the degree of interstitial plasmocytosis. Glomerule morphometry was shown to be an excellent method for identifying the type of lesion, while it quantified the participation of various glomerular elements in the lesion.

  11. Anthocyanin-rich purple corn extract inhibit diabetes-associated glomerular angiogenesis.

    Directory of Open Access Journals (Sweden)

    Min-Kyung Kang

    Full Text Available Diabetic nephropathy (DN is one of the major diabetic complications and the leading cause of end-stage renal disease. Abnormal angiogenesis results in new vessels that are often immature and play a pathological role in DN, contributing to renal fibrosis and disrupting glomerular failure. Purple corn has been utilized as a daily food and exerts disease-preventive activities. This study was designed to investigate whether anthocyanin-rich purple corn extract (PCE prevented glomerular angiogenesis under hyperglycemic conditions. Human endothelial cells were cultured in conditioned media of mesangial cells exposed to 33 mM high glucose (HG-HRMC-CM. PCE decreased endothelial expression of vascular endothelial growth factor (VEGF and hypoxia inducible factor (HIF-1α induced by HG-HRMC-CM. Additionally, PCE attenuated the induction of the endothelial marker of platelet endothelial cell adhesion molecule (PECAM-1 and integrin β3 enhanced in HG-HRMC-CM. Endothelial tube formation promoted by HG-HRMC-CM was disrupted in the presence of PCE. In the in vivo study employing db/db mice treated with 10 mg/kg PCE for 8 weeks, PCE alleviated glomerular angiogenesis of diabetic kidneys by attenuating the induction of VEGF and HIF-1α. Oral administration of PCE retarded the endothelial proliferation in db/db mouse kidneys, evidenced by its inhibition of the induction of vascular endothelium-cadherin, PECAM-1 and Ki-67. PCE diminished the mesangial and endothelial induction of angiopoietin (Angpt proteins under hypeglycemic conditions. The induction and activation of VEGF receptor 2 (VEGFR2 were dampened by treating PCE to db/db mice. These results demonstrate that PCE antagonized glomerular angiogenesis due to chronic hyperglycemia and diabetes through disturbing the Angpt-Tie-2 ligand-receptor system linked to renal VEGFR2 signaling pathway. Therefore, PCE may be a potent therapeutic agent targeting abnormal angiogenesis in DN leading to kidney failure.

  12. Predictive performance of 12 equations for estimating glomerular filtration rate in severely obese patients

    Directory of Open Access Journals (Sweden)

    Ary Serpa Neto

    2011-09-01

    Full Text Available Objective: Considering that the Cockcroft-Gault formula and theequation of diet modification in renal disease are amply used in clinical practice to estimate the glomerular filtration rate, although they seem to have low accuracy in obese patients, the present study intends to evaluate the predictive performance of 12 equations used to estimate the glomerular filtration rate in obese patients. Methods: This is a cross-sectional retrospective study, conducted between 2007 and 2008 and carried out at a university, of 140 patients with severe obesity (mean body mass index 44 ± 4.4 kg/m2. The glomerular filtration rate was determined by means of 24-hour urine samples. Patients were classified into one or more of the four subgroups: impaired glucose tolerance (n = 43, diabetic (n = 24, metabolic syndrome (n = 76, and/or hypertension (n = 66. We used bias, precision, and accuracy to assess the predictive performance of each equation in the entire group and in the subgroups. Results: In renal disease, Cockcroft-Gault’s formula and the diet modification equation are not precise in severely obese patients (precision: 40.9 and 33.4, respectively. Sobh’s equationshowed no bias in the general group or in two subgroups. Salazar-Corcoran’s and Sobh’s equations showed no bias for the entire group(Bias: -5.2, 95% confidence interval (CI = -11.4, 1.0, and 6. 2; 95%CI = -0.3, 12.7, respectively. All the other equations were imprecise for the entire group. Conclusion: Of the equations studied, those of Sobh and Salazar-Corcoran seem to be the best for estimating the glomerular filtration rate in severely obese patients analyzed in our study.

  13. Glomerular Filtration Rate Estimation by Serum Creatinine or Serum Cystatin C in Preterm (<31 Weeks) Neonates.

    Science.gov (United States)

    Garg, Parvesh; Hidalgo, Guillermo

    2017-06-15

    Glomerular filtration rate (GFR) was estimated by serum creatinine (Schwartz's equation) and serum cystatin C (Filler's equation) in preterm neonates (24-31 weeks of gestation) in a prospective cohort study. Serum creatinine and cystatin C was obtained at birth and then every two weeks during the first month. We found a poor fit between two methods, and a steadier GFR assessment by cystatin C.

  14. Radiation induced changes in the expression of fibronectin, Pai-1, MMP in rat glomerular epithelial cell

    International Nuclear Information System (INIS)

    Park, Woo Yoon; Kim, Won Dong; Zheng, Ying; Ha, Tae Sun; Kim, Jae Sung; Cho, Moon June

    2006-01-01

    Renal irradiation can lead to the development of radiation nephropathy, and this is characterized by the accumulation of extracellular matrix and final fibrosis. To determine the possible role of the glomerular epithelial cell, the radiation-induced changes in the expression of its genes associated with the extracellular matrix were analyzed. Rat glomerular epithelial cells (GEpC) were irradiated with a single dose of 0, 2, 5, 10 and 20 Gy with using 6 MV LINAC (Siemens, USA), and the samples were collected 6, 24, 48 and 72 hours post-irradiation, respectively. Northern blotting, western blotting and zymography were used to measure the expression level of fibronectin (Fn), plasminogen activator inhibitor-1 (Pai-1), matrix metalloproteinases-2, 9 (MMP-2, 9), tissue inhibitor of metalloproteinases-2 (TIMP-2), tissue-type plasminogen activator (t-PA) and urokinase-type plasminogen activator (u-PA). Irradiation with a single dose of 10 Gy resulted in a significant increase in Fn mRNA since 24 hours post-irradiation, and a single dose of 5 and 10 Gy significantly increased the Fn immunoreactive protein measured 48 hours post-irradiation. An increase in Pai-mRNA and protein was also observed and especially, a single dose of 10 Gy significantly increased the mRNA measured 24 and 48 hours post-irradiation. The active MMP-2 measured 24 hours post-irradiation slightly increased in a dose dependent manner, but this increase did not reach statistical significance. The levels of MMP-9, TIMP-2, t-PA and u-PA appeared unaltered after irradiation. Irradiation of the glomerular epithelial cells altered the expression of genes associated with the extracellular matrix, implying that the glomerular epithelial cell may be involved in the development of radiation nephropathy

  15. Radiation induced changes in the expression of fibronectin, Pai-1, MMP in rat glomerular epithelial cell

    Energy Technology Data Exchange (ETDEWEB)

    Park, Woo Yoon; Kim, Won Dong; Zheng, Ying; Ha, Tae Sun [Chungbuk National University, Cheongju (Korea, Republic of); Kim, Jae Sung [Seoul National University, Seoul (Korea, Republic of); Cho, Moon June [Chungnam National University, Daejeon (Korea, Republic of)

    2006-03-15

    Renal irradiation can lead to the development of radiation nephropathy, and this is characterized by the accumulation of extracellular matrix and final fibrosis. To determine the possible role of the glomerular epithelial cell, the radiation-induced changes in the expression of its genes associated with the extracellular matrix were analyzed. Rat glomerular epithelial cells (GEpC) were irradiated with a single dose of 0, 2, 5, 10 and 20 Gy with using 6 MV LINAC (Siemens, USA), and the samples were collected 6, 24, 48 and 72 hours post-irradiation, respectively. Northern blotting, western blotting and zymography were used to measure the expression level of fibronectin (Fn), plasminogen activator inhibitor-1 (Pai-1), matrix metalloproteinases-2, 9 (MMP-2, 9), tissue inhibitor of metalloproteinases-2 (TIMP-2), tissue-type plasminogen activator (t-PA) and urokinase-type plasminogen activator (u-PA). Irradiation with a single dose of 10 Gy resulted in a significant increase in Fn mRNA since 24 hours post-irradiation, and a single dose of 5 and 10 Gy significantly increased the Fn immunoreactive protein measured 48 hours post-irradiation. An increase in Pai-mRNA and protein was also observed and especially, a single dose of 10 Gy significantly increased the mRNA measured 24 and 48 hours post-irradiation. The active MMP-2 measured 24 hours post-irradiation slightly increased in a dose dependent manner, but this increase did not reach statistical significance. The levels of MMP-9, TIMP-2, t-PA and u-PA appeared unaltered after irradiation. Irradiation of the glomerular epithelial cells altered the expression of genes associated with the extracellular matrix, implying that the glomerular epithelial cell may be involved in the development of radiation nephropathy.

  16. Decrease of Glomerular Filtration Rate may be Attributed to the Microcirculation Damage in Renal Artery Stenosis

    Directory of Open Access Journals (Sweden)

    Hao-Jian Dong

    2015-01-01

    Full Text Available Background: The decrease of glomerular filtration rate has been theoretically supposed to be the result of low perfusion in renal artery stenosis (RAS. But the gap between artery stenosis and the glomerular filtration ability is still unclear. Methods: Patients with selective renal artery angiogram were divided by the degree of renal artery narrowing, level of estimated glomerular filtration rate (eGFR, respectively. The different levels of eGFR, renal microcirculation markers, and RAS severity were compared with each other, to determine the relationships among them. Results: A total of 215 consecutive patients were enrolled in the prospective cohort study. Concentrations of microcirculation markers had no significant difference between RAS group (RAS ≥ 50% and no RAS group (RAS < 50% or did not change correspondingly to RAS severity. The value of eGFR in RAS group was lower than that in the no RAS group, but it did not decline parallel to the progressive severity of RAS. The microcirculation markers presented integral difference if grouped by different eGFR level with negative tendency, especially that plasma cystatin C (cysC and urinary microalbumin to creatinine ratio (mACR increased with the deterioration of eGFR, with strong (r = −0.713, P < 0.001 and moderate (r = −0.580, P < 0.001 correlations. In the subgroup analysis of severe RAS (RAS ≥ 80%, the levels of plasma cysC and urinary mACR demonstrated stronger negative associations with eGFR, (r = −0.827, P < 0.001 and (r = −0.672, P < 0.001 correlations, respectively. Conclusions: Severity of RAS could not accurately predict the value of eGFR, whereas microcirculation impairment may substantially contribute to the glomerular filtration loss in patients with RAS.

  17. Skin barrier function

    DEFF Research Database (Denmark)

    2016-01-01

    barrier integrity, factors influencing the penetration of the skin, influence of wet work, and guidance for prevention and saving the barrier. Distinguished researchers have contributed to this book, providing a comprehensive and thorough overview of the skin barrier function. Researchers in the field...... on the subject. It covers new basic research on skin markers, including results on filaggrin and on methods for the assessment of the barrier function. Biological variation and aspects of skin barrier function restoration are discussed as well. Further sections are dedicated to clinical implications of skin...

  18. Safety- barrier diagrams

    DEFF Research Database (Denmark)

    Duijm, Nijs Jan

    2008-01-01

    trees and Bayesian networks is discussed. A simple method for quantification of safety-barrier diagrams is proposed. It is concluded that safety-barrier diagrams provide a useful framework for an electronic data structure that integrates information from risk analysis with operational safety management.......Safety-barrier diagrams and the related so-called 'bow-tie' diagrams have become popular methods in risk analysis. This paper describes the syntax and principles for constructing consistent and valid safety-barrier diagrams. The relation of safety-barrier diagrams to other methods such as fault...

  19. Detection of activated parietal epithelial cells on the glomerular tuft distinguishes early focal segmental glomerulosclerosis from minimal change disease

    NARCIS (Netherlands)

    Smeets, B.; Stucker, F.; Wetzels, J.; Brocheriou, I.; Ronco, P.; Grone, H.J.; D'Agati, V.; Fogo, A.B.; Kuppevelt, T.H. van; Fischer, H.P.; Boor, P.; Floege, J.; Ostendorf, T.; Moeller, M.J.

    2014-01-01

    In rodents, parietal epithelial cells (PECs) migrating onto the glomerular tuft participate in the formation of focal segmental glomerulosclerosis (FSGS) lesions. We investigated whether immunohistologic detection of PEC markers in the initial biopsies of human patients with first manifestation of

  20. Glomerular filtration rate estimated from the uptake phase of 99mTc-DTPA renography in chronic renal failure

    DEFF Research Database (Denmark)

    Petersen, L J; Petersen, J R; Talleruphuus, U

    1999-01-01

    The purpose of the study was to compare the estimation of glomerular filtration rate (GFR) from 99mTc-DTPA renography with that estimated from the renal clearance of 51Cr-EDTA, creatinine and urea....

  1. Pregnancy enhances the sensitivity of glomerular ecto-adenosine triphosphate-diphosphohydrolase to products of activated polymorphonuclear leukocytes

    NARCIS (Netherlands)

    Faas, MM; Bakker, WW; Baller, JFW; Schuiling, GA

    To test the hypothesis that pregnancy enhances the sensitivity of glomerular ecto-adenosine triphosphate-diphosphohydrolase to products of activated polymorphonuclear leukocytes, cryostat-cut kidney sections of pregnant and cycling rats were exposed to activated polymorphonuclear leukocytes and

  2. Measurement of glomerular filtration rate in connection with renography with 99mTc-DTPA

    International Nuclear Information System (INIS)

    Cappelen, T.; Skretting, A.; Winderen, M.; Aas, M.

    1999-01-01

    Glomerular filtration rate (GFR) was measured in two groups of cancer patients. In 20 patients, glomerular filtration rate was measured simultaneously with 51 Cr-EDTA, 99m Tc-DTPA and the X-ray contrast agent iohexol as markers, and with a complete set of eight blood samples during 24 hours. In a second group of 120 patients, the authors used 99m TC-DTPA only and tested various simplified methods, based on one or two blood samples. Glomerular filtration rate was also calculated from serum creatinine. There was excellent agreement between the values measured with the three markers and in the same group of patients very good agreement with the results of simplified methods. The larger study carried out with 99m Tc-DTPA on the second group of patients confirmed a very good agreement between methods based on the slope of the plasma curve and a method based on one blood sample only. The correlation was worse between the values obtained by any of the radionuclide methods and those calculated from serum creatinine. The latter method should therefore not be used for determination of renal function

  3. Autoantibodies targeting glomerular annexin A2 identify patients with proliferative lupus nephritis.

    Science.gov (United States)

    Caster, Dawn J; Korte, Erik A; Merchant, Michael L; Klein, Jon B; Wilkey, Daniel W; Rovin, Brad H; Birmingham, Dan J; Harley, John B; Cobb, Beth L; Namjou, Bahram; McLeish, Kenneth R; Powell, David W

    2015-12-01

    Patients with systemic lupus erythematosus (SLE) frequently develop lupus nephritis (LN), a complication frequently leading to end stage kidney disease. Immune complex deposition in the glomerulus is central to the development of LN. Using a targeted proteomic approach, we tested the hypothesis that autoantibodies targeting glomerular antigens contribute to the development of LN. Human podocyte and glomerular proteins were separated by SDS-PAGE and immunoblotted with sera from SLE patients with and without LN. The regions of those gels corresponding to reactive bands observed with sera from LN patients were analyzed using LC-MS/MS. LN reactive bands were seen at approximately 50 kDa in podocyte extracts and between 36 and 50 kDa in glomerular extracts. Those bands were analyzed by LC-MS/MS and 102 overlapping proteins were identified. Bioinformatic analysis determined that 36 of those proteins were membrane associated, including a protein previously suggested to contribute to glomerulonephritis and LN, annexin A2. By ELISA, patients with proliferative LN demonstrated significantly increased antibodies against annexin A2. Proteomic approaches identified multiple candidate antigens for autoantibodies in patients with LN. Serum antibodies against annexin A2 were significantly elevated in subjects with proliferative LN, validating those antibodies as potential biomarkers. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Early B cell factor 1 is an essential transcription factor for postnatal glomerular maturation

    Science.gov (United States)

    Fretz, Jackie A.; Nelson, Tracy; Velazquez, Heino; Xi, Yougen; Moeckel, Gilbert; Horowitz, Mark C.

    2013-01-01

    The coordination of multiple cytokines and transcription factors with their downstream signaling pathways have been shown to be integral to nephron maturation. Here we present a completely novel role for the helix-loop-helix transcription factor Early B cell Factor 1 (Ebf1), originally identified for B cell maturation, for the proper maturation of glomerular cells from mesenchymal progenitors. The expression of Ebf1 was both spatially and temporally regulated within the developing cortex and glomeruli. Using Ebf1-null mice we then identified biochemical, metabolic, and histological abnormalities in renal development that arose in the absence of this transcription factor. In the Ebf1 knockout mice the developed kidneys show thinned cortices and reduced glomerular maturation. The glomeruli showed abnormal vascularization and severely effaced podocytes. The mice exhibited early albuminuria and elevated blood urea nitrogen levels. Moreover, the GFR was reduced over 66 percent and the expression of podocyte-derived VEGF-A was decreased compared to wild type control mice. Thus, Ebf1 has a significant and novel role in glomerular development, podocyte maturation, and the maintenance of kidney integrity and function. PMID:24172684

  5. Estimation of single-kidney glomerular filtration rate without exogenous contrast agent.

    Science.gov (United States)

    He, Xiang; Aghayev, Ayaz; Gumus, Serter; Ty Bae, K

    2014-01-01

    Measurement of single-kidney filtration fraction and glomerular filtration rate (GFR) without exogenous contrast is clinically important to assess renal function and pathophysiology, especially for patients with comprised renal function. The objective of this study is to develop a novel MR-based tool for noninvasive quantification of renal function using conventional MR arterial spin labeling water as endogenous tracer. The regional differentiation of the arterial spin labeling water between the glomerular capsular space and the renal parenchyma was characterized and measured according to their MR relaxation properties (T1ρ or T2 ), and applied to the estimation of filtration fraction and single-kidney GFR. The proposed approach was tested to quantify GFR in healthy volunteers at baseline and after a protein-loading challenge. Biexponential decay of the cortical arterial spin labeling water MR signal was observed. The major component decays the same as parenchyma water; the minor component decays much slower as expected from glomerular ultra-filtrates. The mean single-kidney GFR was estimated to be 49 ± 9 mL/min at baseline and increased by 28% after a protein-loading challenge. We developed an arterial spin labeling-based MR imaging method that allows us to estimate renal filtration fraction and singe-kidney GFR without use of exogenous contrast. Copyright © 2013 Wiley Periodicals, Inc.

  6. Glomerular parietal epithelial cell activation induces collagen secretion and thickening of Bowman's capsule in diabetes.

    Science.gov (United States)

    Holderied, Alexander; Romoli, Simone; Eberhard, Jonathan; Konrad, Lukas A; Devarapu, Satish K; Marschner, Julian A; Müller, Susanna; Anders, Hans-Joachim

    2015-03-01

    The metabolic and hemodynamic alterations in diabetes activate podocytes to increase extracellular matrix (ECM) production, leading to thickening of the glomerular basement membrane (GBM). We hypothesized that diabetes would activate parietal epithelial cells (PECs) in a similar manner and cause thickening of Bowman's capsules. Periodic acid Schiff staining of human kidney biopsies of 30 patients with diabetic nephropathy (DN) revealed a significantly thicker Bowman's capsule as compared with 20 non-diabetic controls. The average thickness was 4.55±0.21 μm in the group of patients with DN compared with 2.92±0.21 μm in the group of non-diabetic controls (PBowman's capsule showed strong association with CD44-positive PECs. In summary, metabolic alterations in diabetes activate PECs to increase the expression and secretion of Bowman's capsule proteins. This process may contribute to the thickening of the Bowman's capsule, similar to the thickening of the GBM that is driven by activated podocytes. These data may also imply that activated PECs contribute to ECM production once they migrate to the glomerular tuft, a process resulting in glomerular scaring, for example, in diabetic glomerulosclerosis.

  7. Common histological patterns in glomerular epithelial cells in secondary focal segmental glomerulosclerosis.

    Science.gov (United States)

    Kuppe, Christoph; Gröne, Hermann-Josef; Ostendorf, Tammo; van Kuppevelt, Toin H; Boor, Peter; Floege, Jürgen; Smeets, Bart; Moeller, Marcus J

    2015-11-01

    Parietal epithelial cells (PECs) are involved in the development of sclerotic lesions in primary focal and segmental glomerulosclerosis (FSGS). Here, the role of PECs was explored in the more common secondary FSGS lesions in 68 patient biopsies, diagnosed with 11 different frequently or rarely encountered glomerular pathologies and additional secondary FSGS lesions. For each biopsy, one section was quadruple stained for PECs (ANXA3), podocytes (synaptopodin), PEC matrix (LKIV69), and Hoechst (nuclei), and a second was quadruple stained for activated PECs (CD44 and cytokeratin-19), PEC matrix, and nuclei. In all lesions, cellular adhesions (synechiae) between Bowman's capsule and the tuft were formed by cells expressing podocyte and/or PEC markers. Cells expressing PEC markers were detected in all FSGS lesions independent of the underlying glomerular disease and often stained positive for markers of activation. Small FSGS lesions, which were hardly identified on PAS sections previously, were detectable by immunofluorescent staining using PEC markers, potentially improving the diagnostic sensitivity to identify these lesions. Thus, similar patterns of cells expressing podocyte and/or PEC markers were found in the formation of secondary FSGS lesions independent of the underlying glomerular disease. Hence, our findings support the hypothesis that FSGS lesions follow a final cellular pathway to nephron loss that includes involvement of cells expressing PEC markers.

  8. Effects of a K+ channel blocker on glomerular filtration rate and electrolyte excretion in conscious rats.

    Science.gov (United States)

    Ludens, J H; Clark, M A; Lawson, J A

    1995-06-01

    Effects of a K+ channel blocker on glomerular filtration rate and electrolyte excretion in conscious rats were observed. Effects of K+ channel modulation on glomerular filtration rate and electrolyte excretion were studied using the adenosine-triphosphate- (ATP)-sensitive K+ channel blocker 4-morpholinecarboximidine-N-1-adamantyl-N'-cyclohexylhydr ochloride (U-37883A) in conscious rats previously equipped with catheters for clearance studies. In saline-loaded rats, i.v. doses of U-37883A of 1.7, 5.0 and 15 mg/kg increased absolute and fractional Na+ excretion dose-dependently without changing K+ excretion. The glomerular filtration rate remained constant during diuresis. In water-loaded (hypotonic dextrose) rats, free-water clearance studies revealed that the ATP-sensitive K+ channel blocker significantly decreased an index of solute reabsorption (free-water clearance adjusted for chloride clearance) in the diluting segment during peak natriuretic activity. In addition, U-37883A significantly decreased the osmolality of renal papillary interstitial fluid, indicative of an effect in the medullary portion of the diluting segment. Together, these findings suggest that ATP-sensitive K+ channels, possibly those located at the apical boarder, play a pivotal role in Na+ reabsorption in the thick ascending limb of the loop of Henle.

  9. Cystatin C is a suitable marker of glomerular function in children with cancer.

    Science.gov (United States)

    Bárdi, Edit; Bobok, Ildikó; Oláh, Anna V; Oláh, Eva; Kappelmayer, János; Kiss, Csongor

    2004-10-01

    Antineoplastic chemotherapy is associated with nephrotoxic side effects. Data on nephrotoxicity in childhood cancer are scanty, in part because of the difficulties in obtaining reliable markers of glomerular function. We used serum cystatin C (cysC) to assess glomerular function. CysC was compared with serum creatinine concentration (S(Cr)), the endogenous creatinine clearence ( C(Cr)), and the calculated Counahan formula ( C(Counahan)) in children with leukemia and solid tumors. CysC was measured by particle-enhanced immunoturbidimetric assay. Serum and urinary creatinine concentrations were determined by the Jaffé method. Samples were obtained from 258 children, including 92 receiving anticancer chemotherapy, 108 long-term survivors, 40 children without any renal disease, and 18 patients with chronic renal insufficiency. CysC of patients on current chemotherapy was assessed both before and after treatment. Significant correlations were found between cysC and S(Cr) and between 1/cysC and C( Counahan). CysC increased significantly after cisplatin, methotrexate, cyclophosphamide, ifosfamide, and multimodality treatment. Our results suggest that cysC measurement can be used to characterize glomerular function in children with cancer.

  10. A fine structural localization of the non-specific cholinesterase activity in glomerular nerve formations (endings).

    Science.gov (United States)

    Dubový, P

    1990-01-01

    Snout glabrous skin (rhinarium) of the cat is innervated not only by typical simple lamellar corpuscles but also glomerular formations. In contrast to simple lamellar corpuscles, glomerular nerve formations are located away the dermal papillae. In cross sections, glomerular nerve formation consists of several axonal profiles enveloped by 1-2 cytoplasmic lamellae of Schwann cells. The space among them is filled by collagenous microfibrils and the basal lamina-like material. Capsule was composed from fibroblast-like cells without definite basal lamina. An electron-dense reaction product due to non-specific cholinesterase activity was associated with Schwann cells and their processes surrounding unmyelinated terminal portion of the sensory axons. Abundant reaction product was bound to the collagenous microfibrils and was deposited in extracellular matrix between Schwann cell processes. These results are further evidence for the presence of the non-specific cholinesterase molecules as integral component of the extracellular matrix in sensory corpuscles. On the basis of histochemical study two possible explanation are considered for functional involving of this enzyme in sensory nerve formations.

  11. Safety-barrier diagrams

    DEFF Research Database (Denmark)

    Duijm, Nijs Jan

    2007-01-01

    Safety-barrier diagrams and the related so-called "bow-tie" diagrams have become popular methods in risk analysis. This paper describes the syntax and principles for constructing consistent and valid safety-barrier diagrams. The relation with other methods such as fault trees and Bayesian network...... analysis with operational safety management.......Safety-barrier diagrams and the related so-called "bow-tie" diagrams have become popular methods in risk analysis. This paper describes the syntax and principles for constructing consistent and valid safety-barrier diagrams. The relation with other methods such as fault trees and Bayesian networks...... are discussed. A simple method for quantification of safety-barrier diagrams is proposed, including situations where safety barriers depend on shared common elements. It is concluded that safety-barrier diagrams provide a useful framework for an electronic data structure that integrates information from risk...

  12. Glomerular filtration rate estimated from the uptake phase of 99mTc-DTPA renography in chronic renal failure

    DEFF Research Database (Denmark)

    Petersen, L J; Petersen, J R; Talleruphuus, U

    1999-01-01

    The purpose of the study was to compare the estimation of glomerular filtration rate (GFR) from 99mTc-DTPA renography with that estimated from the renal clearance of 51Cr-EDTA, creatinine and urea.......The purpose of the study was to compare the estimation of glomerular filtration rate (GFR) from 99mTc-DTPA renography with that estimated from the renal clearance of 51Cr-EDTA, creatinine and urea....

  13. Glomerular lipidosis accompanied by renal tubular oxalosis in wild and laboratory-reared Japanese rock ptarmigans (Lagopus mutus japonicus).

    Science.gov (United States)

    Murai, Atsuko; Murakami, Mami; Sakai, Hiroki; Shimizu, Hiroaki; Murata, Koichi; Yanai, Tokuma

    2011-12-01

    Glomerular lipidosis is a disease characterized by lipid accumulation in mesangial cells but that has not been fully investigated in avian species. We examined four wild and two laboratory-reared Japanese rock ptarmigans (Lagopus mutus japonicus)--an endangered avian species--presenting vacuolar deposits in the glomeruli. All cases had vacuolar deposits in the glomeruli. In the wild cases, fewer than 30% of all glomeruli were affected, compared with more than 90% in the laboratory-reared cases. In the wild cases, most deposits were mild and restricted to the mesangial areas of glomeruli. In the laboratory-reared cases, nearly all of the deposits covered entire glomeruli. Electron microscopy of mild deposits revealed vacuoles in the cytoplasm of mesangial cells. These vacuoles were positive for Sudan III, Sudan black B, oil red O, Nile blue, periodic acid-Schiff, Schultz test, and digitonin stain and were negative for performaric acid-Schiff stains. Based on these results, we diagnosed the glomerular lesion as glomerular lipidosis caused by uptake of low-density lipoprotein in mesangial cells. Except for one wild case, all cases exhibited renal tubular oxalosis. The severity of tubular oxalosis tended to be related to the severity of glomerular lipidosis: In cases of mild glomerular lipidosis, tubular oxalosis was also mild or absent. We therefore diagnosed the primary lesion as glomerular lipidosis accompanied by tubular oxalosis. The four wild cases came from different zones and therefore had no opportunities to interbreed and no common relatives. We believe these data support the hypothesis that glomerular lipidosis is a disease of the general population ofJapanese rock ptarmigans. This is the first report of glomerular lipidosis accompanied by renal tubular oxalosis in an avian species.

  14. Glomerular and tubular function during AT1 receptor blockade in pigs with neonatal induced partial ureteropelvic obstruction

    DEFF Research Database (Denmark)

    Eskild-Jensen, Anni; Thomsen, Karsten; Rungø, Christine

    2007-01-01

    Previously, we showed that neonatal induced chronic partial unilateral ureteral obstruction (PUUO) of the multipapillary pig kidney decreased glomerular filtration rate (GFR) of the obstructed kidney. We hypothesized that ANG II and nitric oxide (NO) are important for the changes in renal functio...... is changed by neonatal induced chronic PUUO. This may have diagnostic potential in children with suspected congenital obstruction. Our results also demonstrate compromised tubular functions in response to chronic PUUO despite preservation of glomerular function....

  15. Radiation-induced glomerular thrombus formation and nephropathy are not prevented by the ADP receptor antagonist clopidogrel

    International Nuclear Information System (INIS)

    Poele, Johannes A.M. te; Kleef, Ellen M. van; Wal, Anja F. van der; Dewit, Luc G.H.; Stewart, Fiona A.

    2001-01-01

    Purpose: To assess the effects of kidney irradiation on glomerular adenosine diphosphatase (ADPase) activity and intraglomerular microthrombus formation, and their correlation to the development of renal functional impairment. Methods and Materials: C3H/HenAf-nu + mice were given single-dose or fractionated kidney irradiations. Glomerular ADPase activity was measured using a cerium-based histochemical method. Microthrombus formation within the glomeruli was assessed by a semiquantitative immunohistochemical analysis of fibrinogen/fibrin deposits. Renal function was assessed by the [ 51 Cr]EDTA retention assay. Results: The ADPase activity was significantly reduced, to approximately 50% of pretreatment value, 4-40 weeks after 10-16 Gy single-dose irradiation and at 44 weeks after 20x2 Gy. No dose-effect relationship was found. An approximately fourfold increase in glomerular fibrinogen/fibrin staining was observed at 1 year after irradiation. This increase was not influenced by treating the mice with daily, oral clopidogrel, a platelet ADP receptor antagonist, which reduced platelet aggregation by more than 75%. Radiation-induced impairment of glomerular filtration was also not affected by the clopidogrel treatment. Conclusion: These data indicate that irradiation significantly reduced glomerular ADPase activity, which correlated with an increased glomerular fibrinogen/fibrin deposition. We were not able to reduce these prothrombotic changes, nor to protect against radiation nephropathy, by pharmacological intervention with an ADP-receptor antagonist

  16. Anti-glomerular basement membrane disease superimposed on membranous nephropathy: a case report and review of the literature

    Directory of Open Access Journals (Sweden)

    Nivera Noel

    2010-08-01

    Full Text Available Abstract Introduction Anti-glomerular basement membrane disease is a rare autoimmune disorder characterized by pulmonary hemorrhage, crescentic glomerulonephritis and the presence of circulating anti-glomerular basement membrane antibodies. The simultaneous occurrence of both anti-glomerular basement membrane disease and membranous nephropathy is rare. Case presentation A 59-year-old Hispanic man presented with acute onset of nausea and vomiting and was found to have renal insufficiency. Work-up included a kidney biopsy, which revealed anti-glomerular basement membrane disease with underlying membranous nephropathy. He was treated with emergent hemodialysis, intravenous corticosteroids, plasmapheresis, and cyclophosphamide without improvement in his renal function. Conclusion Simultaneous anti-glomerular basement membrane disease and membranous nephropathy is very rare. There have been 16 previous case reports in the English language literature that have been associated with a high mortality and morbidity, and a very high rate of renal failure resulting in hemodialysis. Co-existence of membranous nephropathy and anti-glomerular basement membrane disease may be immune-mediated, although the exact mechanism is not clear.

  17. Multilayer moisture barrier

    Science.gov (United States)

    Pankow, Joel W; Jorgensen, Gary J; Terwilliger, Kent M; Glick, Stephen H; Isomaki, Nora; Harkonen, Kari; Turkulainen, Tommy

    2015-04-21

    A moisture barrier, device or product having a moisture barrier or a method of fabricating a moisture barrier having at least a polymer layer, and interfacial layer, and a barrier layer. The polymer layer may be fabricated from any suitable polymer including, but not limited to, fluoropolymers such as polyethylene terephthalate (PET) or polyethylene naphthalate (PEN), or ethylene-tetrafluoroethylene (ETFE). The interfacial layer may be formed by atomic layer deposition (ALD). In embodiments featuring an ALD interfacial layer, the deposited interfacial substance may be, but is not limited to, Al.sub.2O.sub.3, AlSiO.sub.x, TiO.sub.2, and an Al.sub.2O.sub.3/TiO.sub.2 laminate. The barrier layer associated with the interfacial layer may be deposited by plasma enhanced chemical vapor deposition (PECVD). The barrier layer may be a SiO.sub.xN.sub.y film.

  18. Thermal barriers for compartments

    Science.gov (United States)

    Kreutzer, Cory J.; Lustbader, Jason A.

    2017-10-17

    An aspect of the present disclosure is a thermal barrier that includes a core layer having a first surface, a second surface, and a first edge, and a first outer layer that includes a third surface and a second edge, where the third surface substantially contacts the first surface, the core layer is configured to minimize conductive heat transfer through the barrier, and the first outer layer is configured to maximize reflection of light away from the barrier.

  19. Tunnel barrier schottky

    Energy Technology Data Exchange (ETDEWEB)

    Chu, Rongming; Cao, Yu; Li, Zijian; Williams, Adam J.

    2018-02-20

    A diode includes: a semiconductor substrate; a cathode metal layer contacting a bottom of the substrate; a semiconductor drift layer on the substrate; a graded aluminum gallium nitride (AlGaN) semiconductor barrier layer on the drift layer and having a larger bandgap than the drift layer, the barrier layer having a top surface and a bottom surface between the drift layer and the top surface, the barrier layer having an increasing aluminum composition from the bottom surface to the top surface; and an anode metal layer directly contacting the top surface of the barrier layer.

  20. [Glomerular lipidosis].

    Science.gov (United States)

    Feriozzi, Sandro

    Lipidoses occur for an abnormal storage parenchymal deposition of lipids and products of their metabolism in large amounts or sometimes, involving only some particular tissue structures. The lipid storage is usually due to an inborn error causing an enzyme absence /deficiency in the primary lipidoses and to a complex metabolism alterations in the secondary forms. However, histologically all lipid depositions look very similar, and immunohistochemical investigation, clinical pictures knowledge and genetic tests need to make a correct diagnosis. Lipid deposition causes parenchymal structural changes especially of glomeruli resulting in renal function impairment and proteinuria and haematuria appearance. This manuscript gathers clinical and histological features present in these storage pathologies. Renal involvement is described in Anderson-Fabry disease, in hyperlipoproteinemias, in lecithin-cholesterol acyltransferase deficiency, in Gaucher disease and finally in secondary lipidoses features such as nephrotic syndrome, Alagille disease, and toxic or ischemic renal damage. Recently the replacement enzymatic therapy availability is substantially modifying the clinical picture and the outcome in some lipidoses such as Anderson-Fabry and Gaucher diseases. Therefore, it is import to be aware of these disorders, not only for making a correct diagnosis but also for starting, when it is possible, an effective therapy.

  1. The associations of Bmi-1 with progression of glomerular chronic kidney disease
.

    Science.gov (United States)

    Yang, Xiaoxia; Bai, Ming; Ning, Xiaoxuan; Ma, Feng; Liu, Limin; Liu, Ting; Liu, Minna; Wang, Hanmin; Sun, Shiren

    2018-02-01

    Our previous studies indicated that Bmi-1 plays an important role in hypoxia-induced tubular epithelial-mesenchymal transition and the development of kidney fibrosis in cellular and animal models. However, circulating Bmi-1 levels in human chronic kidney disease (CKD) and their relation to progression remains unknown. We conducted a post-hoc analysis of a prospective cohort study. The blood samples and clinical data of 230 patients with glomerular CKD and 67 healthy adults were prospectively collected between January 2010 and June 2012. Serum Bmi-1 was measured using enzyme-linked immunosorbent assay (ELISA). CKD patients had significantly higher serum Bmi-1 concentrations than the healthy controls (496.4 (363.1 - 675.4) pg/mL compared with 257.3 (235.4 - 303.8) pg/mL, p Bmi-1 level inversely correlated with the estimated glomerular filtration rate (eGFR) (r = -0.346, p Bmi-1 levels and serum creatinine, blood urea nitrogen, cystatin C concentration, and the severity of tubulointerstitial fibrosis (r = 0.248, p Bmi-1 level was associated with a shorter duration of renal survival. Cox multivariate analyses further demonstrated that serum Bmi-1 concentration was an independent prognostic factor for CKD patients (HR = 6.48, p Bmi-1 levels were associated with adverse kidney disease outcome, suggesting that Bmi-1 is a novel biomarker for glomerular CKD progression. More data from larger longitudinal studies are required to validate our findings.
.

  2. Evaluation of renal glomerular and tubular functional and structural integrity in neonates.

    Science.gov (United States)

    Awad, Hesham; el-Safty, Ibrahim; el-Barbary, Mohamed; Imam, Safaa

    2002-11-01

    Renal cells are not fully differentiated at birth, representing a major risk in preterm infants. We evaluated glomerular and tubular functional integrity as well as structural integrity of renal tubules among healthy full-term and preterm infants as well as diseased preterm infants. A total of 50 newborns (10 healthy full-term, 10 healthy preterm, and 30 diseased preterm, at 38.9 +/- 1.10, 34.2 +/- 0.92, and 32 +/- 2.47 weeks gestational age, respectively) were included in the present study. Glomerular function was assessed by measuring urinary levels of both microalbumin and immunoglobulin G as well as serum creatinine levels, whereas the proximal tubular function was investigated by measuring the urinary levels of both alpha1-microglobulin and beta2-microglobulin as well as retinol-binding protein. Also, distal tubular reabsorption capacity was investigated by assessing fractional excretion of sodium. Moreover, the structural integrity of renal proximal tubules was studied by measuring the urinary activities of both the brush-border membrane enzyme leucine-aminopeptidase (LAP) and the lysosomal enzyme N-acetyl-beta-D-glucosaminidase. The preceding investigations were done on both the first and third days of life of all 50 newborns. Glomerular and tubular function and structure was relatively impaired at birth among both healthy and diseased preterm as well as healthy full-term neonates and improved rapidly thereafter. The diseased preterm neonates showed worse renal function and structure with minimal improvement regardless of the underlying sickness. Renal insufficiency and renal immaturity could be evaluated using enzymuria and low- and high-molecular-weight proteinuria as noninvasive methods.

  3. Glomerular diseases in a Hispanic population: review of a regional renal biopsy database

    Directory of Open Access Journals (Sweden)

    Luis Fernando Arias

    Full Text Available CONTEXT AND OBJECTIVE: Epidemiological data provide useful information for clinical practice and investigations. This study aimed to determine glomerular disease frequencies in a region of Colombia and it represents the basis for future studies. DESIGN AND SETTING: Single-center retrospective analysis at the University of Antioquia, Colombia. METHODS: All native renal biopsies (July 1998 to December 2007 were reviewed, but only glomerular diseases were analyzed. The diagnosis of each case was based on histological, immunopathological and clinical features. RESULTS: A total of 1,040 biopsies were included. In 302 cases (29.0%, the patient's age was < 15 years. Primary glomerular diseases were diagnosed in 828 biopsies (79.6% and secondary in 212 (20.4%. The most common primary diseases were focal and segmental glomerulosclerosis (FSGS (34.8%, immunoglobulin A (IgA nephropathy (IgAN (11.8%, membranous glomerulonephritis (MGN (10.6%, minimal change disease (MCD (10.6%, crescentic glomerulonephritis (GN (5.6%, and non-IgA mesangial proliferative GN (5.6%. Postinfectious GN represented 10.7% of the diagnoses if included as primary GN. Lupus nephritis corresponded to 17.8% of the entire series. In adults, the order of the most frequent primary diseases was: FSGS, IgAN, MGN, crescentic GN and MCD. In children (< 15 years, the most frequent were: FSGS, postinfectious GN, MCD, non-IgA mesangial proliferative GN, endocapillary diffuse GN and IgAN. CONCLUSIONS: As among Afro-Americans, FSGS is the most frequent type of glomerulopathy in our population, but in our group, there are more cases of IgAN. The reasons for these findings are unclear. This information is an important contribution towards understanding the prevalence of renal diseases in Latin America.

  4. Hydroxyurea treatment decreases glomerular hyperfiltration in children with sickle cell anemia.

    Science.gov (United States)

    Aygun, Banu; Mortier, Nicole A; Smeltzer, Matthew P; Shulkin, Barry L; Hankins, Jane S; Ware, Russell E

    2013-02-01

    Glomerular hyperfiltration and microalbuminuria/proteinuria are early manifestations of sickle nephropathy. The effects of hydroxyurea therapy on these renal manifestations of sickle cell anemia (SCA) are not well defined. Our objective was to investigate the effects of hydroxyurea on glomerular filtration rate (GFR) measured by (99m)Tc-DTPA clearance, and on microalbuminuria/proteinuria in children with SCA. Hydroxyurea study of long-term effects (HUSTLE) is a prospective study (NCT00305175) with the goal of describing the long-term cellular, molecular, and clinical effects of hydroxyurea therapy in SCA. Glomerular filtration rate, urine microalbumin, and serum cystatin C were measured before initiating hydroxyurea therapy and then repeated after 3 years. Baseline and Year 3 values for HUSTLE subjects were compared using the Wilcoxon Signed Rank test. Associations between continuous variables were evaluated using Spearman correlation coefficient. Twenty-three children with SCA (median age 7.5 years, range, 2.5-14.0 years) received hydroxyurea at maximum tolerated dose (MTD, 24.4 ± 4.5 mg/kg/day, range, 15.3-30.6 mg/kg/day). After 3 years of treatment, GFR measured by (99m)Tc-DTPA decreased significantly from 167 ± 46 mL/min/1.73 m² to 145 ± 27 mL/min/1.73 m² (P = 0.016). This decrease in GFR was significantly associated with increase in fetal hemoglobin (P = 0.042) and decrease in lactate dehydrogenase levels (P = 0.035). Urine microalbumin and cystatin C levels did not change significantly. Hydroxyurea at MTD is associated with a decrease in hyperfiltration in young children with SCA. Copyright © 2012 Wiley Periodicals, Inc.

  5. The glomerular parietal epithelial cell's responses are influenced by SM22 alpha levels.

    Science.gov (United States)

    Naito, Shokichi; Pippin, Jeffrey W; Shankland, Stuart J

    2014-11-06

    Studies have shown in several diseases initially affecting podocytes, that the neighboring glomerular parietal epithelial cells (PECs) are secondarily involved. The PEC response might be reparative under certain circumstances, yet injurious under others. The factors governing these are not well understood. We have shown that SM22α, an actin-binding protein considered a marker of smooth muscle differentiation, is upregulated in podocytes and PECs in several models of podocyte disease. However, the impact of SM22α levels on PECs is not known. Experimental glomerular disease, characterized by primary podocyte injury, was induced in aged-matched SM22α+/+ and SM22α-/-mice by intraperitoneal injection of sheep anti-rabbit glomeruli antibody. Immunostaining methods were employed on days 7 and 14 of disease. The number of PEC transition cells, defined as cells co-expressing a PEC protein (PAX2) and podocyte protein (Synaptopodin) was higher in diseased SM22α-/-mice compared with SM22α+/+mice. WT1 staining along Bowman's capsule is higher in diseased SM22α-/-mice. This was accompanied by increased PEC proliferation (measured by ki-67 staining), and an increase in immunostaining for the progenitor marker NCAM, in a subpopulation of PECs in diseased SM22α-/-mice. In addition, immunostaining for vimentin and alpha smooth muscle actin, markers of epithelial-to-mesenchymal transition (EMT), was lower in diseased SM22α-/-mice compared to diseased SM22α+/+mice. SM22α levels may impact how PECs respond following a primary podocyte injury in experimental glomerular disease. Absent/lower levels favor an increase in PEC transition cells and PECs expressing a progenitor marker, and a lower EMT rate compared to SM22α+/+mice, where SM22 levels are markedly increased in PECs.

  6. Changes in glomerular parietal epithelial cells in mouse kidneys with advanced age.

    Science.gov (United States)

    Roeder, Sebastian S; Stefanska, Ania; Eng, Diana G; Kaverina, Natalya; Sunseri, Maria W; McNicholas, Bairbre A; Rabinovitch, Peter; Engel, Felix B; Daniel, Christoph; Amann, Kerstin; Lichtnekert, Julia; Pippin, Jeffrey W; Shankland, Stuart J

    2015-07-15

    Kidney aging is accompanied by characteristic changes in the glomerulus, but little is known about the effect of aging on glomerular parietal epithelial cells (PECs), nor if the characteristic glomerular changes in humans and rats also occur in very old mice. Accordingly, a descriptive analysis was undertaken in 27-mo-old C57B6 mice, considered advanced age. PEC density was significantly lower in older mice compared with young mice (aged 3 mo), and the decrease was more pronounced in juxtamedullary glomeruli compared with outer cortical glomeruli. In addition to segmental and global glomerulosclerosis in older mice, staining for matrix proteins collagen type IV and heparan sulfate proteoglycan were markedly increased in Bowman's capsules of older mouse glomeruli, consistent with increased extracellular matrix production by PECs. De novo staining for CD44, a marker of activated and profibrotic PECs, was significantly increased in aged glomeruli. CD44 staining was more pronounced in the juxtamedullary region and colocalized with phosphorylated ERK. Additionally, a subset of aged PECs de novo expressed the epithelial-to-mesenchymal transition markers α-smooth muscle and vimentin, with no changes in epithelial-to-mesenchymal transition markers E-cadherin and β-catenin. The mural cell markers neural/glial antigen 2, PDGF receptor-β, and CD146 as well as Notch 3 were also substantially increased in aged PECs. These data show that mice can be used to better understand the aging kidney and that PECs undergo substantial changes, especially in juxtamedullary glomeruli, that may participate in the overall decline in glomerular structure and function with advancing age. Copyright © 2015 the American Physiological Society.

  7. Transforming Education: Overcoming Barriers.

    Science.gov (United States)

    David, Jane L.; Goren, Paul D.

    Barriers to progress in educational reform exist inside and outside the education system. Some arise where new practices encounter traditional expectations and boundaries, but others go much deeper than education, such as poverty, racism, local political conflicts, and human resistance to change. The following five categories of barriers are…

  8. Computation of glomerular filtration rate with Tc-99m DTPA: an in-house computer program

    International Nuclear Information System (INIS)

    Gates, G.F.

    1984-01-01

    The glomerular filtration rate (GFR) can be computed from the scintigraphic determination of Tc-99m DTPA (diethylenetriaminepentaacetic acid) uptake within the kidneys. The required computations are straightforward and can easily be included in the software of various computers, including a hospital's existing data-processing system. This report present a complete operational program based on extensive experience with this method. The program is easy to use, allows for adjustments to be made for unusual clinical conditions, and produces a permanent record that can be issued as part of the final report

  9. Glomerular filtration rate in transplantation patients: estimation of renal function using Tc-99m DTPA

    International Nuclear Information System (INIS)

    Reinig, J.W.; Gordon, L.; Frey, D.; Garrick, E.; Daniel, W.T. III

    1985-01-01

    The clinical assessment of a transplanted kidney is often difficult, especially in the immediate postoperative period. The biochemical parameters used to monitor renal function change slowly and can take several days to reflect the actual renal status. The authors have modified a technique for determining the glomerular filtration rate (GFR) from a Tc-99m DTPA renal scan and have found that it correlates with the actual GFR throughout the postoperative course. In addition, they describe a method for changing dose calibrator measurements into administered counts. This technique for determining the GFR provides a quick and accurate assessment of renal function and is useful to guide therapeutic decisions

  10. Glomerular filtration rate in children: determination from the Tc-99m-DTPA renogram

    International Nuclear Information System (INIS)

    Shore, R.M.; Koff, S.A.; Mentser, M.; Hayes, J.R.; Smith, S.P.; Smith, J.P.; Chesney, R.W.

    1984-01-01

    Analysis of the Tc-99m-DTPA renogram is usually limited to calculating the relative function of each kidney. To develop a method to determine the absolute glomerular filtration rate (GFR), various methods of analyzing the renogram were examined to determine which gave the best correlation with GFR. That regression could then be used to predict GFR without the need for blood samples. Fifty children were studied using Tc-99m-DPTA renograms and GFR measured simultaneously by plasma disappearance. GFR correlated better with the slope of the second phase than with the area under the renogram curve. This method can accurately estimate GFR from the renogram in children

  11. Measurement of glomerular filtration in dogs by 51Cr-EDTA and 113In-DTPA

    International Nuclear Information System (INIS)

    Maliska, C.; Saraiva, J.C.G.

    1977-01-01

    The glomerular filtration rate (GFR) was measured in 15 normal dogs using 51 Cr-EDTA and 113 sup(m) In-DTPA, by a single injection technique. The results of GFR measurements was 3,01 (S.D. + - 0,71) ml/min/kg body weight, and 70,44 (S.D. + - 19,60) ml/min/m 2 surface area. Difference in GFR (means) between the measurement by 51 Cr-EDTA and 113 sup(m) In-DTPA and between the male and female group was not statistically significant (p [pt

  12. Tubulo-glomerular feedback response: enhancement in adult spontaneously hypertensive rats and effects of anaesthetics

    DEFF Research Database (Denmark)

    Leyssac, P P; Holstein-Rathlou, N H

    1989-01-01

    ) and stop-flow pressures (40.0-42.4 mm Hg) were similar in the four groups, but systemic arterial pressure was significantly lower in WKY, and significantly higher in SHR than in SPRD. The turning point (Tp) of the feedback curve was 9.87 nl/min in SHR, significantly lower than the 13.04 nl/min found in WKY......Open-loop tubulo-glomerular feedback (TGF) responses were measured in halothane anaesthetized spontaneously hypertensive rats (SHR), in normotensive Wistar Kyoto (WKY) and Sprague-Dawley rats (SPRD), and in inactin anaesthetized SPRD. Proximal intratubular free flow pressures (FFP) (13.8-14.7 mm Hg...

  13. Glomerular filtration rate in children with advanced chronic renal failure: methods of determination and clinical applications.

    Science.gov (United States)

    Chan, J C; Sharpe, A R

    1982-01-01

    The rationale, significance and pitfalls of currently available methods for the determination of glomerular filtration rates in children with advanced chronic renal diseases are reviewed. Normal renal clearances in infants and children from birth to adulthood are presented. Methods of serial measurements of renal function, especially by the reciprocals of serum creatinine concentrations, are evaluated. They are applied clinically to monitor the effectiveness of conservative and new modalities of treatment, such as dietary supplementation with essential amino acids plus their keto analogues, and to determine that 1,25-dihydroxyvitamin-D3 treatment of renal osteodystrophy does not accelerate the deterioration of renal function in children with chronic renal insufficiency.

  14. Measurement of glomerular filtration rate in children using technetium-99m diethylenetriamine penta-acetic acid

    International Nuclear Information System (INIS)

    Aaronson, I.A.; Mann, M.D.

    1985-01-01

    During the past 5 years, we have measured the glomerular filtration rate (GFR) by the slope-clearance method using technetium-99m diethylenetriamine penta-acetic acid technetium-99m-DTPA in 130 infants and children. The results in 22 children have been compared with inulin clearance, and a very good correlation between the two methods of measurement of GFR was demonstrated (r = 0,9616; P less than 0,0001). This study provides further evidence that technetium-99m-DTPA is a satisfactory agent for the clinical measurement of GFR in children

  15. Comparative evaluation of iohexol and inulin clearance for glomerular filtration rate determinations

    International Nuclear Information System (INIS)

    Lindblad, H.G.; Berg, U.B.

    1994-01-01

    The authors have evaluated iohexol as a filtration marker in 150 children. The clearance of iohexol was compared with that of inulin or with a formula clearance. The single-sample clearance of iohexol showed a good correlation with the clearance of inulin. The clearance of iohexol correlated well with the formula clearance. The optimal blood sampling time for iohexol clearance determinations appears to be between 120 and 180 min after injection, at least in patient with relatively normal filtration rates. It is concluded that iohexol clearance is an accurate method of determining the glomerular filtration rate in clinical practice. 25 refs., 5 figs

  16. Anti-glomerular basement membrane: A rare cause of renal failure in children

    Directory of Open Access Journals (Sweden)

    Indira Agarwal

    2017-01-01

    Full Text Available Anti-glomerular basement membrane (GBM disease is a rare cause of acute renal failure and known to have bad prognosis regarding renal functions recovery and patient survival specially when diagnosed late and presents with severe renal failure that requires dialysis. We report a case of 11-year-old child with acute renal failure secondary to anti-GBM disease and associated with antineutrophil cytoplasmic antibody-positive vasculitis. He was treated with plasmapheresis, steroids, and cyclophosphamide with recovery of his kidney functions.

  17. Rapid decline in glomerular filtration rate during the first weeks following heart transplantation

    DEFF Research Database (Denmark)

    Hornum, M; Andersen, M; Gustafsson, F

    2011-01-01

    We hypothesized that a decrease in renal function is seen immediately after heart transplantation (HTX) with little recovery over time. Twelve consecutive patients had their glomerular filtration rate (GFR) measured using (51)Cr-ethylenediaminetetraacetic acid (EDTA) measured GFR (mGFR) before...... transplantation and at 1, 2, 3, and 26 weeks after transplantation. The mGFR decreased by 28% and 24% during the first 3 and 26 weeks, respectively, with mean blood cyclosporine concentration as an independent risk factor for the decrease in mGFR. The identification of cyclosporine A (CsA) as the most important...

  18. Tubular and glomerular injury in diabetes and the impact of ACE inhibition

    DEFF Research Database (Denmark)

    Nielsen, Stine E; Sugaya, Takeshi; Tarnow, Lise

    2009-01-01

    OBJECTIVE: We studied tubular and glomerular damage in type 1 diabetic patients by measuring urinary-liver fatty acid binding protein (U-LFABP) and albuminuria. Subsequently, we evaluated the effect of ACE inhibition on U-LFABP in patients with diabetic nephropathy. RESEARCH DESIGN AND METHODS: We......, 46, and 40% with increasing doses of lisinopril (NS). CONCLUSIONS: An early and progressive increase in tubulointerstitial damage as reflected by increased U-LFABP levels occurs in type 1 diabetic patients and is associated with albuminuria. Furthermore, ACE inhibition reduces the tubular...

  19. Novel therapeutic approaches for chronic kidney disease due to glomerular disorders.

    Science.gov (United States)

    Del Nogal-Avila, Maria; Donoro-Blazquez, Hector; Saha, Manish K; Marshall, Caroline B; Clement, Lionel C; Macé, Camille E A; Chugh, Sumant S

    2016-07-01

    Improved understanding of glomerular disease mechanisms over the past decade has led to the emergence of new and targeted therapeutic strategies for chronic kidney disease (CKD). Most promising among these are the administration of recombinant mutated human angiopoietin-like 4, sialic acid-related sugars that induce sialylation in vivo, compounds related to Bis-T-23, and immune depletion of the soluble urokinase receptor from the circulation. Taking these therapeutic strategies into clinical trials will be the first step away from repurposed and relatively toxic drugs currently used for treating kidney disease. Copyright © 2016 the American Physiological Society.

  20. TLR4 links podocytes with the innate immune system to mediate glomerular injury

    DEFF Research Database (Denmark)

    Banas, Miriam C; Banas, Bernhard; Hudkins, Kelly L

    2008-01-01

    profile of chemokines. In conclusion, it was demonstrated that TLR4 is constitutively expressed by podocytes and is upregulated in MPGN, where it may mediate glomerular injury by modulating expression of chemokines; therefore, TLR4 may link podocytes with the innate immune system to mediate MPGN triggered......Toll-like receptors (TLR) classically recognize pathogen-associated danger signals but are also activated via endogenous ligands. For evaluation of their role in inflammatory kidney disease, the function of TLR was analyzed in two mouse models of cryoglobulinemic membranoproliferative...... by the deposition of immune complexes....

  1. Catalytic thermal barrier coatings

    Science.gov (United States)

    Kulkarni, Anand A.; Campbell, Christian X.; Subramanian, Ramesh

    2009-06-02

    A catalyst element (30) for high temperature applications such as a gas turbine engine. The catalyst element includes a metal substrate such as a tube (32) having a layer of ceramic thermal barrier coating material (34) disposed on the substrate for thermally insulating the metal substrate from a high temperature fuel/air mixture. The ceramic thermal barrier coating material is formed of a crystal structure populated with base elements but with selected sites of the crystal structure being populated by substitute ions selected to allow the ceramic thermal barrier coating material to catalytically react the fuel-air mixture at a higher rate than would the base compound without the ionic substitutions. Precious metal crystallites may be disposed within the crystal structure to allow the ceramic thermal barrier coating material to catalytically react the fuel-air mixture at a lower light-off temperature than would the ceramic thermal barrier coating material without the precious metal crystallites.

  2. Urological disorders in chronic kidney disease in children cohort: clinical characteristics and estimation of glomerular filtration rate.

    Science.gov (United States)

    Dodson, Jennifer L; Jerry-Fluker, Judith V; Ng, Derek K; Moxey-Mims, Marva; Schwartz, George J; Dharnidharka, Vikas R; Warady, Bradley A; Furth, Susan L

    2011-10-01

    Urological disorders are the most common cause of pediatric chronic kidney disease. We determined the characteristics of children with urological disorders and assessed the agreement between the newly developed bedside glomerular filtration rate estimating formula with measured glomerular filtration rate in 586 patients in the Chronic Kidney Disease in Children study. The Chronic Kidney Disease in Children study is a prospective, observational cohort of children recruited from 48 sites in the United States and Canada. Eligibility requirements include age 1 to 16 years and estimated glomerular filtration rate by original Schwartz formula 30 to 90 ml/min/1.73 m(2). Baseline demographics, clinical variables and glomerular filtration rate were assessed. Bland-Altman analysis was conducted to assess agreement between estimated and measured glomerular filtration rates. Of the 586 participants with at least 1 glomerular filtration rate measurement 348 (59%) had an underlying urological diagnosis (obstructive uropathy in 118, aplastic/hypoplastic/dysplastic kidneys in 104, reflux in 87 and other condition in 39). Among these patients median age was 9 years, duration of chronic kidney disease was 7 years and age at first visit with a urologist was less than 1 year. Of the patients 67% were male, 67% were white and 21% had a low birth weight. Median height was in the 24th percentile. Median glomerular filtration rate as measured by iohexol plasma disappearance was 44.8 ml/min/1.73 m(2). Median glomerular filtration rate as estimated by the Chronic Kidney Disease in Children bedside equation was 44.3 ml/min/1.73 m(2) (bias = -0.5, 95% CI -1.7 to 0.7, p = 0.44). Underlying urological causes of chronic kidney disease were present in 59% of study participants. These children were diagnosed early in life, and many had low birth weight and growth delay. There is good agreement between the newly developed Chronic Kidney Disease in Children estimating equations and measured

  3. Underlying renal insufficiency: the pivotal risk factor for Pneumocystis jirovecii pneumonia in immunosuppressed patients with non-transplant glomerular disease.

    Science.gov (United States)

    Ye, Wen-Ling; Tang, Nan; Wen, Yu-Bing; Li, Hang; Li, Min-Xi; Du, Bin; Li, Xue-Mei

    2016-11-01

    Data on PCP in patients with glomerular disease are rare. The aim of this study was to assess the predictors of PCP development, the risk factors for mortality and the incidence of acute kidney injury (AKI) when high-dose trimethoprim-sulphamethoxazole (TMP-SMX) was used in patients with non-transplant glomerular disease. Forty-seven patients with PCP, as confirmed by positive results for Pneumocystis jirovecii DNA or Pneumocystis jirovecii cysts tested by a methenamine silver stain between January 1, 2003, and December 30, 2012, were retrospectively investigated. The baseline characteristics of glomerular disease, clinical findings of PCP and renal parameters after treatment were collected. Predictors for PCP development and risk factors for mortality were determined using a multivariate logistic regression analysis. All PCP patients exclusively received immunosuppressants. Baseline renal insufficiency [estimated glomerular filtration rate (eGFR) renal function to baseline values. PCP is a fatal complication in patients with glomerular disease, and the use of immunosuppressants may be a basic risk factor for this infection. Underlying renal insufficiency and high renal pathology chronicity are the key risk factors for PCP in IgA nephropathy. TMP-SMX therapy remains an ideal choice because of high treatment response and frequently reversible kidney injury.

  4. Glomerular filtration rate by {sup 51}chomium and {sup 113m}indium labeled EDTA in horses; Taxa de filtracao glomerular pelo EDTA marcado com {sup 51}cromo e com {sup 113m}indio em equinos

    Energy Technology Data Exchange (ETDEWEB)

    Maliska, C.; D' Almeida, J.; Pellegrini, P.M.; Schimit, T.S. [Hospital Central do Exercito (HCE), Rio de Janeiro, RJ (Brazil). Servico de Medicina Nuclear; Pinho, W.R. [Centro de Ensino Superior, Valenca, RJ (Brazil). Fac. de Medicina Veterinaria; Lima, J.E.T. [Instituto Nacional do Cancer (INCa), Rio de Janeiro, RJ (Brazil). Servico de Medicina Nuclear

    2009-07-01

    The glomerular filtration rate was determined in nine healthy horses, six male and three female, aged two to 12-year-old, by means of {sup 51}Cr and {sup 113m}In labeled EDTA single injection technique. The glomerular filtration rate was calculated from the plasma disappearance curve and the volume of distribution of the radiotracer, {sup 51}Cr-EDTA or {sup 113m}In-EDTA. The result (mean +- standard deviation) was 148.80 +- 26.42 m L.min{sup -1}.100 kg. It is concluded that the measurement of glomerular filtration rate by {sup 51}Cr-EDTA or {sup 113m}In-EDTA by single injection technique eliminates the bladder catheterization, and for its simplicity, convenience, accuracy, and low dose of radiation, can be used in horses as a method of choice in clinical routine. (author)

  5. Glomerulonefritis fibrilar: Una rara forma de enfermedad glomerular por depósitos organizados Fibrillary glomerulo-nephritis: A rare form of glomerular disease with organized deposits

    Directory of Open Access Journals (Sweden)

    Marta B. Cabrera

    2011-10-01

    Full Text Available Se describe el caso de una mujer de 67 años de edad que consultó por debilidad y astenia, constatándose proteinuria de rango nefrótico y dislipemia. Se realizó punción para biopsia renal, la que se analizó por microscopia óptica, inmunofluorescencia y microscopia electrónica de transmisión. El análisis ultra-estructural reveló la existencia de depósitos fibrilares organizados, rectos, no ramificados, cuyo espesor osciló entre 15 y 20 nm. Dichas fibrillas ópticamente se veían como una expansión mesangial discretamente nodular, ligeramente PAS positiva, rojo Congo negativa y débilmente positiva para IgG. El diagnóstico fue glomerulonefritis fibrilar. Las enfermedades glomerulares por depósitos organizados pueden exhibir superposición sindrómica e histopatológica. Por tal motivo, resulta de importancia una primera separación entre aquellas rojo Congo positivas o negativas, siendo en este último caso la microscopia electrónica de transmisión la que diferencia dos entidades: la glomerulonefritis fibrilar y la glomerulonefritis inmunotactoide. Esta diferencia se apoya no sólo en las características ultraestructurales, sino en sus características clínicas. La glomerulonefritis inmunotactoide muestra una fuerte asociación con procesos linfoproliferativos, a diferencia de lo que ocurre con la glomerulonefritis fibrilar.We describe the case of a 67 year-old female who presented weakness and fatigue. Laboratory data showed nephrotic level of proteinuria and dyslipidemia. A renal biopsy was performed, and studied by light microscopy, immuno-fluorescence and electron microscopy. Ultra-structural analysis revealed the existence of organized fibrillary deposits, straight and without ramifications, the thickness of which ranged from 15 to 20 nm. These fibres were identified, by light microscopy, as slightly nodular mesangial expansions PAS positive, Congo red negative and weakly positive for IgG. Given the above findings, the

  6. Vehicle barrier systems

    International Nuclear Information System (INIS)

    Sena, P.A.

    1986-01-01

    The ground vehicle is one of the most effective tools available to an adversary force. Vehicles can be used to penetrate many types of perimeter barriers, transport equipment and personnel rapidly over long distances, and deliver large amounts of explosives directly to facilities in suicide missions. The function of a vehicle barrier system is to detain or disable a defined threat vehicle at a selected distance from a protected facility. Numerous facilities are installing, or planning to install, vehicle barrier systems and many of these facilities are requesting guidance to do so adequately. Therefore, vehicle barriers are being evaluated to determine their stopping capabilities so that systems can be designed that are both balanced and capable of providing a desired degree of protection. Equally important, many of the considerations that should be taken into account when establishing a vehicle barrier system have been identified. These considerations which pertain to site preparation, barrier selection, system integration and operation, and vehicle/barrier interaction, are discussed in this paper

  7. Contrast media and glomerular filtration: dose dependence of clearance for three agents

    International Nuclear Information System (INIS)

    Baeck, S.E.K.; Krutzen, E.; Nilsson-Ehle, P.

    1988-01-01

    Determination of plasma clearance of contrast agents has been advocated as a means to assess glomerular filtration rate. To evaluate the feasibility of different agents for this purpose, we have compared, in healthy volunteers, the dose dependence of plasma clearance for three contrast media (iohexol, a nonionic agent, and iothalamate and metrizoate, which are ionic substances), with special emphasis on the lower dose range (2-20 mL corresponding to 0.9-12.9 g, depending on dose and agent). Iohexol and iothalamate were cleared at constant rates, irrespective of given dose, whereas metrizoate clearance increased significantly at lower doses. In general, the clearances or iothalamate and metrizoate were, respectively, moderately and markedly higher than that of iohexol. The clearance of different doses of metrizoate (2 mL versus a radiographic dose of 40 mL or more) was also compared with the clearance of [ 51 Cr]EDTA in two groups of patients with reduced renal function. When compared with [ 51 Cr]EDTA in patients with renal dysfunction, metrizoate was cleared significantly faster after a 2-mL dose, whereas clearances were identical when the metrizoate dose was 40 mL or more. These findings indicate that tubular secretion plays an active role in the elimination of metrizoate. The pharmacokinetic properties of iohexol, in combination with its low toxicity, make it a suitable agent for determination of glomerular filtration rate in clinical practice

  8. Three-exponential method for determination of glomerular filtration rate by 169Yb-EDTA

    International Nuclear Information System (INIS)

    Kyuldzhiev, A.; Nikolova, I.; Vitanova, Zh.; Velikov, P.; Stavrev, P.

    1990-01-01

    The method is based on blood clearance curves obtained by external detection over the precordial area of 21 patients after single injection of 2.6 - 3.7 mBq 169 Yb-EDTA. The accuracy of curve preparation is obtained by big number of points measured every minute until the 20th min after injection, at 2 min interval until the 30th min and at 5 min interval until the 240th min. FUMILI microcomputer program (created in JINR, Dubna, and also used in CERN) was applied vor resolving the clearance curves into exponents. The three exponents received prompt to determine the glomerular filtration in a way taking into account the contribution of each of them. For this purpose the authors introduce a formula for calculating the 'efficient period of half-purification', which contain corrections for three-compartment model of distribution and deposition of the radiopharmaceutical. The glomerular filtration determined by this method in 23 patients has higher values compared to one-compartment models which take into account only the third, most slow exponent. 1 fig., 1 tab., 7 refs

  9. Radionuclide measurement of differential glomerular filtration rate in urinary tract obstruction

    International Nuclear Information System (INIS)

    Powers, T.A.; Stone, W.J.; Lowe, B.A.; Patton, J.A.; Bowen, R.D.

    1982-01-01

    In a previous study using dogs whose renal function was rendered asymmetric by unilateral infarction, the efficacy of technetium-99m (/sup 99m/Tc) DTPA and DMSA in measuring differential glomerular filtration rate (GFR) was demonstrated. The present study was undertaken to determine whether the same techniques were applicable to unilateral ureteral obstruction. Five normal dogs and nine dogs with partial unilateral ureteral obstruction had determination of glomerular filtration rate by standard techniques using constant infusions of iothalamate and creatinine after ureteral catheterization. These results were compared with total GFR as measured by single injection of /sup 99m/Tc DTPA and analysis of the plasma disappearance curve. Calculated differential GFR was obtained by multiplying total GFR from double exponential analysis of this curve (DTPA2) by each of three measures of differential function. These included the percent differential uptake of /sup 99m/Tc DTPA and /sup 99m/Tc DMSA in the posterior projection as well as the geometric mean of /sup 99m/Tc DMSA uptake. There were good correlations between differential GFR determined by iothalamate clearances at ureteral catheterization and all noninvasive methods involving radionuclides and DTPA2 ( r . 0.93-0.99). Single exponential analysis of the /sup 99m/Tc DTPA plasma disappearance curve was less satisfactory than double exponential analysis. These results and those reported previously support the use of radionuclides in the determination of differential GFR in a variety of clinical situations

  10. Clinico-pathological study of glomerular diseases in patients with significant proteinuria in North India

    Directory of Open Access Journals (Sweden)

    Irneet Mundi

    2014-01-01

    Full Text Available Proteinuria is a common manifestation of renal disease. The present study was carried out to analyze the clinic-pathological correlation, assess the value of histopathology and immunofluorescence (IF as well as note the spectrum of renal diseases in patients with significant proteinuria. Fifty consecutive patients having proteinuria >1 g/24 h underwent ultrasound-guided percutaneous renal biopsy. Clinical information was correlated with the pathological findings and the results were analyzed. The patients were in the age range of 12-79 years. Males (60% outnumbered females (40% in all the disease categories except lupus nephritis and IgA nephropathy. The most common clinical presentation was the nephrotic syndrome, seen in 31 cases (62%. Primary glomerular diseases (72% were more common than secondary glomerular diseases (24% and tubulointerstitial diseases (4%. Overall, the most common pathological diag-nosis was focal and segmental glomerulosclerosis (FSGS (20%, followed by membranous glomerulonephritis (MGN (18%. In young patients (age 60 years it was FSGS (60%. IF modified the diagnosis in 12% of the cases. The concordance between clinical diagnosis and pathological diagnosis was 66%. The difference between clinical diagnosis and final diagnosis was statistically significant. Our study further reinforces the knowledge that renal biopsy helps in accurate diagnosis and, thus, helps in appropriate management of the patients. IF provides additional information that can make the morphologic diagnosis considerably more precise.

  11. The Effect of Alium Satium Extract on the Glomerular Diameter of STZ -induced Sprague dawley Rats

    Directory of Open Access Journals (Sweden)

    Susilorini Susilorini

    2013-06-01

    Full Text Available Hyperglycemia exert toxic effect in kidney.The aim of this study was to investigate the short term effect of ethanolic extract of garlic in preventing nephropathy following streptozotocin (STZ induced rats. Twenty male Sprague dawley rats were randomly divided into 4 group, all group induced induced by single dose intraperitoneal injection of 40 mg kg-1 of streptozotocin (STZ. Treatment with 3 doses ethanolic extract of garlic (0,1; 0,25; 0,5 mg kg-1 day-1 was followed for 14 days, then the left kidneys were excised and histhopathological studies were carried out using scanner 3D Hitech and Panoramic view software. Statistical analysis have been done using non parametric analysis Kruskall Wallis. The study revealed that glomerular diameter of the treatment rats was significantly different from the control group (p=0,0001. Increasing doses didn’t make difference. The ethanolic extract of garlic (Allium sativum influences the diameter glomeruli but increasing doses has no effect on the glomerular diameter.

  12. A systematic review of glomerular hyperfiltration assessment and definition in the medical literature.

    Science.gov (United States)

    Cachat, Francois; Combescure, Christophe; Cauderay, Michel; Girardin, Eric; Chehade, Hassib

    2015-03-06

    Evaluation of glomerular hyperfiltration (GH) is difficult; the variable reported definitions impede comparisons between studies. A clear and universal definition of GH would help in comparing results of trials aimed at reducing GH. This study assessed how GH is measured and defined in the literature. Three databases (Embase, MEDLINE, CINAHL) were systematically searched using the terms "hyperfiltration" or "glomerular hyperfiltration". All studies reporting a GH threshold or studying the effect of a high GFR in a continuous manner against another outcome of interest were included. The literature search was performed from November 2012 to February 2013 and updated in August 2014. From 2013 retrieved studies, 405 studies were included. Threshold use to define GH was reported in 55.6% of studies. Of these, 88.4% used a single threshold and 11.6% used numerous thresholds adapted to participant sex or age. In 29.8% of the studies, the choice of a GH threshold was not based on a control group or literature references. After 2004, the use of GH threshold use increased (Psex-matched control group should be used to define a GH threshold. Copyright © 2015 by the American Society of Nephrology.

  13. Transcriptional profiling reveals progeroid Ercc1-/Δ mice as a model system for glomerular aging

    Science.gov (United States)

    2013-01-01

    Background Aging-related kidney diseases are a major health concern. Currently, models to study renal aging are lacking. Due to a reduced life-span progeroid models hold the promise to facilitate aging studies and allow examination of tissue-specific changes. Defects in genome maintenance in the Ercc1-/Δ progeroid mouse model result in premature aging and typical age-related pathologies. Here, we compared the glomerular transcriptome of young and aged Ercc1-deficient mice to young and aged WT mice in order to establish a novel model for research of aging-related kidney disease. Results In a principal component analysis, age and genotype emerged as first and second principal components. Hierarchical clustering of all 521 genes differentially regulated between young and old WT and young and old Ercc1-/Δ mice showed cluster formation between young WT and Ercc1-/Δ as well as old WT and Ercc1-/Δ samples. An unexpectedly high number of 77 genes were differentially regulated in both WT and Ercc1-/Δ mice (p aging glomerulus. At the level of the transcriptome, the pattern of gene activities is similar in the progeroid Ercc1-/Δ mouse model constituting a valuable tool for future studies of aging-associated glomerular pathologies. PMID:23947592

  14. Chronic Lyme borreliosis associated with minimal change glomerular disease: a case report.

    Science.gov (United States)

    Florens, N; Lemoine, S; Guebre-Egziabher, F; Valour, F; Kanitakis, J; Rabeyrin, M; Juillard, L

    2017-02-06

    There are only few cases of renal pathology induced by Lyme borreliosis in the literature, as this damage is rare and uncommon in humans. This patient is the first case of minimal change glomerular disease associated with chronic Lyme borreliosis. A 65-year-old Caucasian woman was admitted for an acute edematous syndrome related to a nephrotic syndrome. Clinical examination revealed violaceous skin lesions of the right calf and the gluteal region that occurred 2 years ago. Serological tests were positive for Lyme borreliosis and skin biopsy revealed lesions of chronic atrophic acrodermatitis. Renal biopsy showed minimal change glomerular disease. The skin lesions and the nephrotic syndrome resolved with a sequential treatment with first ceftriaxone and then corticosteroids. We report here the first case of minimal change disease associated with Lyme borreliosis. The pathogenesis of minimal change disease in the setting of Lyme disease is discussed but the association of Lyme and minimal change disease may imply a synergistic effect of phenotypic and bacterial factors. Regression of proteinuria after a sequential treatment with ceftriaxone and corticosteroids seems to strengthen this conceivable association.

  15. Automatic Reporting of Creatinine-Based Estimated Glomerular Filtration Rate in Children: Is this Feasible?

    Directory of Open Access Journals (Sweden)

    Andrew Lunn

    2016-07-01

    Full Text Available Creatinine, although widely used as a biomarker to measure renal function, has long been known as an insensitive marker of renal impairment. Patients with reduced renal function can have a creatinine level within the normal range, with a rapid rise when renal function is significantly reduced. As of 1976, the correlation between height, the reciprocal of creatinine, and measured glomerular filtration rate (GFR in children has been described. It has been used to derive a simple formula for estimated glomerular filtration rate (eGFR that could be used at the bedside as a more sensitive method of identifying children with renal impairment. Formulae based on this association, with modifications over time as creatinine assay methods have changed, are still widely used clinically at the bedside and in research studies to assess the degree of renal impairment in children. Adult practice has moved in many countries to computer-generated results that report eGFR alongside creatinine results using more complex, but potentially more accurate estimates of GFR, which are independent of height. This permits early identification of patients with chronic kidney disease. This review assesses the feasibility of automated reporting of eGFR and the advantages and disadvantages of this in children.

  16. Compound effects of aging and experimental FSGS on glomerular epithelial cells.

    Science.gov (United States)

    Schneider, Remington R S; Eng, Diana G; Kutz, J Nathan; Sweetwyne, Mariya T; Pippin, Jeffrey W; Shankland, Stuart J

    2017-02-17

    Advanced age portends a poorer prognosis in FSGS. To understand the impact of age on glomerular podocytes and parietal epithelial cells (PECs), experimental FSGS was induced in 3m-old mice (20-year old human age) and 27m-old mice (78-year old human age) by abruptly depleting podocytes with a cytopathic anti-podocyte antibody. Despite similar binding of the disease-inducing antibody, podocyte density was lower in aged FSGS mice compared to young FSGS mice. Activated PEC density was higher in aged versus young FSGS mice, as was the percentage of total activated PECs. Additionally, the percentage of glomeruli containing PECs with evidence of phosphorylated ERK and EMT was higher in aged FSGS mice. Extracellular matrix, measured by collagen IV and silver staining, was higher in aged FSGS mice along Bowman's capsule. However, collagen IV accumulation in the glomerular tufts alone and in glomeruli with both tuft and Bowman's capsule accumulation were similar in young FSGS and aged FSGS mice. Thus, the major difference in collagen IV staining in FSGS was along Bowman's capsule in aged mice. The significant differences in podocytes, PECs and extracellular matrix accumulation between young mice and old mice with FSGS might explain the differences in outcomes in FSGS based on age.

  17. Glomerular parietal epithelial cells contribute to adult podocyte regeneration in experimental focal segmental glomerulosclerosis.

    Science.gov (United States)

    Eng, Diana G; Sunseri, Maria W; Kaverina, Natalya V; Roeder, Sebastian S; Pippin, Jeffrey W; Shankland, Stuart J

    2015-11-01

    As adult podocytes cannot adequately proliferate following depletion in disease states, there has been interest in the potential role of progenitors in podocyte repair and regeneration. To determine whether parietal epithelial cells (PECs) can serve as adult podocyte progenitors following disease-induced podocyte depletion, PECs were permanently labeled in adult PEC-rtTA/LC1/R26 reporter mice. In normal mice, labeled PECs were confined to Bowman's capsule, whereas in disease (cytotoxic sheep anti-podocyte antibody) labeled PECs were found in the glomerular tuft in progressively higher numbers by days 7, 14, and 28. Early in disease, the majority of PECs in the tuft coexpressed CD44. By day 28, when podocyte numbers were significantly higher and disease severity was significantly lower, the majority of labeled PECs coexpressed podocyte proteins but not CD44. Neither labeled PECs on the tuft nor podocytes stained for the proliferation marker BrdU. The de novo expression of phospho-ERK colocalized to CD44 expressing PECs, but not to PECs expressing podocyte markers. Thus, in a mouse model of focal segmental glomerulosclerosis typified by abrupt podocyte depletion followed by regeneration, PECs undergo two phenotypic changes once they migrate to the glomerular tuft. Initially these cells are predominantly activated CD44 expressing cells coinciding with glomerulosclerosis, and later they predominantly exhibit a podocyte phenotype, which is likely reparative.

  18. Focal glomerular immune complex deposition: possible role of periglomerular fibrosis/atubular glomeruli.

    Science.gov (United States)

    Satoskar, Anjali A; Calomeni, Edward; Bott, Cherri; Nadasdy, Gyongyi M; Nadasdy, Tibor

    2009-02-01

    Consensus exists among renal pathologists that, in biopsies with immune complex glomerulonephritis, even a single glomerulus with open capillary loops may be sufficient for immunofluorescence and/or electron microscopy evaluation because immune complex deposition is a diffuse phenomenon. However, we have encountered renal biopsies with focal absence of immune complexes in glomeruli on either immunofluorescence or electron microscopy examination despite presence of open glomerular capillary loops. To evaluate renal biopsies with focal immune complex deposition and look for any subtle or unusual morphologic changes in the glomeruli (and in the biopsy in general). Native and transplant renal biopsies were reviewed. All biopsies had been triaged and processed according to our routine protocol for light microscopy, immunofluorescence, and electron microscopy examination. Of 2018 renal biopsies from December 2005 to December 2007, we found 10 such biopsies; 5 native and 5 transplant kidney biopsies. We found that the glomeruli with absent immune complex deposits had periglomerular fibrosis with open, albeit, wrinkled appearing capillary loops but no glomerular sclerosis. We hypothesize that these histologic features are indicative of nonfunctional glomeruli and may be associated with disconnection between the Bowman capsule and proximal tubule (atubular glomeruli). These glomeruli may not have effective filtration, despite some degree of circulation through the open capillary loops, and therefore are unable to accumulate immune complex deposits. If biopsies are small and only such glomeruli are available for immunofluorescence or electron microscopy examination, the absence of immune complex deposition in them should be evaluated carefully.

  19. Recycler barrier RF buckets

    Energy Technology Data Exchange (ETDEWEB)

    Bhat, C.M.; /Fermilab

    2011-03-01

    The Recycler Ring at Fermilab uses a barrier rf systems for all of its rf manipulations. In this paper, I will give an overview of historical perspective on barrier rf system, the longitudinal beam dynamics issues, aspects of rf linearization to produce long flat bunches and methods used for emittance measurements of the beam in the RR barrier rf buckets. Current rf manipulation schemes used for antiproton beam stacking and longitudinal momentum mining of the RR beam for the Tevatron collider operation are explained along with their importance in spectacular success of the Tevatron luminosity performance.

  20. Converse Barrier Certificate Theorem

    DEFF Research Database (Denmark)

    Wisniewski, Rafael; Sloth, Christoffer

    2013-01-01

    This paper presents a converse barrier certificate theorem for a generic dynamical system.We show that a barrier certificate exists for any safe dynamical system defined on a compact manifold. Other authors have developed a related result, by assuming that the dynamical system has no singular...... points in the considered subset of the state space. In this paper, we redefine the standard notion of safety to comply with generic dynamical systems with multiple singularities. Afterwards, we prove the converse barrier certificate theorem and illustrate the differences between ours and previous work...

  1. Converse Barrier Certificate Theorems

    DEFF Research Database (Denmark)

    Wisniewski, Rafael; Sloth, Christoffer

    2016-01-01

    This paper shows that a barrier certificate exists for any safe dynamical system. Specifically, we prove converse barrier certificate theorems for a class of structurally stable dynamical systems. Other authors have developed a related result by assuming that the dynamical system has neither...... singular points nor closed orbits. In this paper, we redefine the standard notion of safety to comply with dynamical systems with multiple singular elements. Hereafter, we prove the converse barrier certificate theorems and highlight the differences between our results and previous work by a number...

  2. Aluminum-containing dense deposits of the glomerular basement membrane: identification by energy dispersive X-ray analysis

    International Nuclear Information System (INIS)

    Smith, D.M. Jr.; Pitcock, J.A.; Murphy, W.M.

    1982-01-01

    Heavy metals, including gold, mercury, lead, bismuth, and cadmium, have the potential to cause renal disease. With the development of X-ray microanalysis, these heavy metals can now be identified in tissue deposits. This report describes a case of renal failure, probably related to dysproteinemia, in which granular, electron-opaque dense deposits were present in the glomerular basement membranes. Energy dispersive X-ray analysis demonstrated that these dense deposits contained aluminum. An analysis of this patient's history in relation to the current knowledge of aluminum metabolism suggests that the aluminum deposition occurred secondary to previous glomerular injury. This case emphasizes the need to utilize heavy metal identification technology whenever granular, electron-opaque dense deposits are identified and represents, to our knowledge, the first study to document aluminum deposits within the glomerular basement membrane of humans

  3. Pattern of glomerular disease in the Saudi population: A single-center, five-year retrospective study

    Directory of Open Access Journals (Sweden)

    Z Nawaz

    2013-01-01

    Full Text Available Glomerular diseases continue to be the leading cause of end-stage renal disease (ESRD globally. Hence, it is important to recognize the pattern of glomerular diseases in different geographical areas in order to understand the patho-biology, incidence and progression of the disorder. Published studies from different centers in Saudi Arabia have reported contradicting results. In this retrospective study, we report our experience at the Armed Forces Hospital, Riyadh, Saudi Arabia. A total of 348 native renal biopsies performed at our center on patients with proteinuria >1 g, hematuria and/or renal impairment during a period of 5 years (between January 2005 and December 2009 were studied by a histopathologist using light microscopy, immunofluorescence and electron microscopy, and were categorized. Results showed that primary glomerular disease accounted for 55.1% of all renal biopsies. The most common histological lesion was focal and segmental glomerulosclerosis (FSGS (27.6%, followed by minimal change disease (MCD (17.7% and membrano-proliferative glomerulonephritis (MPGN (13.0%. Secondary glomerular disease accounted for 37.9% of the glomerular diseases, with lupus nephritis (LN being the most common lesion (54.5%, followed by hypertensive nephrosclerosis (22%, post-infectious glomerulonephritis (7.5%, diabetic nephropathy (DN (6.8% and vasculitides (4.5%. Four percent of all biopsies turned out to be ESRD while biopsy was inadequate in 2.8% of the cases. In conclusion, our study showed that FSGS was the most common primary GN encountered, while LN was the most common secondary GN. We encountered 14 cases of crescentic glomerulonephritis. Also, the prevalence of MPGN, MCD, IgA nephropathy and membranous GN was many folds higher in males when compared with the Western data. We believe that it is mandatory to maintain a Saudi Arabian Renal Biopsy Registry to understand better the pattern of glomerular disease in the Saudi population and to follow

  4. Optimistic barrier synchronization

    Science.gov (United States)

    Nicol, David M.

    1992-01-01

    Barrier synchronization is fundamental operation in parallel computation. In many contexts, at the point a processor enters a barrier it knows that it has already processed all the work required of it prior to synchronization. The alternative case, when a processor cannot enter a barrier with the assurance that it has already performed all the necessary pre-synchronization computation, is treated. The problem arises when the number of pre-sychronization messages to be received by a processor is unkown, for example, in a parallel discrete simulation or any other computation that is largely driven by an unpredictable exchange of messages. We describe an optimistic O(log sup 2 P) barrier algorithm for such problems, study its performance on a large-scale parallel system, and consider extensions to general associative reductions as well as associative parallel prefix computations.

  5. Barrier Infrared Detector (BIRD)

    Data.gov (United States)

    National Aeronautics and Space Administration — A recent breakthrough in MWIR detector design, has resulted in a high operating temperature (HOT) barrier infrared detector (BIRD) that is capable of spectral...

  6. Protective barrier development: Overview

    International Nuclear Information System (INIS)

    Wing, N.R.; Gee, G.W.

    1990-01-01

    Protective barrier and warning marker systems are being developed to isolate wastes disposed of near the earth's surface at the Hanford Site. The barrier is designed to function in an arid to semiarid climate, to limit infiltration and percolation of water through the waste zone to near-zero, to be maintenance free, and to last up to 10,000 yr. Natural materials (e.g., fine soil, sand, gravel, riprap, clay, asphalt) have been selected to optimize barrier performance and longevity and to create an integrated structure with redundant features. These materials isolate wastes by limiting water drainage; reducing the likelihood of plant, animal, and human intrusion; controlling emission of noxious gases; and minimizing erosion. Westinghouse Hanford Company and Pacific Northwest Laboratory efforts to assess the performance of various barrier and marker designs will be discussed

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

    DEFF Research Database (Denmark)

    Olsen, N V; Ladefoged, S D; Feldt-Rasmussen, B

    1989-01-01

    The renal clearance of endogenous creatinine (CCr), sodium (CNa) and lithium (CLi) was determined before and after a single intravenous bolus of cimetidine in nine renal transplant recipients. The glomerular filtration rate (GFR) was measured with 125I-iothalamate clearance (CTh). The initial CCr...... of sodium decreased throughout the study (p less than 0.05); CLi was unchanged. In conclusion cimetidine, when measured during 1-h clearance periods, interferes with tubular creatinine secretion in the denervated kidney of transplant recipients without affecting the glomerular filtration rate or proximal...

  8. Tubular markers do not predict the decline in glomerular filtration rate in type 1 diabetic patients with overt nephropathy

    DEFF Research Database (Denmark)

    Nielsen, Stine E; Andersen, Steen; Zdunek, Dietmar

    2011-01-01

    of neutrophil gelatinase-associated lipocalin (NGAL), liver-fatty acid-binding protein (LFABP), and kidney injury molecule-1 (KIM-1) in a 3-year intervention study of 63 type 1 diabetic patients with kidney disease. The baseline mean glomerular filtration rate (GFR) was 87 ml/min per 1.73 m(2) and urinary......Recent studies have shown that both glomerular and tubulointerstitial damage are important factors in the pathophysiology and progression of diabetic nephropathy. To examine whether markers of tubular damage are useful in monitoring the progression of disease, we measured urinary levels...

  9. Sleep duration and quality in relation to chronic kidney disease and glomerular hyperfiltration in healthy men and women.

    Directory of Open Access Journals (Sweden)

    Chan-Won Kim

    Full Text Available It is unclear whether sleep duration and quality are associated with chronic kidney disease (CKD and glomerular hyperfiltration. The aim of this study was to examine the association of sleep duration and quality with CKD and glomerular hyperfiltration in young and middle-aged adults.We conducted a cross-sectional study of men and women who underwent a health checkup examination, including assessment of sleep duration and quality (n = 241,607. Chronic kidney disease (CKD was defined as an estimated glomerular filtration rate (eGFR less than 60 ml/min/1.73 m2, and glomerular hyperfiltration was defined as eGFR above the age-/sex-specific 95th percentile.In a multinomial logistic regression analysis adjusting for relevant confounders, the adjusted prevalence ratios for CKD (95% confidence interval comparing sleep durations of ≤ 5, 6, 8, and 9 hours with 7 hours were 1.22 (0.95-1.55, 0.93 (0.75-1.14, 0.97 (0.75-1.26, and 1.56 (1.06-2.30 in men and 0.98 (0.68-1.43, 1.03 (0.72-1.46, 1.39 (0.97-2.00, and 1.31 (0.78-2.22 in women, respectively. The corresponding prevalence ratios (95% confidence interval for glomerular hyperfiltration were 1.00 (0.93-1.08, 0.97 (0.91-1.03, 1.03 (0.94-1.13, and 1.39 (1.13-1.72 in men and 1.04 (0.95-1.14, 0.96 (0.90-1.04, 1.11 (1.02-1.20, and 1.28 (1.14-1.45 in women, respectively. Poor subjective sleep quality was associated with glomerular hyperfiltration in men and women.In this large study of young and middle-aged adults, we found that long sleep duration was associated with CKD and glomerular hyperfiltration. Additionally, poor subjective sleep quality was associated with increased prevalence of glomerular hyperfiltration, suggesting the importance of adequate quantity and quality of sleep for kidney function.

  10. Sleep duration and quality in relation to chronic kidney disease and glomerular hyperfiltration in healthy men and women.

    Science.gov (United States)

    Kim, Chan-Won; Chang, Yoosoo; Sung, Eunju; Yun, Kyung Eun; Jung, Hyun-Suk; Ko, Byung-Joon; Kwon, Min-Jung; Hyun, Young Youl; Lee, Kyu-Beck; Kim, Hyang; Shin, Hocheol; Ryu, Seungho

    2017-01-01

    It is unclear whether sleep duration and quality are associated with chronic kidney disease (CKD) and glomerular hyperfiltration. The aim of this study was to examine the association of sleep duration and quality with CKD and glomerular hyperfiltration in young and middle-aged adults. We conducted a cross-sectional study of men and women who underwent a health checkup examination, including assessment of sleep duration and quality (n = 241,607). Chronic kidney disease (CKD) was defined as an estimated glomerular filtration rate (eGFR) less than 60 ml/min/1.73 m2, and glomerular hyperfiltration was defined as eGFR above the age-/sex-specific 95th percentile. In a multinomial logistic regression analysis adjusting for relevant confounders, the adjusted prevalence ratios for CKD (95% confidence interval) comparing sleep durations of ≤ 5, 6, 8, and 9 hours with 7 hours were 1.22 (0.95-1.55), 0.93 (0.75-1.14), 0.97 (0.75-1.26), and 1.56 (1.06-2.30) in men and 0.98 (0.68-1.43), 1.03 (0.72-1.46), 1.39 (0.97-2.00), and 1.31 (0.78-2.22) in women, respectively. The corresponding prevalence ratios (95% confidence interval) for glomerular hyperfiltration were 1.00 (0.93-1.08), 0.97 (0.91-1.03), 1.03 (0.94-1.13), and 1.39 (1.13-1.72) in men and 1.04 (0.95-1.14), 0.96 (0.90-1.04), 1.11 (1.02-1.20), and 1.28 (1.14-1.45) in women, respectively. Poor subjective sleep quality was associated with glomerular hyperfiltration in men and women. In this large study of young and middle-aged adults, we found that long sleep duration was associated with CKD and glomerular hyperfiltration. Additionally, poor subjective sleep quality was associated with increased prevalence of glomerular hyperfiltration, suggesting the importance of adequate quantity and quality of sleep for kidney function.

  11. Semiautomated quantitative image analysis of glomerular immunohistochemistry markers desmin, vimentin, podocin, synaptopodin and WT-1 in acute and chronic rat kidney disease models.

    Science.gov (United States)

    Funk, J; Ott, V; Herrmann, A; Rapp, W; Raab, S; Riboulet, W; Vandjour, A; Hainaut, E; Benardeau, A; Singer, T; Jacobsen, B

    2016-03-01

    Five different glomerular immunohistochemistry markers were evaluated and compared in four different acute and chronic rat kidney disease models. Progression of glomerular or podocyte damage was shown in the puromycin aminonucleoside nephrosis (PAN) and Zucker fatty/spontaneously hypertensive heart failure F1 hybrid (ZSF1) rat model. Progression and prevention of glomerular damage was demonstrated in the Zucker diabetic fatty (ZDF) and Dahl salt-sensitive (Dahl SS) rat. Immunohistochemistry was performed for desmin, vimentin, podocin, synaptopodin and Wilms tumor protein-1 (WT-1), and evaluation of glomerular immunohistochemistry markers was done by semiautomated quantitative image analysis. We found desmin and WT-1 as the most sensitive markers for podocyte damage in both acute and chronic glomerular damage followed by vimentin, podocin and synaptopodin. We were able to demonstrate that early podocyte damage as shown by increased desmin and vimentin staining together with either a phenotypic podocyte change or podocyte loss (reduced numbers of WT-1-stained podocytes) drives the progression of glomerular damage. This is followed by a reduction in podocyte-specific proteins such as podocin and synaptopodin. Our report describes the different sensitivity of glomerular or podocyte markers and gives future guidance for the selection of the most sensitive markers for efficacy testing of new drugs as well as for the selection of tissue-based toxicity markers for glomerular or podocyte injury. In addition to functional clinical chemistry markers, desmin and WT-1 immunohistochemistry offers reliable and valuable data on the morphologic state of podocytes.

  12. Glomerular filtration rate and segmental tubular function in the early phase after transplantation/uninephrectomy in recipients and their living-related kidney donors

    DEFF Research Database (Denmark)

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

    1994-01-01

    1. Glomerular filtration rate and sequential tubular function were investigated in 18 adult renal transplant recipients and in their matched, adult living-related kidney donors before and 5 days after transplantation/uninephrectomy. At day 54, 13 donors and 11 recipients were re-investigated. Six......1. Glomerular filtration rate and sequential tubular function were investigated in 18 adult renal transplant recipients and in their matched, adult living-related kidney donors before and 5 days after transplantation/uninephrectomy. At day 54, 13 donors and 11 recipients were re......-investigated. Sixteen of these constituted eight matched pairs. This reduction in the study population was caused by the application of two withdrawal criteria. 2. In the recipients glomerular filtration rate was unchanged at day 5 and had increased to 61 ml/min at day 54 (P glomerular filtration....../min to 2.10 ml/min at day 54 (P glomerular filtration rate, lithium clearance, absolute and fractional proximal...

  13. Aging and physiological changes of the kidneys including changes in glomerular filtration rate.

    Science.gov (United States)

    Musso, Carlos G; Oreopoulos, Dimitrios G

    2011-01-01

    In addition to the structural changes in the kidney associated with aging, physiological changes in renal function are also found in older adults, such as decreased glomerular filtration rate, vascular dysautonomia, altered tubular handling of creatinine, reduction in sodium reabsorption and potassium secretion, and diminished renal reserve. These alterations make aged individuals susceptible to the development of clinical conditions in response to usual stimuli that would otherwise be compensated for in younger individuals, including acute kidney injury, volume depletion and overload, disorders of serum sodium and potassium concentration, and toxic reactions to water-soluble drugs excreted by the kidneys. Additionally, the preservation with aging of a normal urinalysis, normal serum urea and creatinine values, erythropoietin synthesis, and normal phosphorus, calcium and magnesium tubular handling distinguishes decreased GFR due to normal aging from that due to chronic kidney disease. Copyright © 2011 S. Karger AG, Basel.

  14. Current status and methodological aspects on the measurement of glomerular filtration rate

    International Nuclear Information System (INIS)

    Froissart, M.; Hignette, C.; Kolar, P.; Prigent, A.; Paillard, M.

    1995-01-01

    Determination of the glomerular filtration rate (GFR) contribute to our understanding of kidney physiology and pathophysiology . Moreover, determination of GFR is of clinical importance in assessing the diagnosis and the progression of renal disease. The purpose of this article is to review the technical performance and results of GFR measurements, including the classical inulin clearance technique and more recent alternative clearance techniques using radioisotope-labelled filtration markers, bolus infusion and spontaneous bladder emptying. Some simplified techniques avoiding urinary collection are also described. We conclude that estimation of GFR from renal and in some cases plasmatic clearances is accurate and more convenient than the classical inulin clearance technique. Such measurements of GFR should be included both in clinical practice and clinical research. (authors). 80 refs., 5 figs., 1 tab

  15. Estimation of glomerular filtration rate by 99mTc-DTPA dynamic renography

    International Nuclear Information System (INIS)

    Qu Wanying

    1989-01-01

    Estimation of glomerular filtration rate (GFR) by 99m Tc-DTPA dynamic renography was performed in 397 adult patients. The entire study requires only 20 minutes but obtained simultaneously the renal blood flow, renogram, renal morphology study and GFR. The GFR was calculated according to Gate's formula. Creatinine clearance values were also determined compared with GFR in 18 of the patients. The author found they correlated well each other (r = 0.93). Normal data of 14 parameters were derived from the blood flow curve. The normal value of GFR was 112.11 +- 19.05 ml/min and no significant difference in GFR of both kidney was revealed. In patients of urinary stones, essential hypertension, chronic glomerulonephritis and chronic pyelonephritis etc., there were significant lowered GFR denoted. The results showed that the estimation of GFR by 99m Tc-DTPA dynamic renography was reliable, safe and conventient method, and suitable to replace creatinine in clinical study

  16. Autoregulation of renal blood flow and glomerular filtration rate in the pregnant rabbit

    International Nuclear Information System (INIS)

    Woods, L.L.; Mizelle, H.L.; Hall, J.E.

    1987-01-01

    The authors purpose was to determine whether renal autoregulatory capability is retained in pregnancy despite the marked renal vasodilation that occurs at this time. Renal blood flow and glomerular filtration rate (GFR) were measured in anesthetized pregnant (22-27 days gestation) and nonpregnant rabbits during step reductions in renal perfusion pressure from control (100 +/- 3 mmHg) to 50 mmHg. Control renal blood flow and GFR were significantly higher in pregnant animals. Filtration fraction was also significantly elevated in pregnant animals. During step reductions in renal perfusion pressure, renal blood flow was well autoregulated down to ∼70 mmHg in both nonpregnant and pregnant animals. Likewise, GFR was also well autoregulated, falling by 10 +/- 2 and 8 +/- 3% in nonpregnant and pregnant animals, respectively, when perfusion pressure was reduced from 90 to 70 mmHg. These results suggest that renal autoregulation is preserved in pregnancy despite the fact that the renal circulation is already markedly vasodilated

  17. A re-evaluation of the determinants of glomerular filtration rate

    DEFF Research Database (Denmark)

    Karlsen, F M; Holstein-Rathlou, N H; Leyssac, P P

    1995-01-01

    Several factors are potentially able to change the glomerular filtration rate (GFR) and thereby participate in its regulation, but only a few factors seem to be physiologically important. The variable nature of proximal tubular pressure should be recognized as important in the regulation of GFR...... mechanism, while larger changes in the APR cause near parallel changes in the GFR mainly because of the effect on tubular pressure. The hydraulic resistance in the distal nephron segments is an additional factor in regulating GFR, through its effect on proximal tubular pressure. The stimulus to the TGF...... advocated here, TGF-mediated changes in afferent arteriolar resistance and angiotensin-mediated changes in efferent arteriolar resistance and APR cooperate in counteracting perturbations in proximal tubular pressure and Henle loop flow. However, because of the biphasic proximal effect of angiotensin II...

  18. Glomerular filtration in kidney recipients measured by plasma clearance of 169Yb-DTPA

    International Nuclear Information System (INIS)

    Stribrna, J.; Oppelt, A.; Jirickova, E.; Janata, V.; Kocandrle, V.; Sup, I.; Woller, P.; Franke, W.G.

    1986-01-01

    Values of 169 Yb-DTPA clearance (C DTPA ) calculated after a single injection were compared in 26 recipients of kidneys with renal clearance of inulin (C in ), polyfructosan S (C pf ) and creatinine (C cr ). In 21 patients the examinations were made simultaneously, in 5 patients C DTPA was measured within a short interval after the examination of renal clearance. The mean C DTPA values did not significantly differ from C cr but were significantly higher (p in and C pf (by 33% on average). Investigation of changes in C DTPA as compared with C in and C pf showed no significant difference in glomerular filtration (GF). This was measured using inulin and polyfructosan. The results showed that the differing molecular weight of inulin and polyfructosan S had no detectable effect on the GF of kidney recipients. The plasma clearance of 169 Yb-DTPA similarly to C cr overestimates the GF measured by inulin and polyfructosan clearance. (author)

  19. Effect of Cisplatin on Glomerular Filtration Rate and Effective Renal Plasma Flow

    International Nuclear Information System (INIS)

    Lim, Sang Moo; Hong, Sung Woon; Kim, Young Hyun; Hong, Weon Seon; Song, Jae Kwan; Kim, Young Whan; Lee, Jhin Oh; Kang, Tae Woong

    1989-01-01

    While cisplatin has been widely used in the treatment of a variety of cancers, nephrotoxicity is one of the major problems which frequently limit clinical usefulness of cisplatin. This study has been conducted to investigate nephrotoxicity of cisplatin in terms of changes in glomerular filtration rate (GFR) and effective renal plasma flow (EFPF) measured by the simultaneous use of 99m Tc-DTPP and 131 I-OIH, before and after administration of cisplatin, in 12 patients with lung cancer and four patients with esophageal cancer. Cisplatin was administrated at total doses of 75-100 mg/m 2 with two hour hydration and diuresis method. GFR determined by the use of 99m Tc-DTPA had a good correlation with 24-hour creatinine clearance rate (r=0.77, p 99m Tc-DTPA and 131 I-OIH was a useful tool for the measurement of GFR and ERPF respectively.

  20. Glomerular size and charge selectivity in insulin-dependent diabetes mellitus

    DEFF Research Database (Denmark)

    Deckert, T; Feldt-Rasmussen, B; Djurup, R

    1988-01-01

    The pathogenesis of clinical nephropathy in Type 1 (insulin-dependent) diabetes was investigated by measuring renal fractional clearances of albumin, total IgG, IgG4 and beta 2-microglobulin, four plasma proteins which differ in size and charge. Seventy patients and eleven control subjects were...... studied. In diabetic patients with normal urinary albumin excretion (less than 30 mg/24 hr), fractional IgG clearance was two to three times higher than in control subjects, whereas fractional clearance of the anionic plasma proteins IgG4 and albumin was similar to that of control subjects....... These alterations indicate an increase in anionic pore charge within the glomerular basement membrane concomitant with an increase in either pore size or impairment of tubular reabsorption. Diabetic patients, whose urinary albumin excretion has started to rise (30 to 100 mg/24 hr), had unchanged fractional Ig...

  1. [Estimating glomerular filtration rate in 2012: which adding value for the CKD-EPI equation?].

    Science.gov (United States)

    Delanaye, Pierre; Mariat, Christophe; Moranne, Olivier; Cavalier, Etienne; Flamant, Martin

    2012-07-01

    Measuring or estimating glomerular filtration rate (GFR) is still considered as the best way to apprehend global renal function. In 2009, the new Chronic Kidney Disease Epidemiology (CKD-EPI) equation has been proposed as a better estimator of GFR than the Modification of Diet in Renal Disease (MDRD) study equation. This new equation is supposed to underestimate GFR to a lesser degree in higher GFR levels. In this review, we will present and deeply discuss the performances of this equation. Based on articles published between 2009 and 2012, this review will underline advantages, notably the better knowledge of chronic kidney disease prevalence, but also limitations of this new equation, especially in some specific populations. We eventually insist on the fact that all these equations are estimations and nephrologists should remain cautious in their interpretation. Copyright © 2012 Association Société de néphrologie. Published by Elsevier SAS. All rights reserved.

  2. Tracing the origin of glomerular extracapillary lesions from parietal epithelial cells.

    Science.gov (United States)

    Smeets, Bart; Uhlig, Sandra; Fuss, Astrid; Mooren, Fieke; Wetzels, Jack F M; Floege, Jürgen; Moeller, Marcus J

    2009-12-01

    Cellular lesions form in Bowman's space in both crescentic glomerulonephritis and collapsing glomerulopathy. The pathomechanism and origin of the proliferating cells in these lesions are unknown. In this study, we examined proliferating cells by lineage tracing of either podocytes or parietal epithelial cells (PECs) in the nephrotoxic nephritis model of inflammatory crescentic glomerulonephritis. In addition, we traced the fate of genetically labeled PECs in the Thy-1.1 transgenic mouse model of collapsing glomerulopathy. In both models, cellular bridges composed of PECs were observed between Bowman's capsule and the glomerular tuft. Genetically labeled PECs also populated larger, more advanced cellular lesions. In these lesions, we detected de novo expression of CD44 in activated PECs. In contrast, we rarely identified genetically labeled podocytes within the cellular lesions of crescentic glomerulonephritis. In conclusion, PECs constitute the majority of cells that compose early extracapillary proliferative lesions in both crescentic glomerulonephritis and collapsing glomerulopathy, suggesting similar pathomechanisms in both diseases.

  3. Incidence and prognostic importance of glomerular crescents in renal diseases of childhood.

    Science.gov (United States)

    Miller, M N; Baumal, R; Poucell, S; Steele, B T

    1984-01-01

    The renal biopsies of 372 children with various glomerular disorders were reviewed and crescent formation was seen in 56 cases (15%). Four disorders, i.e. systemic lupus erythematosus, membranoproliferative glomerulonephritis (MPGN) types I and II and Henoch-Schönlein disease accounted for 74% of 10 diagnostic categories. Idiopathic rapidly progressive glomerulonephritis (RPGN) was seen in only 2 cases. Crescents associated with MPGN types I or II or idiopathic RPGN had a bad renal prognosis, whereas the presence of crescents in other disorders did not necessarily affect the renal outcome. Immunofluorescent and electron microscopic findings are essential to distinguish many conditions which may be associated with crescent formation in childhood renal disease.

  4. Correlation of Cystatin-C with Glomerular Filtration Rate by Inulin Clearance in Pregnancy

    Science.gov (United States)

    Saxena, Aditi R.; Karumanchi, S. Ananth; Fan, Shu-Ling; Horowitz, Gary L.; Seely, Ellen W.

    2012-01-01

    Objective To test utility of cystatin-C as a marker of glomerular filtration rate during pregnancy, we performed serial correlations with inulin clearance during pregnancy and postpartum. Methods Twelve subjects received inulin infusions and serum cystatin-C at three time points. Pearson's correlation coefficient was calculated. Results Cystatin-C levels ranged 0.66 to 1.48 mg/L during pregnancy, and 0.72 to 1.26 mg/L postpartum. Inulin clearance ranged 130 to 188 ml/min during pregnancy, and 110 to 167 ml/min postpartum. Cystatin-C did not correlate with inulin clearance at any time point. Conclusion Serum cystatin-C did not correlate with inulin clearance during pregnancy or postpartum. PMID:22008011

  5. Galectin-3 binding protein links circulating microparticles with electron dense glomerular deposits in lupus nephritis

    DEFF Research Database (Denmark)

    Nielsen, C T; Østergaard, O; Rekvig, O P

    2015-01-01

    , explore putative clinical correlates, and examine if G3BP is present in immune complex deposits in kidney biopsies from patients with lupus nephritis. METHODS: Numbers of annexin V-binding and G3BP-exposing plasma microparticles from 56 SLE patients and 36 healthy controls were determined by flow...... in kidney biopsies from one non-SLE control and from patients with class IV (n = 2) and class V (n = 1) lupus nephritis using co-localization immune electron microscopy. RESULTS: Microparticle-G3BP, microparticle-C1q and microparticle-immunoglobulins were significantly (P ... activity were found. Immune electron microscopy showed co-localization of G3BP with in vivo-bound IgG in glomerular electron dense immune complex deposits in all lupus nephritis biopsies. CONCLUSIONS: Both circulating microparticle-G3BP numbers as well as G3BP expression are increased in SLE patients...

  6. Glomerular filtration rate estimation in renal transplant patients based on serum cystatin-C levels: comparison with other markers of glomerular filtration rate.

    Science.gov (United States)

    Visvardis, G; Griveas, I; Zilidou, R; Papadopoulou, D; Mitsopoulos, E; Kyriklidou, P; Manou, E; Ginikopoulou, E; Meimaridou, D; Pavlitou, A; Sakellariou, G

    2004-01-01

    The assessment of glomerular filtration rate (GFR) is the most commonly used test of renal function. Cystatin-C, a cysteine protease inhibitor, which can be measured by light-scattering immunoassay, possesses many of the attributes required of the ideal GFR marker. Conversely, many endogenous markers that are widely used for the estimation of GFR such as serum creatinine (SCr) are not ideal. The present study was undertaken to evaluate the clinical application of serum cystatin-C (CysC) as a new marker of GFR in renal transplant patients. Eighteen patients (9 men) were enrolled in the study (mean age: 46.35, range: 31-67 years) to measure serum CysC levels and compare them, with SCr, creatinine clearance (CCr), as well as the Cockcroft-Gault equation (CG) or the MDRD as indicator of GFR. Spearman's correlation coefficient was used to determine the relationship between CysC and other markers. There was a significant negative correlation between serum CysC and CCr (r = -0.768). Moreover, the CysC level was negatively correlated with CG (r = -0.854), positively correlated with SCr (r = 0.629), and negatively correlated with MDRD (r = -0.604). These results indicate that measurement of serum cystatin-C was useful and accurate to estimate GFR in renal transplant patients. The recent literature confirms our data although there are concerns about nonrenal influence on this test. Although serum CysC can generally be recommended as a marker for GFR, our study is still in progress seeking to validate the conclusions in a larger number of patients.

  7. Radiation nephropathy in the rhesus monkey: morphometric analysis of glomerular and tubular alterations

    International Nuclear Information System (INIS)

    Clifton Stephens, L.; Robbins, Mike E.C.; Johnston, Dennis A.; Thames, Howard D.; Price, Roger E.; Peters, Lester J.; Kian Ang, K.

    1995-01-01

    Purpose: The morphologic responses of the monkey kidney glomeruli and tubules to fractionated irradiation were assessed. Methods and Materials: Both kidneys of adult female rhesus monkeys were irradiated with doses of γ-rays ranging from 24 Gy in 12 fractions up to 36 Gy in 18 fractions. Serial renal biopsies were taken between 1 and 12 weeks after irradiation. The kidneys were removed at necropsy 16-23 weeks after irradiation. Glomeruli were assessed for the presence of pathologic features, including intercapillary eosinophilic material, ectatic capillaries, thrombi, hemorrhage, adhesions, and sclerosis. The relative proportion of renal cortex occupied by glomeruli, interstitium, or tubules was determined using a Chalkley point grid. Tubules were further scored as being either normal or abnormal in appearance. Results: Examination of the renal biopsies revealed that progressive glomerular lesions were evident within 4-12 weeks after irradiation. Tubular changes were mild and focal. Morphometric analysis of whole kidneys removed at necropsy demonstrated that numbers of glomeruli with ectatic capillaries, thrombi, and hemorrhage were significantly different from controls at 16-23 weeks after irradiation by all of the doses in the range of 24 to 36 Gy. A significant (p < 0.05) increase in the relative proportion of renal cortex occupied by glomeruli and interstitium was indicative of tubule loss. Further analysis of these tubular changes revealed a highly significant (p < 0.001) dose-dependent increase in the proportion of abnormal to normal tubules. Thus following a dose of 24 Gy in 12 fractions, the ratio of abnormal:normal tubules was approximately 1:2; after 36 Gy in 18 fractions the ratio was 3:1. Conclusions: Glomeruli appeared to be very radiosensitive because after the clinically relevant dose of 24 Gy in 12 fractions essentially all glomeruli were altered in the irradiated kidneys as compared to controls. Thus, efforts aimed at increasing the threshold dose

  8. Clinical outcome of patients with coexistent antineutrophil cytoplasmic antibodies and antibodies against glomerular basement membrane.

    Science.gov (United States)

    Lindic, Jelka; Vizjak, Alenka; Ferluga, Dusan; Kovac, Damjan; Ales, Andreja; Kveder, Radoslav; Ponikvar, Rafael; Bren, Andrej

    2009-08-01

    Antineutrophil cytoplasmic antibodies (ANCA) and antibodies against glomerular basement membrane (anti-GBM) rarely coexist. Both antibodies may be associated with rapidly progressive glomerulonephritis and pulmonary hemorrhage. We describe the clinical, serological and histological features of our patients with dual antibodies. From 1977 to 2008, 48 patients with anti-GBM antibody-associated renal disease were observed. Eight out of the 30 tested patients (26.7%), all females, had positive myeloperoxidase (MPO)-ANCA coexistent with anti-GBM antibodies. The patients' mean age was 63.4 +/- 7.8 years. Five presented with pulmonary-renal syndrome, all but one were dialysis-dependent on admission. They had constitutional symptoms and different organ involvement. The kidney biopsies revealed intense linear staining for immunoglobulin G and C3 along the glomerular and distal tubular basement membrane associated with irregular diffuse or focal extracapillary crescentic glomerulonephritis with necrosis of varying extent. Lesions of varying ages were characteristically expressed. Seven patients were treated with methylprednisolone and plasma exchange, four with cyclophosphamide, and one with intravenous immunoglobulin. After 28-74 months, there were three dialysis-dependent survivors and one patient with stable chronic renal disease. Two clinical relapses with pulmonary involvement and MPO-ANCA positivity without anti-GBM antibodies occurred in two dialysis-dependent patients. In summary, screening for ANCA and anti-GBM antibodies should be undertaken in patients with clinical signs of systemic vasculitis. In dialysis-dependent patients, the goal of treatment is to limit the damage of other involved organs and not to preserve renal function. Careful follow-up is necessary due to the relapsing nature of the ANCA component of the disease.

  9. Effects of fish oil on glomerular function in rats with diabetes mellitus.

    Science.gov (United States)

    Sinha, A K; Scharschmidt, L A; Neuwirth, R; Holthofer, H; Gibbons, N; Arbeeny, C M; Schlondorff, D

    1990-07-01

    The mechanisms responsible for hyperfiltration in diabetes mellitus (DM) as well as for the initiation and progression of diabetic nephropathy are not fully elucidated. Enhanced prostaglandin E2 (PGE2) production has been invoked in the former and thromboxane (TXB2) and hyperlipidemia in the latter. Fish oil (FO)-enriched diets can favorably alter eicosanoid synthesis and serum lipid profiles. We therefore examined the effects of a FO-enriched diet on glomerular filtration (GFR), proteinuria, glomerular eicosanoid production, and serum lipids in rats with streptozotocin-induced DM (STZ-DM). Groups of 5-8 rats with STZ-DM were maintained on low insulin and then pair-fed with isocaloric diets enriched with either FO (20% w/w) or beef tallow (BT; 20% w/w). GFR was determined in the same animals at onset of diet and after 8 and 20 weeks on the respective diets by [14C]inulin clearance using implanted osmotic minipumps each time. Significant hyperfiltration was present initially and GFR did not change on either diet for 20 weeks, in spite of a significant and greater than 50% decrease in all prostaglandins (PGE2, TXB2, PGF2 alpha, 6-keto, PGF1 alpha) produced by glomeruli isolated from DM/FO as compared to DM/BT or control rats. FO diet completely corrected the hypertriglyceridemia of diabetes and significantly reduced the mild and early proteinuria of DM. The decrease in proteinuria and the correction of hyperlipidemia of DM by a FO-enriched diet may be beneficial in the long term not only for the development of diabetic glomerulopathy, but also for the accelerated atherosclerosis of DM.

  10. Glomerular deposition and urinary excretion of complement factor H in idiopathic membranous nephropathy.

    Science.gov (United States)

    Endo, Morito; Fuke, Yoshinobu; Tamano, Mariko; Hidaka, Mutsuko; Ohsawa, Isao; Fujita, Takayuki; Ohi, Hiroyuki

    2004-01-01

    The complement system plays an important role in the pathogenesis of membranous nephropathy (MN). In order to elucidate the regulatory mechanism of complement activation, we demonstrated glomerular deposition and urinary excretion of complement factor H, which controls the alternative pathway and the amplification loop at the C3 step, in patients with idiopathic MN. Renal biopsy specimens from 20 patients with idiopathic MN were studied immunohistochemically using monoclonal antibodies against complement components including factor H. SDS-PAGE and Western blotting analysis of urine samples were performed, and the urinary excretion of factor H and C5b-9 were measured by quantitative sandwich ELISA. Intense glomerular deposition of factor H was observed with C3b.C3c and C5b-9 at an early stage of the disease. Factor H was detected in Western blots of urine samples, but factor H-like protein 1 (FHL-1) was not. The mean level of urinary factor H was elevated (86.30 +/- 21.93 U/mg urinary creatinine) in comparison to that of normal controls (4.76 +/- 1.03 U/mg urinary creatinine). Urinary factor H level exhibited no correlation with clinical parameters; however, a negative correlation was found between urinary C5b-9/factor H and creatinine clearance (r = 0.662, p 150-kD protein. There was no evidence to suggest that FHL-1 is synthesized at the site of inflammation. The urinary C5b-9 to urinary factor H ratio is indicative of the degree of ongoing complement activation in the glomeruli and complement-mediated renal injury. These findings suggest that factor H contributes to the control mechanism of in situ complement activation and prevents renal damage in idiopathic MN. Copyright 2004 S. Karger AG, Basel

  11. A “Mini-Epidemic” of anti-glomerular basement membrane disease: Clinical and epidemiological study

    Directory of Open Access Journals (Sweden)

    Umesh Lingaraj

    2017-01-01

    Full Text Available Acute glomerulonephritis due to anti-glomerular basement membrane (anti-GBM antibody disease is rare, estimated to occur in fewer than one case per million population and accounts for less than 20% of rapidly progressive glomerulonephritis. The prevalence among patients evaluated for potential glomerular disease is lower. It accounts for fewer than 3% of all kidney biopsies done with crescentic glomerulonephritis. Cases of anti-GBM disease occurring in a cluster have rarely been reported. All biopsy proven anti-GBM disease cases were collected from January 2015 to March 2015 at our Institute. All cases were analyzed for demographic and clinical profile, pathological findings, treatment received and for any common environmental antigenic source. A total of 11 new biopsy proven anti-GBM cases were seen within a span of three months. Age group varied from 17–80 years. Seven were males and four were females. All were dialysis dependent at presentation. Seven had active cellular crescents, and four had fibrocellular. Only one patient was a smoker and none had a history of exposure to any forms of hydrocarbons. The peak seen from January 2015 to March 2015 does not correlate with any of seasonal occurrence of infections in southern India. Although there was clustering of cases to southern territories of Karnataka state, no common etiological agents could be identified. No patient had any previous urological surgeries. All patients received methylprednisolone with plasmapheresis 5–7 sessions and cyclophosphamide. All 11 patients were dialysis dependent at the end of three months. We conclude anti-GBM disease cannot be regarded as a rare cause of renal failure and lung hemorrhage. The occurrence of such epidemic within a short period suggests a possible unidentified environmental factor like infection or occupational agents as inciting agents. Identification of such inciting agents could help us in instituting appropriate preventing measures.

  12. TREATMENT OF CHILDREN WITH FOCAL SEGMENTAL GLOMERULAR SCLEROSIS WITH CYCLOSPORINE A

    Directory of Open Access Journals (Sweden)

    O.V. Komarova

    2009-01-01

    Full Text Available The article demonstrates successful experience of treatment of focal segmental glomerular sclerosis (FSGS with cyclosporine A in children. 25 children over the age 1,5–16 years old with FSGS were treated with cyclosporine A in medium dose 4–5 mg/kg combined with prednisolone 1–1,5 mg/kg every other day. Pulse treatment with methylprednisolone 30 mg/kg every other day, in total 3–9 injections, was administrated for the purpose of remission induction. After 5 months of treatment with cyclosporine A complete clinical and laboratory remission of steroid-resistance nephritic syndrome (SRNS was achieved in 9 (36% patients, partial response was registered in 6 (24% patients, maintenance of SRNS activity was detected in 10 (40% cases. After the year of treatment complete remission was shown in 13 (52% children, partial response — in 5 (20% patients, and absence of effect was registered in 7 (28% cases. In 56% of cases, the treatment with steroids was completely stopped after achievement of SRNS remission within administration of cyclosporine A. At the present times, authors observe 14 children, whose duration of treatment with cyclosporine A is 2 years. 12 patients remain previously achieved complete or partial remission of nephritic syndrome without decrease of nitrogen excretion function of kidneys. 9 patients underwent repeated biopsy of kidneys for the exclusion of nephrotoxic effect of cyclosporine A. The results of biopsy allowed prolongation of therapy: in 6 children the previous dose maintained, and 3 children got double decreased dose. Thus, the treatment with cyclosporine A is effective in 76% of patients with FSGS. Prolongation of treatment with cyclosporine A up to 2 years and more is possible in conditions of regular diagnostic of kidneys function and absence of its nephrotoxic effect signs, according to a data from repeated biopsy.Key words: children, focal segmental glomerular sclerosis, cyclosporine, methylprednisolone

  13. Glomerular filtration and tubular secretion of MAG-3 in the rat kidney

    International Nuclear Information System (INIS)

    Mueller-Suur, R.M.; Mueller-Suur, C.

    1989-01-01

    Technetium-99m mercaptoacetyltriglycine (MAG-3) has recently been introduced as a new radiopharmaceutical for dynamic renal scintigraphy. To elucidate the mechanism of renal excretion, micropuncture experiments were performed in rat kidneys for direct measurements of glomerular filtration and tubular secretory capacity. Fluid of Bowman space was collected from superficial glomeruli and analyzed for its contents of [99mTc]MAG-3, [125I]hippurate and [3H]inulin during constant infusion of these compounds. The ratio of activity of ultrafiltrate to that of arterial plasma was 0.23 for MAG-3, 0.68 for hippurate and 1.04 for inulin which demonstrates that the filtrated amount of MAG-3 is only 23% of that of inulin, presumably because of higher plasma protein binding which was also measured in vitro and found to be 80 +/- 1.5% for MAG-3 and 32 +/- 2% for [125I]hippurate. Proximal and distal tubules were also micropunctured and their tubular fluid as well as the final urine analyzed for the activity of hippurate and MAG-3. The tubular fluid to plasma ratio values along the nephron and in the final urine were all lower for MAG-3 than for hippurate, indicating a lower secretory capacity. From measurements of whole renal clearance, GFR and plasma protein binding the filtered amount of MAG-3 was 0.26 and of hippurate 0.87 ml/min.g kidney weight (p less than 0.001) and the secreted amount 2.01 and 2.38 ml/min.g kidney weight (p less than 0.05), respectively. We conclude that MAG-3 is predominantly excreted by tubular secretion and that the lower renal clearance of MAG-3 as compared with that of hippurate is a result both of a substantially decreased glomerular filtration and of a lower tubular secretion

  14. Renal scintigraphy in insulin-dependent diabetes mellitus: Early glomerular and urologic dysfunction

    International Nuclear Information System (INIS)

    Poirier, J.Y.; Moisan, A.; Le Cloirec, J.; Siemen, C.; Yaouanq, J.; Edan, G.; Herry, J.Y.

    1990-01-01

    Glomerular filtration rate (GFR) and renal plasma flow (RPF) were measured by intravenous injection of 99mTc-diethylenetriaminepentaacetic acid (DTPA) and 131I-Hippuran in 115 insulin-dependent diabetic patients with albumin excretion rates (AER) less than 200 micrograms/min, and in 45 normal subjects. Separate kidney function and urinary elimination were estimated by renography. GFR was increased in the diabetic patients (152 +/- 24 ml/min/1.73 m2 vs. 128 +/- 15) and correlated significantly with RPF (r = 0.5; p less than 10(-9)). No relationship was found between GFR and the duration of diabetes, blood glucose, HbA1c, or AER. Fifty patients were hyperfiltering with RPF and filtration fraction higher than those in the normofiltering group. Slow intrarenal or pyeloureteral elimination, either unilateral or bilateral, was observed in 3 controls and 60 diabetic subjects (24 hyperfiltering; 36 normofiltering) and did not disappear with the patient in the standing position. In these 60 patients, mean age, duration of diabetes, blood glucose, HbA1c, 24 h albumin excretion rate, and frequency of peripheral or autonomic neuropathy did not differ from patients with normal scintigraphy; GFR was lower in the group with slow elimination, but not significantly so. 99mTc-DTPA renal uptake was symmetric in all the controls; asymmetric renal uptake with asymmetric GFR was observed in 13 patients (7 hyperfiltering; 6 normofiltering) and often associated with slower elimination. No evidence for renal stenotic atheroma or parenchymatous disease was found on the angiopyleoureterography. The results suggest that incipient uropathy is a very common phenomenon that occurs irrespective of glomerular dysfunction

  15. Rat glomerular epithelial cells in culture. Parietal or visceral epithelial origin

    International Nuclear Information System (INIS)

    Norgaard, J.O.

    1987-01-01

    Isolated glomeruli from rats were explanted under standard culture conditions and outgrowths were studied by light and electron microscopy in order to identify the cells. Rat glomerular samples contained 20 to 30% structurally well-preserved encapsulated glomeruli which had a large rate of attachment to the substrate and very constantly gave rise to cellular outgrowth. In order to label cells from which outgrowth originated the glomerular incorporation of [ 3 H]thymidine was studied in the preattachment phase. By light and electron microscope autoradiograph it was demonstrated that label was located only over visceral and parietal epithelial cells during the first 3 days of culture. Incorporation of [ 3 H]thymidine was seen in mesangial cells after 5 days, i.e., after the glomeruli had attached to the culture vessels and the initial outgrowth had appeared. Consequently the first cells to grow out were of epithelial origin. Glomeruli were then incubated with [ 3 H]thymidine for the first 2 1/2 days of culture in order to label the epithelial cells, then were allowed to attach to the substrate and induce cell outgrowth. By light microscope autoradiography performed with the outgrowths in situ two types of cells with labeled nuclei were seen: (a) a small, polyhedral ciliated cell which grew in colonies where the cells were joined by junctional complexes (type I), and (b) a second very large, often multinucleated cell (type II). Based on the structural resemblance with their counterparts in situ and on comparisons with positively identified visceral epithelial cells in outgrowths from other species it is suggested that type I cells are derived from the parietal epithelium of Bowman's capsule and type II cells from the visceral epithelium

  16. The Application of Digital Pathology to Improve Accuracy in Glomerular Enumeration in Renal Biopsies.

    Directory of Open Access Journals (Sweden)

    Avi Z Rosenberg

    Full Text Available In renal biopsy reporting, quantitative measurements, such as glomerular number and percentage of globally sclerotic glomeruli, is central to diagnostic accuracy and prognosis. The aim of this study is to determine the number of glomeruli and percent globally sclerotic in renal biopsies by means of registration of serial tissue sections and manual enumeration, compared to the numbers in pathology reports from routine light microscopic assessment.We reviewed 277 biopsies from the Nephrotic Syndrome Study Network (NEPTUNE digital pathology repository, enumerating 9,379 glomeruli by means of whole slide imaging. Glomerular number and the percentage of globally sclerotic glomeruli are values routinely recorded in the official renal biopsy pathology report from the 25 participating centers. Two general trends in reporting were noted: total number per biopsy or average number per level/section. Both of these approaches were assessed for their accuracy in comparison to the analogous numbers of annotated glomeruli on WSI.The number of glomeruli annotated was consistently higher than those reported (p<0.001; this difference was proportional to the number of glomeruli. In contrast, percent globally sclerotic were similar when calculated on total glomeruli, but greater in FSGS when calculated on average number of glomeruli (p<0.01. The difference in percent globally sclerotic between annotated and those recorded in pathology reports was significant when global sclerosis is greater than 40%.Although glass slides were not available for direct comparison to whole slide image annotation, this study indicates that routine manual light microscopy assessment of number of glomeruli is inaccurate, and the magnitude of this error is proportional to the total number of glomeruli.

  17. Alternatives for the Bedside Schwartz Equation to Estimate Glomerular Filtration Rate in Children.

    Science.gov (United States)

    Pottel, Hans; Dubourg, Laurence; Goffin, Karolien; Delanaye, Pierre

    2018-01-01

    The bedside Schwartz equation has long been and still is the recommended equation to estimate glomerular filtration rate (GFR) in children. However, this equation is probably best suited to estimate GFR in children with chronic kidney disease (reduced GFR) but is not optimal for children with GFR >75 mL/min/1.73 m 2 . Moreover, the Schwartz equation requires the height of the child, information that is usually not available in the clinical laboratory. This makes automatic reporting of estimated glomerular filtration rate (eGFR) along with serum creatinine impossible. As the majority of children (even children referred to nephrology clinics) have GFR >75 mL/min/1.73 m 2 , it might be interesting to evaluate possible alternatives to the bedside Schwartz equation. The pediatric form of the Full Age Spectrum (FAS) equation offers an alternative to Schwartz, allowing automatic reporting of eGFR since height is not necessary. However, when height is involved in the FAS equation, the equation is essentially equal to the Schwartz equation for children, but there are large differences for adolescents. Combining standardized biomarkers increases the prediction performance of eGFR equations for children, reaching P10 ≈ 45% and P30 ≈ 90%. There are currently good and simple alternatives to the bedside Schwartz equation, but the more complex equations combining serum creatinine, serum cystatin C, and height show the highest accuracy and precision. Copyright © 2017 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

  18. IV injection of polystyrene beads for mouse model of sepsis causes severe glomerular injury.

    Science.gov (United States)

    Arima, Hajime; Hirate, Hiroyuki; Sugiura, Takeshi; Suzuki, Shugo; Takahashi, Satoru; Sobue, Kazuya

    2014-01-01

    Infusion fluids may be contaminated with different types of particulates that are a potential health hazard. Particulates larger than microvessels may cause an embolism by mechanical blockage and inflammation; however, it has been reported that particulates smaller than capillary diameter are relatively safe. Against such a background, one report showed that polystyrene beads smaller than capillary diameter decreased tissue perfusion in ischemia-reperfusion injury. This report suggested that polystyrene beads from 1.5- to 6-μm diameter (dia.) may have unfavorable effects after pretreatment. Here, we investigated whether injection of polystyrene beads (3- and 6-μm dia.) as an artificial contaminant of intravenous fluid after lipopolysaccharide (LPS) injection affected mortality and organ damage in mice. Mice were divided into four groups and injected: polystyrene beads only, LPS only, polystyrene beads 30 min after LPS, or saline. A survival study, histology, blood examination, and urine examination were performed. The survival rate after LPS and polystyrene bead (6-μm dia.) injection was significantly lower than that of the other three groups. In the kidney sections, injured glomeruli were significantly higher with LPS and polystyrene bead injection than that of the other three groups. LPS and polystyrene bead injection decreased the glomerular filtration rate and led to renal failure. Inflammatory reactions induced with LPS were not significantly different between with or without polystyrene beads. Polystyrene beads were found in urine after LPS and polystyrene bead injection. Injection of polystyrene beads after LPS injection enhanced glomerular structural injury and caused renal function injury in a mouse sepsis model.

  19. Zika Virus Infection of the Human Glomerular Cells: Implications for Viral Reservoirs and Renal Pathogenesis.

    Science.gov (United States)

    Alcendor, Donald J

    2017-07-15

    Zika virus (ZIKV) infection in the human renal compartment has not been reported. Several clinical reports have describe high-level persistent viral shedding in the urine of infected patients, but the associated mechanisms have not been explored until now. The current study examined cellular components of the glomerulus of the human kidney for ZIKV infectivity. I infected primary human podocytes, renal glomerular endothelial cells (GECs), and mesangial cells with ZIKV. Viral infectivity was analyzed by means of microscopy, immunofluorescence, real-time reverse-transcription polymerase chain reaction (RT-PCR), and quantitative RT-PCR (qRT-PCR), and the proinflammatory cytokines interleukin 1β, interferon β, and RANTES (regulated on activation of normal T cells expressed and secreted) were assessed using qRT-PCR. I show that glomerular podocytes, renal GECs, and mesangial cells are permissive for ZIKV infection. ZIKV infectivity was confirmed in all 3 cell types by means of immunofluorescence staining, RT-PCR, and qRT-PCR, and qRT-PCR analysis revealed increased transcriptional induction of interleukin 1β, interferon β, and RANTES in ZIKV-infected podocytes at 72 hours, compared with renal GECs and mesangial cells. The findings of this study support the notion that the glomerulus may serve as an amplification reservoir for ZIKV in the renal compartment. The impact of ZIKV infection in the human renal compartment is unknown and will require further study. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

  20. One-sample determination of glomerular filtration rate (GFR) in children. An evaluation based on 75 consecutive patients

    DEFF Research Database (Denmark)

    Henriksen, Ulrik Lütken; Kanstrup, Inge-Lis; Henriksen, Jens Henrik Sahl

    2013-01-01

    Abstract Background and aim. From a clinical point of view determination of glomerular filtration rate (clearance) is important. The aim of the present study was to compare the one-sample clearance to reference multiple-sample (51)Cr-EDTA clearance in consecutively referred children suspected...

  1. Effect of Calcineurin Inhibitor-Free Everolimus-Based Immunosuppressive Regimen on Albuminuria and Glomerular Filtration Rate after Heart Transplantation

    DEFF Research Database (Denmark)

    Nelson, Laerke M; Andreassen, Arne K; Andersson, Bert

    2017-01-01

    early CNI withdrawal in de novo HTx is unknown. METHODS: We tested if measured glomerular filtration rate (mGFR, by chrome-ethylenediaminetetraacetic acid clearance) was associated with urine albumin/creatinine ratio (UACR) post-HTx in a subgroup of patients included in the Scandinavian Heart Transplant...

  2. Renal uptake of dimercaptosuccinic acid and glomerular filtration rate in chronic nephropathy at angiotensin converting enzyme inhibition

    DEFF Research Database (Denmark)

    Kamper, A L; Thomsen, H S; Nielsen, S L

    1990-01-01

    Glomerular filtration rate (GFR) and renal uptake of dimercaptosuccinic acid (DMSA) were measured in 31 patients with progressive chronic nephropathy before and immediately after the start of treatment with angiotensin converting enzyme (ACE) inhibitor in order to control adverse effects on kidney...

  3. Simplified methods for assessment of renal function as the ratio of glomerular filtration rate to extracellular fluid volume

    DEFF Research Database (Denmark)

    Jødal, Lars; Brøchner-Mortensen, Jens

    2012-01-01

    Background: Instead of scaling glomerular filtration rate (GFR) to a body surface area of 1.73m2, it has been suggested to scale GFR to extracellular fluid volume (ECV). The ratio GFR/ECV has physiological meaning in that it indicates how often ‘that which is to be regulated’ (i.e. ECV) comes...

  4. Outcome Assessment of a Computer-Animated Model for Learning about the Regulation of Glomerular Filtration Rate

    Science.gov (United States)

    Gookin, Jody L.; McWhorter, Dan; Vaden, Shelly; Posner, Lysa

    2010-01-01

    The regulation of the glomerular filtration rate (GFR) is a particularly important and challenging concept for students to integrate into a memorable framework for building further knowledge and solving clinical problems. In this study, 76 first-year veterinary students and 19 veterinarians in clinical specialty training (house officers)…

  5. Plasma NGAL and glomerular filtration rate in cardiac transplant recipients treated with standard or reduced calcineurin inhibitor levels

    DEFF Research Database (Denmark)

    Gustafsson, Finn; Gude, Einar; Sigurdardottir, Vilborg

    2014-01-01

    AIM: Predictors of renal recovery following conversion from calcineurin inhibitor- to proliferation signal inhibitor-based therapy are lacking. We hypothesized that plasma NGAL (P-NGAL) could predict improvement in glomerular filtration rate (GFR) after conversion to everolimus. PATIENTS & METHODS...

  6. DISTRIBUTION OF GBM HEPARAN-SULFATE PROTEOGLYCAN CORE PROTEIN AND SIDE-CHAINS IN HUMAN GLOMERULAR-DISEASES

    NARCIS (Netherlands)

    VANDENBORN, J; VANDENHEUVEL, LPWJ; BAKKER, MAH; VEERKAMP, JH; ASSMANN, KJM; WEENING, JJ; BERDEN, JHM

    Using monoclonal antibodies (mAbs) recognizing either the core protein or the heparan sulfate (HS) side chain of human GBM heparan sulfate proteoglycan (HSPG), we investigated their glomerular distribution on cryostat sections of human kidney tissues. The study involved 95 biopsies comprising twelve

  7. Estimating glomerular filtration rate: Cockcroft-Gault and Modification of Diet in Renal Disease formulas compared to renal inulin clearance.

    NARCIS (Netherlands)

    Botev, R.; Mallie, J.P.; Couchoud, C.; Schuck, O.; Fauvel, J.P.; Wetzels, J.F.M.; Lee, N.; Santo, N.G. De; Cirillo, M.

    2009-01-01

    BACKGROUND AND OBJECTIVES: Evaluation of renal function by estimation of the glomerular filtration rate (GFR) is very important for the diagnosis and treatment of patients with chronic kidney disease (CKD). The Cockcroft-Gault (CG) and Modification of Diet in Renal Disease (MDRD) formulas are the

  8. Mutation in the key enzyme of sialic acid biosynthesis causes severe glomerular proteinuria and is rescued by N-acetylmannosamine.

    Science.gov (United States)

    Galeano, Belinda; Klootwijk, Riko; Manoli, Irini; Sun, MaoSen; Ciccone, Carla; Darvish, Daniel; Starost, Matthew F; Zerfas, Patricia M; Hoffmann, Victoria J; Hoogstraten-Miller, Shelley; Krasnewich, Donna M; Gahl, William A; Huizing, Marjan

    2007-06-01

    Mutations in the key enzyme of sialic acid biosynthesis, uridine diphospho-N-acetylglucosamine 2-epimerase/N-acetylmannosamine (ManNAc) kinase (GNE/MNK), result in hereditary inclusion body myopathy (HIBM), an adult-onset, progressive neuromuscular disorder. We created knockin mice harboring the M712T Gne/Mnk mutation. Homozygous mutant (Gne(M712T/M712T)) mice did not survive beyond P3. At P2, significantly decreased Gne-epimerase activity was observed in Gne(M712T/M712T) muscle, but no myopathic features were apparent. Rather, homozygous mutant mice had glomerular hematuria, proteinuria, and podocytopathy. Renal findings included segmental splitting of the glomerular basement membrane, effacement of podocyte foot processes, and reduced sialylation of the major podocyte sialoprotein, podocalyxin. ManNAc administration yielded survival beyond P3 in 43% of the Gne(M712T/M712T) pups. Survivors exhibited improved renal histology, increased sialylation of podocalyxin, and increased Gne/Mnk protein expression and Gne-epimerase activities. These findings establish this Gne(M712T/M712T) knockin mouse as what we believe to be the first genetic model of podocyte injury and segmental glomerular basement membrane splitting due to hyposialylation. The results also support evaluation of ManNAc as a treatment not only for HIBM but also for renal disorders involving proteinuria and hematuria due to podocytopathy and/or segmental splitting of the glomerular basement membrane.

  9. Early-Onset Diabetic E1-DN Mice Develop Albuminuria and Glomerular Injury Typical of Diabetic Nephropathy

    Directory of Open Access Journals (Sweden)

    Mervi E. Hyvönen

    2015-01-01

    Full Text Available The transgenic E1-DN mice express a kinase-negative epidermal growth factor receptor in their pancreatic islets and are diabetic from two weeks of age due to impaired postnatal growth of β-cell mass. Here, we characterize the development of hyperglycaemia-induced renal injury in the E1-DN mice. Homozygous mice showed increased albumin excretion rate (AER at the age of 10 weeks; the albuminuria increased over time and correlated with blood glucose. Morphometric analysis of PAS-stained histological sections and electron microscopy images revealed mesangial expansion in homozygous E1-DN mice, and glomerular sclerosis was observed in the most hyperglycaemic mice. The albuminuric homozygous mice developed also other structural changes in the glomeruli, including thickening of the glomerular basement membrane and widening of podocyte foot processes that are typical for diabetic nephropathy. Increased apoptosis of podocytes was identified as one mechanism contributing to glomerular injury. In addition, nephrin expression was reduced in the podocytes of albuminuric homozygous E1-DN mice. Tubular changes included altered epithelial cell morphology and increased proliferation. In conclusion, hyperglycaemic E1-DN mice develop albuminuria and glomerular and tubular injury typical of human diabetic nephropathy and can serve as a new model to study the mechanisms leading to the development of diabetic nephropathy.

  10. Detection of diffuse glomerular lesions in rats: II. Comparison of indium-111 cationic small macromolecules with technetium-99m DTPA

    International Nuclear Information System (INIS)

    McAfee, J.G.; Thomas, F.D.; Subramanian, G.; Schneider, R.D.; Lyons, B.; Roskopf, M.; Zapf-Longo, C.; Whaley, D.

    1986-01-01

    Dextrans with average molecular weights of 5000, 10,000, and 17,500 and inulin were rendered cationic by amination with 2-bromoethylamine hydrobromide. After limited coupling with DTPA cyclic dianhydride, they were labeled with 111In. A good correlation was found between their early renal uptake quantitated by camera-computer techniques and their renal clearance from multiple plasma samples in rats with glomerular damage induced by puromycin aminonucleoside and controls. However, there was poor correlation between the early renal uptake of these agents and the clearance of simultaneously injected [/sup 99m/Tc]DTPA. The 2-hr organ distribution and urinary excretion of these agents were compared with the corresponding values of DTPA. The differences in clearance between rats with glomerular damage and controls were greater with aminated dextran (mol wt 5000) than with DTPA, confirming previous work with infusions of nonradioactive charged dextrans and neutral inulin. The cationic dextrans appear to reflect the presence or absence of the normal anionic charge of the glomerular membrane as well as changes in filtration rate. Aminated inulin did not differentiate between controls and rats with glomerular disease any better than DTPA, probably because the number of amino groups conjugated was insufficient to produce the charge effect

  11. Preliminary Findings of Serum Creatinine and Estimated Glomerular Filtration Rate (eGFR) in Adolescents with Intellectual Disabilities

    Science.gov (United States)

    Lin, Jin-Ding; Lin, Lan-Ping; Hsieh, Molly; Lin, Pei-Ying

    2010-01-01

    The present study aimed to describe the kidney function profile--serum creatinine and estimated glomerular filtration rate (eGFR), and to examine the relationships of predisposing factors to abnormal serum creatinine in people with intellectual disabilities (ID). Data were collected by a cross-sectional study of 827 aged 15-18 years adolescents…

  12. Evidence for the existence of multiple heparan sulfate proteoglycans in the human glomerular basement membrane and mesangial matrix

    NARCIS (Netherlands)

    Groffen, Alexander J A; Hop, Frank W H; Tryggvason, Karl; Dijkman, Henri; Assmann, Karel J M; Veerkamp, Jacques H.; Monnens, Leo A H; Van Den Heuvel, Lambert P W J

    1997-01-01

    Heparan sulfate proteoglycans (HSPGs) are essential components of the glomerular basement membrane (GBM) carrying a strong anionic charge. A well- characterized extracellular HSPG is perlecan, ubiquitously expressed in basement membranes. A cDNA construct encoding domains I and II of human perlecan

  13. Glomerular and mitral-granule cell microcircuits coordinate temporal and spatial information processing in the olfactory bulb

    Directory of Open Access Journals (Sweden)

    Francesco Cavarretta

    2016-07-01

    Full Text Available The olfactory bulb processes inputs from olfactory receptor neurons (ORNs through two levels: the glomerular layer at the site of input, and the granule cell level at the site of output to the olfactory cortex. The sequence of action of these two levels has not yet been examined. We analyze this issue using a novel computational framework that is scaled up, in three-dimensions (3D, with realistic representations of the interactions between layers, activated by simulated natural odors, and constrained by experimental and theoretical analyses. We suggest that the postulated functions of glomerular circuits have as their primary role transforming a complex and disorganized input into a contrast-enhanced and normalized representation, but cannot provide for synchronization of the distributed glomerular outputs. By contrast, at the granule cell layer, the dendrodendritic interactions mediate temporal decorrelation, which we show is dependent on the preceding contrast enhancement by the glomerular layer. The results provide the first insights into the successive operations in the olfactory bulb, and demonstrate the significance of the modular organization around glomeruli. This layered organization is especially important for natural odor inputs, because they activate many overlapping glomeruli.

  14. Monitoring renal function in children with Fabry disease: comparisons of measured and creatinine-based estimated glomerular filtration rate

    NARCIS (Netherlands)

    Tøndel, Camilla; Ramaswami, Uma; Aakre, Kristin Moberg; Wijburg, Frits; Bouwman, Machtelt; Svarstad, Einar

    2010-01-01

    Studies on renal function in children with Fabry disease have mainly been done using estimated creatinine-based glomerular filtration rate (GFR). The aim of this study was to compare estimated creatinine-based GFR (eGFR) with measured GFR (mGFR) in children with Fabry disease and normal renal

  15. The impact of estimated glomerular filtration rate equations on chronic kidney disease staging in pediatric renal or heart transplant recipients

    NARCIS (Netherlands)

    A.B. Vroling (Aram Ben); E.M. Dorresteijn (Eiske); K. Cransberg (Karlien); Y.B. de Rijke (Yolanda)

    2016-01-01

    textabstractBackground: The aim of this study was to evaluate the performance of selected pediatric estimated glomerular filtration rate (eGFR) equations in relation to the clinical management of children after renal or heart transplantation or post-chemotherapy treatment. Methods: This study was a

  16. Enhancement of glomerular filtration rate and renal plasma flow by oral glucose load in well controlled insulin-dependent diabetics

    DEFF Research Database (Denmark)

    Sandahl Christiansen, J; Christensen, C K; Hermansen, K

    1986-01-01

    Glomerular filtration rate (GFR) and renal plasma flow (RPF) were measured in 27 patients with uncomplicated insulin-dependent diabetes (IDDM) before and after an oral glucose load of 1.1 g glucose/kg body wt. In the 18 patients showing near-normoglycaemia (blood glucose less than or equal to 8 m...

  17. MDRD or CKD-EPI for glomerular filtration rate estimation in living kidney donors

    Directory of Open Access Journals (Sweden)

    Carla Burballa

    2018-03-01

    Full Text Available Introduction: The evaluation of the measured Glomerular Filtration Rate (mGFR or estimated Glomerular Filtration Rate (eGFR is key in the proper assessment of the renal function of potential kidney donors. We aim to study the correlation between glomerular filtration rate estimation equations and the measured methods for determining renal function. Material and methods: We analyzed the relationship between baseline GFR values measured by Tc-99m-DTPA (diethylene-triamine-pentaacetate and those estimated by the four-variable Modification of Diet in Renal Disease (MDRD4 and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI equations in a series of living donors at our institution. Results: We included 64 donors (70.6% females; mean age 48.3 ± 11 years. Baseline creatinine was 0.8 ± 0.1 mg/dl and it was 1.1 ± 0.2 mg/dl one year after donation. The equations underestimated GFR when measured by Tc99m-DTPA (MDRD4 – 9.4 ± 25 ml/min, P < .05, and CKD-EPI – 4.4 ± 21 ml/min. The correlation between estimation equations and the measured method was superior for CKD-EPI (r = .41; P < .004 than for MDRD4 (r = .27; P < .05. eGFR decreased to 59.6 ± 11 (MDRD4 and 66.2 ± 14 ml/min (CKD-EPI one year after donation. This means a mean eGFR reduction of 28.2 ± 16.7 ml/min (MDRD4 and 27.31 ± 14.4 ml/min (CKD-EPI at one year. Conclusions: In our experience, CKD-EPI is the equation that better correlates with mGFR-Tc99m-DTPA when assessing renal function for donor screening purposes. Resumen: Introducción: El estudio del filtrado glomerular medido (FGm o del estimado (FGe es el eje de la evaluación adecuada de la función renal en la valoración de un potencial donante vivo renal. Nos planteamos estudiar la correlación entre las fórmulas de estimación del FG y los métodos de medición para

  18. Intestinal Barrier and Behavior.

    Science.gov (United States)

    Julio-Pieper, M; Bravo, J A

    2016-01-01

    The intestinal barrier function contributes to gut homeostasis by modulating absorption of water, electrolytes, and nutrients from the lumen into the circulation while restricting the passage of noxious luminal substances and microorganisms. Chronic conditions such as rheumatoid arthritis, inflammatory bowel disease, and celiac disease are associated to intestinal barrier dysfunction. Here, the hypothesis is that a leaky intestinal wall allowing for indiscriminate passage of intraluminal compounds to the vascular compartment could in turn lead to systemic inflammation. An increasing number of studies are now investigating the association between gut permeability and CNS disorders, under the premise that translocation of intestinal luminal contents could affect CNS function, either directly or indirectly. Still, it is unknown whether disruption of intestinal barrier is a causative agent or a consequence in these situations. Here, we discuss the latest evidence pointing to an association between increased gut permeability and disrupted behavioral responses. © 2016 Elsevier Inc. All rights reserved.

  19. Skin barrier in rosacea*

    Science.gov (United States)

    Addor, Flavia Alvim Sant'Anna

    2016-01-01

    Recent studies about the cutaneous barrier demonstrated consistent evidence that the stratum corneum is a metabolically active structure and also has adaptive functions, may play a regulatory role in the inflammatory response with activation of keratinocytes, angiogenesis and fibroplasia, whose intensity depends primarily on the intensity the stimulus. There are few studies investigating the abnormalities of the skin barrier in rosacea, but the existing data already show that there are changes resulting from inflammation, which can generate a vicious circle caused a prolongation of flare-ups and worsening of symptoms. This article aims to gather the most relevant literature data about the characteristics and effects of the state of the skin barrier in rosacea. PMID:26982780

  20. Health Barriers to Learning

    Directory of Open Access Journals (Sweden)

    Delaney Gracy

    2014-01-01

    Full Text Available This article summarizes the results from a 2013 online survey with 408 principals and assistant principals in New York City public elementary and middle schools. The survey assessed three primary areas: health issues in the school, health issues perceived as barriers to learning for affected students, and resources needed to address these barriers. Eighteen of the 22 health conditions listed in the survey were considered a moderate or serious issue within their schools by at least 10% of respondents. All 22 of the health issues were perceived as a barrier to learning by between 12% and 87% of the respondents. Representatives from schools that serve a higher percentage of low-income students reported significantly higher levels of concern about the extent of health issues and their impact on learning. Respondents most often said they need linkages with organizations that can provide additional services and resources at the school, especially for mental health.

  1. Glomerular diseases in the Military Hospital of Morocco: Review of a single centre renal biopsy database on adults

    Science.gov (United States)

    Aatif, T.; Maoujoud, O.; Montasser, D. I.; Benyahia, M.; Oualim, Z.

    2012-01-01

    Epidemiological studies provide useful information for clinical practice and investigations. This report aimed to determine glomerular diseases frequencies in a region of Morocco. All native renal biopsies (January 2000 to December 2007) on adults were reviewed, but only glomerular diseases were analyzed. The diagnosis of each case was based on histological, immunopathological and clinical features. We have performed 171 renal biopsies in 161 patients (101 males and 60 females), the mean age was (range) 40.4 ±15 years (16–72). Clinical indications that lead to renal biopsy were: nephrotic syndrome (60.3%), renal failure of unknown aetiology (31.6%), asymptomatic urinary abnormalities (6.2%) and nephritic syndrome(1.9%). Primary glomerular diseases were reported in 84 patients (52%). The most common histological lesion was minimal change disease (26%). Idiopathic membranous glomerulopathy was the second most common lesion (23%) followed by membranoproliferative glomerulonephritis (17%), IgA nephropathy (12%), focal and segmental glomerulosclerosis (9.4%) and crescentic glomerulonephritis (6%). Secondary glomerular diseases were reported in 53 patients (33%). Lupus nephritis was the secondary glomerular disease most frequent (45%) followed by amyloïdosis (19%), diabetic nephropathy (15%), and Good pasture's syndrome (7.6%). The most common complications of the procedure were pain at biopsy site in 4%, gross hematuria in 11.1%, perirenal hematoma in 5% and hematuria requiring nephrectomy in 0.6% patients. Minimal change disease was the most frequent primary glomerulopathy and lupus nephritis was the most frequent secondary glomerulopathy in our group. The reasons for these findings are unclear. This information is an important contribution to the understanding the prevalence of renal diseases in North Africa. PMID:23162268

  2. Crossing the Salt Barrier

    Indian Academy of Sciences (India)

    Fry. RIVER. To cross the salt barrier is, therefore, an obligatory part of every amphihaline fish cycle. Figure 2a. Life Cycle of. Salmon. Adult salmon migrate from sea towards the river. After reaching their hatching ground, the eggs are laid in the gravel. The spawned fishes are called kelts. Alevin is a stage from hatching to fry.

  3. Great Barrier Reef

    Science.gov (United States)

    2002-01-01

    A better than average view of the Great Barrier Reef was captured by SeaWiFS on a recent overpass. There is sunglint northeast of the reef and there appears to be some sort of filamentous bloom in the Capricorn Channel.

  4. Sound trapping and dredging barriers.

    Science.gov (United States)

    Wang, Xu; Wang, Xiaonan; Yu, Wuzhou; Jiang, Zaixiu; Mao, Dongxing

    2017-06-01

    When sound barriers are installed on both sides of a noise source, degradation in performance is observed. Barriers having negative-phase-gradient surfaces successfully eliminate this drawback by trapping sound energy in between the barriers. In contrast, barriers can also be designed to "dredge" the energy flux out. An extended model considering higher-order diffractions, which resulted from the interplay of the induced surface wave and barrier surface periodicity, is presented. It is found that the sound dredging barriers provide a remarkable enhancement over the trapping ones, and hence have the potential to be widely used in noise control engineering.

  5. Variability of glomerular filtration rate estimation equations in elderly Chinese patients with chronic kidney disease

    Directory of Open Access Journals (Sweden)

    Liu X

    2012-10-01

    Full Text Available Xun Liu,1,2,* Mu-hua Cheng,3,* Cheng-gang Shi,1 Cheng Wang,1 Cai-lian Cheng,1 Jin-xia Chen,1 Hua Tang,1 Zhu-jiang Chen,1 Zeng-chun Ye,1 Tan-qi Lou11Division of Nephrology, Department of Internal Medicine, The Third Affiliated Hospital of Sun Yet-sun University, Guangzhou, China; 2College of Biology Engineering, South China University of Technology, Guangzhou, China; 3Department of Nuclear Medicine, The Third Affiliated Hospital of Sun Yet-sun University, Guangzhou, China *These authors contributed equally to this paperBackground: Chronic kidney disease (CKD is recognized worldwide as a public health problem, and its prevalence increases as the population ages. However, the applicability of formulas for estimating the glomerular filtration rate (GFR based on serum creatinine (SC levels in elderly Chinese patients with CKD is limited.Materials and methods: Based on values obtained with the technetium-99m diethylenetriaminepentaacetic acid (99mTc-DTPA renal dynamic imaging method, 319 elderly Chinese patients with CKD were enrolled in this study. Serum creatinine was determined by the enzymatic method. The GFR was estimated using the Cockroft–Gault (CG equation, the Modification of Diet in Renal Disease (MDRD equations, the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI equation, the Jelliffe-1973 equation, and the Hull equation.Results: The median of difference ranged from −0.3–4.3 mL/min/1.73 m2. The interquartile range (IQR of differences ranged from 13.9–17.6 mL/min/1.73 m2. Accuracy with a deviation less than 15% ranged from 27.6%–32.9%. Accuracy with a deviation less than 30% ranged from 53.6%–57.7%. Accuracy with a deviation less than 50% ranged from 74.9%–81.5%. None of the equations had accuracy up to the 70% level with a deviation less than 30% from the standard glomerular filtration rate (sGFR. Bland–Altman analysis demonstrated that the mean difference ranged from −3.0–2.4 mL/min/1.73 m2. However, the

  6. Geophysical characterization of subsurface barriers

    International Nuclear Information System (INIS)

    Borns, D.J.

    1995-08-01

    An option for controlling contaminant migration from plumes and buried waste sites is to construct a subsurface barrier of a low-permeability material. The successful application of subsurface barriers requires processes to verify the emplacement and effectiveness of barrier and to monitor the performance of a barrier after emplacement. Non destructive and remote sensing techniques, such as geophysical methods, are possible technologies to address these needs. The changes in mechanical, hydrologic and chemical properties associated with the emplacement of an engineered barrier will affect geophysical properties such a seismic velocity, electrical conductivity, and dielectric constant. Also, the barrier, once emplaced and interacting with the in situ geologic system, may affect the paths along which electrical current flows in the subsurface. These changes in properties and processes facilitate the detection and monitoring of the barrier. The approaches to characterizing and monitoring engineered barriers can be divided between (1) methods that directly image the barrier using the contrasts in physical properties between the barrier and the host soil or rock and (2) methods that reflect flow processes around or through the barrier. For example, seismic methods that delineate the changes in density and stiffness associated with the barrier represents a direct imaging method. Electrical self potential methods and flow probes based on heat flow methods represent techniques that can delineate the flow path or flow processes around and through a barrier

  7. Should physicians always rely on estimated glomerular filtration rate without knowing the equation?

    Directory of Open Access Journals (Sweden)

    Fabbian F

    2017-08-01

    Full Text Available Fabio Fabbian, Dario Priori, Alfredo De Giorgi Department of Medical Sciences, Clinica Medica Unit, University Hospital St Anna, University of Ferrara, Ferrara, ItalyWe read with interest the paper written by Deskur-Smielecka et al1 who investigated the performance of three equations for valuating renal function in 174 patients, aged 78 years, with different cancer diagnosis. They used Cockcroft–Gault (C–G, Modification of Diet in Renal Disease (MDRD, and Berlin Initiative Study1 (BIS1 equations and found that there is a considerable disagreement between renal function estimation formulas. We also performed two studies evaluating different formulas for the calculation of glomerular filtration rate (GFR in patients with eating disorders2 and in those with type 2 diabetes mellitus (DM.3Authors’ replyEwa Deskur-Smielecka1,2 Aleksandra Kotlinska-Lemieszek1,2 Jerzy Chudek3,4 Katarzyna Wieczorowska-Tobis1,2The letter from Fabbian et al, in general, supports our findings concerning the disagreement between currently used equations for the estimation of glomerular filtration rate (GFR. We agree that disagreement in the estimation of kidney function was previously found by a number of authors. However, in our paper1 we describe this aspect in very specific population – geriatric, palliative care patients – with high prevalence of cachexia and substantial muscle mass loss. Our group has shown some similarities (low creatinine generation to the group of patients with anorexia nervosa and bulimia nervosa studied by Fabbian et al.2 However, it has to be stressed that patients with anorexia nervosa and bulimia nervosa were much younger, and therefore had much better, mostly normal kidney function. The second population analyzed by Fabbian et al3 – diabetic patients – also differ from out cohort, as they were better nourished. Regardless of these differences, the conclusions concerning the disagreement of different methods in the estimation of

  8. Glomerular and tubular dysfunction in children with congenital cyanotic heart disease: effect of palliative surgery.

    Science.gov (United States)

    Awad, Hesham; el-Safty, Ibrahim; Abdel-Gawad, Moustafa; el-Said, Salwa

    2003-03-01

    Nephropathy has long been recognized as a potential complication of congenital cyanotic heart disease (CCHD). The present study was undertaken to investigate some aspects of glomerular function by measuring urinary total protein, microalbumin, and tubular function by assessing urinary alpha-1-microglobulin. The structural integrity of the renal proximal tubules was also studied by measuring urinary activities of the brush-border enzyme leucine-aminopeptidase and the lysosomal enzyme -acetyl-beta-d-glucosaminidase. The levels of hematocrit (Hct) and oxygen saturation were also investigated as predisposing factors for renal impairment in CCHD. These investigations were done by recruiting 86 children who were grouped as follows: the control group (G1 ) consisted of 14 children (aged 4-12 years); the other 72 children with CCHD were divided according to age (ie, duration of cyanosis) into 4 equal groups, each containing 18 patients: G2 (age or = 1 year and or = 5 years and or = 10 years). In addition, 10 of the 72 patients underwent a palliative surgery and were included as G6 (regardless of age: 2 from G3, 4 from G4, and 4 from G5 ) to study the effect of the palliative surgery on the above-mentioned parameters. Results of the present work showed that with increasing duration of cyanosis (ie, on going from G2 to G5 ) among the studied children with CCHD, there was a significant elevation in the urinary excretion of the investigated functional and structural parameters of the glomeruli and proximal tubules compared with the control children. The data also showed a significant increase in Hct, whereas oxygen saturation was significantly decreased. Results of G6 after the palliative surgery demonstrated a significant decrease in the urinary excretion of the investigated parameters of the kidney, with a significant decrease in Hct and increase in oxygen saturation levels, compared with the results of the patients of this group before the palliative surgery. These results

  9. Automating and estimating glomerular filtration rate for dosing medications and staging chronic kidney disease

    Directory of Open Access Journals (Sweden)

    Trinkley KE

    2014-05-01

    Full Text Available Katy E Trinkley,1 S Michelle Nikels,2 Robert L Page II,1 Melanie S Joy11Skaggs School of Pharmacy and Pharmaceutical Sciences, 2School of Medicine, University of Colorado, Aurora, CO, USA Objective: The purpose of this paper is to serve as a review for primary care providers on the bedside methods for estimating glomerular filtration rate (GFR for dosing and chronic kidney disease (CKD staging and to discuss how automated health information technologies (HIT can enhance clinical documentation of staging and reduce medication errors in patients with CKD.Methods: A nonsystematic search of PubMed (through March 2013 was conducted to determine the optimal approach to estimate GFR for dosing and CKD staging and to identify examples of how automated HITs can improve health outcomes in patients with CKD. Papers known to the authors were included, as were scientific statements. Articles were chosen based on the judgment of the authors.Results: Drug-dosing decisions should be based on the method used in the published studies and package labeling that have been determined to be safe, which is most often the Cockcroft–Gault formula unadjusted for body weight. Although Modification of Diet in Renal Disease is more commonly used in practice for staging, the CKD–Epidemiology Collaboration (CKD–EPI equation is the most accurate formula for estimating the CKD staging, especially at higher GFR values. Automated HITs offer a solution to the complexity of determining which equation to use for a given clinical scenario. HITs can educate providers on which formula to use and how to apply the formula in a given clinical situation, ultimately improving appropriate medication and medical management in CKD patients.Conclusion: Appropriate estimation of GFR is key to optimal health outcomes. HITs assist clinicians in both choosing the most appropriate GFR estimation formula and in applying the results of the GFR estimation in practice. Key limitations of the

  10. Efectos de la circulación extracorpórea sobre el filtrado glomerular en la cirugía cardiovascular pediátrica Effects of extracorporeal circulation on glomerular filtration in pediatric cardiovascular surgery

    OpenAIRE

    Abel Facenda; Antolín Romero; Junior M Lima; Cruz M Contreras; Heilyn del Valle Montero; Manuel G Lima Montero

    2011-01-01

    Objetivo: conocer como afecta la circulación extracorpórea la función renal tomando como marcador la alteración del filtrado glomerular. Material y método: se realizó un estudio prospectivo, analítico y observacional en 63 pacientes pediátricos sometidos a cirugía cardiaca electiva con circulación extracorpórea en el Cardiocentro Pediátrico «William Soler» entre octubre de 2009 y abril de 2010. Se calcularon las variaciones del filtrado glomerular durante la circulación extracorpórea por el m...

  11. Apoplastic Diffusion Barriers in Arabidopsis

    Science.gov (United States)

    Schreiber, Lukas; Franke, Rochus Benni; Geldner, Niko; Reina-Pinto, José J.; Kunst, Ljerka

    2013-01-01

    During the development of Arabidopsis and other land plants, diffusion barriers are formed in the apoplast of specialized tissues within a variety of plant organs. While the cuticle of the epidermis is the primary diffusion barrier in the shoot, the Casparian strips and suberin lamellae of the endodermis and the periderm represent the diffusion barriers in the root. Different classes of molecules contribute to the formation of extracellular diffusion barriers in an organ- and tissue-specific manner. Cutin and wax are the major components of the cuticle, lignin forms the early Casparian strip, and suberin is deposited in the stage II endodermis and the periderm. The current status of our understanding of the relationships between the chemical structure, ultrastructure and physiological functions of plant diffusion barriers is discussed. Specific aspects of the synthesis of diffusion barrier components and protocols that can be used for the assessment of barrier function and important barrier properties are also presented. PMID:24465172

  12. Performance of engineered barriers

    International Nuclear Information System (INIS)

    Rajaram, V.; Dean, P.V.; McLellan, S.A.

    1997-01-01

    Engineered barriers, both vertical and horizontal, have been used to isolate hazardous wastes from contact, precipitation, surface water and groundwater. The primary objective of this study was to determine the performance of subsurface barriers installed throughout the U.S. over the past 20 years to contain hazardous wastes. Evaluation of Resource Conservation and Recovery Act (RCRA) Subtitle C or equivalent caps was a secondary objective. A nationwide search was launched to select hazardous waste sites at which vertical barrier walls and/or caps had been used as the containment method. None of the sites selected had an engineered floor. From an initial list of 130 sites, 34 sites were selected on the basis of availability of monitoring data for detailed analysis of actual field performance. This paper will briefly discuss preliminary findings regarding the design, construction quality assurance/construction quality control (CQA/CQC), and monitoring at the 34 sites. In addition, the short-term performance of these sites (less than 5 years) is presented since very little long-term performance data was available

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

    International Nuclear Information System (INIS)

    Henriksen, J.H.; Broechner-Mortensen, J.; Malchow-Moeller, A.; Schlichting, P.

    1980-01-01

    The total plasma (Clsub(t)) and the renal plasma (Clsub(r)) clearances of [ 51 Cr]EDTA were determined simultaneously in nine patients with ascites due to liver cirrhosis. Clsub(t) (mean 78 ml/min, range 34-115 ml/min) was significantly higher than Clsub(r) (mean 52 ml/min, range 13-96 ml/min, P 51 Cr]EDTA increased throughout the investigation period (5 h). The results suggested that [ 51 Cr]EDTA equilibrates slowly with the peritoneal space which indicates that Clsub(t) will over-estimate the glomerular filtration rate by approximately 20 ml/min in patients with ascites. To assess glomerular filtration rate in presence of ascites, the renal plasma clearance of [ 51 Cr]EDTA should be used instead of the total plasma clearance. (author)

  14. Glomerular Protein Levels of Matrix Metalloproteinase-1 and Tissue Inhibitor of Metalloproteinase-1 Are Lower in Diabetic Subjects

    Science.gov (United States)

    Cornish, Toby C.; Bagnasco, Serena M.; Macgregor, Anne M.; Lu, Jie; Selvin, Elizabeth; Halushka, Marc K.

    2009-01-01

    Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) regulate extracellular matrix turnover throughout the body, including in renal glomeruli. We investigated protein levels of multiple MMPs (MMP-1, MMP-2, MMP-3, and MMP-9) and TIMP-1 in glomeruli and investigated whether disease phenotypes were associated with levels of these proteins. Renal cortex was collected from 100 adult autopsy subjects arrayed across 17 tissue microarrays. Immunohistochemical staining intensity for each MMP and TIMP-1 was determined using quantitative color deconvolution techniques. We observed significantly decreased glomerular MMP-1 and TIMP-1 staining in subjects with diabetes, hypertension, and an estimated glomerular filtration rate contains online supplemental material at http://www.jhc.org. Please visit this article online to view these materials. (J Histochem Cytochem 57:995–1001, 2009) PMID:19506087

  15. The giraffe kidney tolerates high arterial blood pressure by high renal interstitial pressure and low glomerular filtration rate

    DEFF Research Database (Denmark)

    Damkjær, Mads; Wang, T; Brøndum, E

    2015-01-01

    adaption in the giraffe kidney allows normal for size renal haemodynamics and glomerular filtration rate (GFR) despite a MAP double that of other mammals. METHODS: Fourteen anaesthetized giraffes were instrumented with vascular and bladder catheters to measure glomerular filtration rate (GFR) and effective......BACKGROUND: The tallest animal on earth, the giraffe (Giraffa camelopardalis) is endowed with a mean arterial blood pressure (MAP) twice that of other mammals. The kidneys reside at heart level and show no sign of hypertension-related damage. We hypothesized that a species-specific evolutionary...... renal plasma flow (ERPF). Renal interstitial hydrostatic pressure (RIHP) was assessed by inserting a needle into the medullary parenchyma. Doppler ultrasound measurements provided renal artery resistive index (RI). Hormone concentrations as well as biomechanical, structural and histological...

  16. Radioisotopic measurement of glomerular filtration rate in severe chronic renal failure

    International Nuclear Information System (INIS)

    LaFrance, N.D.; Drew, H.H.; Walser, M.

    1988-01-01

    In order to determine the best method for routine measurement of glomerular filtration rate (GFR) in severe renal failure, we compared simultaneously the urinary clearances of [/sup 99m/Tc] diethylenetriaminepentaacetic acid (DTPA) (UD), [ 125 I]iothalamate (UI), 24-hr creatinine clearance (UC) and plasma clearance of [/sup 99m/Tc]DTPA (PD), based on three plasma samples. In 60 studies in 22 patients with serum creatinine values of 2 to 8 mg/dl, UD and UI were almost identical: UD = 0.358 +/- 0.976 UI +/- 0.87 ml/min, r = 0.990. However, PD overestimated UD by a large and variable extent: PD = 11.3 +/- 0.843 UD +/- 5.5 ml/min, r = 0.694, and was inconsistent in sequential measurements in individual patients. UC also overestimated urinary isotope clearance: UC = 4.2 + 0.95 UI +/- 3.9 ml/min, r = 0.865. Sequential measurements of GFR in five patients with severe but stable renal failure (mean GFR 5.9 ml/min) showed an average standard deviation of only 0.83 ml/min. Thus both UD and UI appear to be reliable and precise measures of GFR in severe renal failure

  17. Simplified estimation of glomerular filtration rate and effective renal plasma flow

    International Nuclear Information System (INIS)

    Smart, R.; Trew, P.; Burke, J.; Lyons, N.

    1981-01-01

    A method is described for the determination of GFR and ERPF using a combined injection of 51 Cr-EDTA and 125 I-iodohippurate. Plasma samples obtained at 60 min and 150 min after administration were used to determine a flow rate F assuming a monoexponential clearance of the tracers. Empirical relationships were found between F and the true glomerular filtration rate and effective renal plasma flow determined from multiple sampling and multi-exponential analysis of the clearance curves. The method was shown to be superior to previously published methods involving one or two samples. GFR was calculated with a standard deviation (SD) of only 3.3 ml/min when compared to the multiple sample technique (the reference method), whereas the best estimate from a single sample had a SD of 6.3 ml/min. An improvement in accuracy of ERPF estimation was achieved for values of flow of less than 200 ml/min when the SD was only 9.3 ml/min. (orig./MG)

  18. Improving precision of glomerular filtration rate estimating model by ensemble learning

    Directory of Open Access Journals (Sweden)

    Xun Liu

    2017-11-01

    Full Text Available Abstract Background Accurate assessment of kidney function is clinically important, but estimates of glomerular filtration rate (GFR by regression are imprecise. Methods We hypothesized that ensemble learning could improve precision. A total of 1419 participants were enrolled, with 1002 in the development dataset and 417 in the external validation dataset. GFR was independently estimated from age, sex and serum creatinine using an artificial neural network (ANN, support vector machine (SVM, regression, and ensemble learning. GFR was measured by 99mTc-DTPA renal dynamic imaging calibrated with dual plasma sample 99mTc-DTPA GFR. Results Mean measured GFRs were 70.0 ml/min/1.73 m2 in the developmental and 53.4 ml/min/1.73 m2 in the external validation cohorts. In the external validation cohort, precision was better in the ensemble model of the ANN, SVM and regression equation (IQR = 13.5 ml/min/1.73 m2 than in the new regression model (IQR = 14.0 ml/min/1.73 m2, P  0.05 for all comparisons of the new regression equation and the other new models. Conclusions An ensemble learning model including three variables, the average ANN, SVM, and regression equation values, was more precise than the new regression model. A more complex ensemble learning strategy may further improve GFR estimates.

  19. [Change in glomerular filtration rate in hypertensive patients in Vitória-ES].

    Science.gov (United States)

    Passigatti, Cynthia Perin; Molina, Maria Del Carmen; Cade, Nágela Valadão

    2014-01-01

    As monitoring of renal function, it is used the estimation of glomerular filtration rate (GFR). This study aimed to estimate the GFR by means of the Cockcroft-Gault equation in hypertensive patients in the Municipality of Vitoria-ES. It is a transversal study of secondary data with 754 hypertensive patients attended in health facilities in 2009. For statistical analysis, there has been used the chi-square test. The female sex, overweight and uncontrolled blood pressure predominated. The average age was 58.18 years (± 13.52) and the serum creatinine (SCr) 0.81 mg / dl (± 0.28). The prevalence of reduced GFR was 19% when from 30 to 59 ml/min and 1.6% when from 29 to 15 ml/min. The prevalence of reduced GFR was 15 times higher in the elderly, 4.93 times higher in those with elevated SCr, 2.19 times in low-weight hypertensives and 1.6 times more prevalent in men. The study showed the importance of monitoring renal function with a view to early intervention and postponement of kidney function loss in hypertensive patients.

  20. Glomerular filtration rate and functional decline in an acute geriatric unit

    Directory of Open Access Journals (Sweden)

    Ocampo Chaparro, José Mauricio

    2018-01-01

    Full Text Available Introduction: Low estimated Glomerular filtration rate (eGFR is associated with functional decline. Little is known on that association in hospitalized elderly. Objective: Determine if low eGFR is associated with functional decline. Methods: Prospective cohort study that included 1826 patients 60 years and older hospitalized in a Geriatric Acute Unit, admitted between January 2012 and August 2015. The outcome was functional status assessed four times by the Barthel Index (BI. Kidney function was estimated by MDRD-4 IDMS and was grouped into four categories according to eGFR (normal ≥90, mild 60-89, moderate 59-30, severe <30. Multivariate logistic regression models and GLIMMIX procedure for longitudinal analyzes were used. Results: Mean age was 82.3±7.2 years, 51 % were women. In multivariate logistic regression, a BI≤60 at admission was associated with age ≥80, female gender, high comorbidity, social deterioration, hypoalbuminemia, anemia, MMSE<19, while the presence of mild or moderate renal failure reduced this risk. In the longitudinal analysis, lower total BI at follow-up was associated with age ≥80, female gender, social deterioration, hospital stay ≥15 days, high comorbidity, hypoalbuminemia, MMSE<19. The presence of mild, moderate or severe renal impairment was associated with higher BI over time. Conclusions: A low eGFR was associated with lower risk for functional decline at admission and overtime. These findings differ from previous reports in the literature.

  1. Rac1 in podocytes promotes glomerular repair and limits the formation of sclerosis.

    Science.gov (United States)

    Asao, Rin; Seki, Takuto; Takagi, Miyuki; Yamada, Hiroyuki; Kodama, Fumiko; Hosoe-Nagai, Yoshiko; Tanaka, Eriko; Trejo, Juan Alejandro Oliva; Yamamoto-Nonaka, Kanae; Sasaki, Yu; Hidaka, Teruo; Ueno, Takashi; Yanagita, Motoko; Suzuki, Yusuke; Tomino, Yasuhiko; Asanuma, Katsuhiko

    2018-03-22

    Rac1, a Rho family member, is ubiquitously expressed and participates in various biological processes. Rac1 expression is induced early in podocyte injury, but its role in repair is unclear. To investigate the role of Rac1 expression in podocytes under pathological conditions, we used podocyte-specific Rac1 conditional knock-out (cKO) mice administered adriamycin (ADR), which causes nephrosis and glomerulosclerosis. Larger areas of detached podocytes, more adhesion of the GBM to Bowman's capsule, and a higher ratio of sclerotic glomeruli were observed in Rac1 cKO mice than in control mice, whereas no differences were observed in glomerular podocyte numbers in both groups after ADR treatment. The mammalian target of rapamycin (mTOR) pathway, which regulates the cell size, was more strongly suppressed in the podocytes of Rac1 cKO mice than in those of control mice under pathological conditions. In accordance with this result, the volumes of podocytes in Rac1 cKO mice were significantly reduced compared with those of control mice. Experiments using in vitro ADR-administered Rac1 knockdown podocytes also supported that a reduction in Rac1 suppressed mTOR activity in injured podocytes. Taken together, these data indicate that Rac1-associated mTOR activation in podocytes plays an important role in preventing the kidneys from developing glomerulosclerosis.

  2. Tubulo-glomerular feedback response: enhancement in adult spontaneously hypertensive rats and effects of anaesthetics

    DEFF Research Database (Denmark)

    Leyssac, P P; Holstein-Rathlou, N H

    1989-01-01

    Open-loop tubulo-glomerular feedback (TGF) responses were measured in halothane anaesthetized spontaneously hypertensive rats (SHR), in normotensive Wistar Kyoto (WKY) and Sprague-Dawley rats (SPRD), and in inactin anaesthetized SPRD. Proximal intratubular free flow pressures (FFP) (13.8-14.7 mm Hg......) and stop-flow pressures (40.0-42.4 mm Hg) were similar in the four groups, but systemic arterial pressure was significantly lower in WKY, and significantly higher in SHR than in SPRD. The turning point (Tp) of the feedback curve was 9.87 nl/min in SHR, significantly lower than the 13.04 nl/min found in WKY...... anaesthetized control group of SPRD, the feedback response was lower, and the feedback curve was displaced to the right with the Tp at 15.9 nl/min, significantly higher than in the control group (p less than 0.001). Although the steady state level also was reached within 2 min, the clearly biphasic pattern...

  3. Beta thalassemia major: The effect of age on glomerular filtration rate

    Directory of Open Access Journals (Sweden)

    Majid Malaki

    2011-01-01

    Full Text Available Thalassemia is a common hereditary hemoglobinopathy disorder that affects many organs in the body. Estimation of kidney function is important, as it is the vital organ that plays the major role in the elimination of accumulated iron as well as the chelating drugs that have to be used as therapy. Sixty- three patients aged 1-29 years, with a mean ± SD of 14 ± 6.7 years, affected with beta- thalassemia major in Tabriz Children′s Hospital were evaluated for their renal function on the basis of their age, serum iron, serum ferritin and serum creatinine levels along with two methods of estimating glomerular filtration rate (GFR; by Schwartz method for those under 18 years old and using Modification of Diet in Renal Disease (MDRD formula for those who were 18 years and above. Elevation of serum creatinine denoting renal dysfunction was not seen in our patients, but hyperfiltration was a common finding. An increasing GFR was observed, which corresponded to age, but no relationships were seen between serum iron, serum ferritin, regular blood transfusion, chelating therapy to GFR.

  4. Transcutaneous measurement of glomerular filtration rate in small rodents: through the skin for the win?

    Science.gov (United States)

    Ellery, Stacey J; Cai, Xiaochu; Walker, David D; Dickinson, Hayley; Kett, Michelle M

    2015-03-01

    Rodent models of renal physiology and pathology are crucial to our understanding of the molecular, histological and functional sequelae that contribute to kidney diseases. One of the most important measures of renal function is glomerular filtration rate (GFR). While the accurate determination of GFR is pivotal to understanding the progression of disease and/or the benefits of treatment strategies, in rodents the conventional methods for assessment of GFR are inconvenient and cumbersome, not the least because they involve stress and often anaesthesia. The legitimacy of assay-based assessment of plasma and urine markers of GFR in mice has also been heavily scrutinized for their insensitivity to minor declines in GFR and inaccurate detection of renal biomarkers. While infusion-based clearance methods of GFR assessment are thus the gold standard in terms of accuracy, they are limited by the fact that they are primarily non-recovery procedures. This presents a dilemma when trying to document the progression of renal disease, as these measures cannot be taken in the same experimental subject. Here we review a technique of transcutaneous measurement of fluorescein isothiocyanate-labelled sinistrin to calculate GFR in small rodents, using a non-invasive clearance device (NIC-Kidney Device). This is a recently validated non-invasive technique for measuring GFR in small rodents that allows for the real-time measurement of GFR in conscious animals, without the need for plasma and urine assays. © 2014 Asian Pacific Society of Nephrology.

  5. Chronic changes of hematocrit value alter blood pressure and glomerular filtration in spontaneously hypertensive rats

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    Milanović S.

    2012-01-01

    Full Text Available Many studies in hypertensive humans and animals have shown that increased blood viscosity is in direct relation with essential hypertension. The aim of our studies was to investigate the effects of chronic hematocrit value changes on arterial blood pressure and kidney function in genetically induced hypertension. To this end, we studied the effects of several interventions, designed to increase/decrease hematocrit, on hemodynamic parameters, vascular reactivity, glomerular filtration and renal function curve in spontaneously hypertensive rats (SHR. Results of our study show that chronic hematocrit value elevation increases blood pressure and peripheral vascular resistance in SHR. On the other hand, chronic hematocrit lowering elucidates blood pressure and peripheral vascular resistance decrease followed by cardiac output rising. Both hematocrit value changes significantly reduce vasodilatory vascular response. Hematocrit lowering induces acute renal failure. Sodium excretion is shifted to higher blood pressure values in high hematocrit value animals and opposite - lower blood pressure values in low hematocrit value animals. Repeated transfusions develop salt sensitive malignant hypertension in SHR. Further studies are necessary to evaluate the degree of kidney damage after chronic hematocrit value changes in SHR.

  6. Prediction of hospital mortality by changes in the estimated glomerular filtration rate (eGFR).

    LENUS (Irish Health Repository)

    Berzan, E

    2015-03-01

    Deterioration of physiological or laboratory variables may provide important prognostic information. We have studied whether a change in estimated glomerular filtration rate (eGFR) value calculated using the (Modification of Diet in Renal Disease (MDRD) formula) over the hospital admission, would have predictive value. An analysis was performed on all emergency medical hospital episodes (N = 61964) admitted between 1 January 2002 and 31 December 2011. A stepwise logistic regression model examined the relationship between mortality and change in renal function from admission to discharge. The fully adjusted Odds Ratios (OR) for 5 classes of GFR deterioration showed a stepwise increased risk of 30-day death with OR\\'s of 1.42 (95% CI: 1.20, 1.68), 1.59 (1.27, 1.99), 2.71 (2.24, 3.27), 5.56 (4.54, 6.81) and 11.9 (9.0, 15.6) respectively. The change in eGFR during a clinical episode, following an emergency medical admission, powerfully predicts the outcome.

  7. Albuminuria and reduced glomerular filtration rate for predicting the renal outcomes in type 2 diabetic patients.

    Science.gov (United States)

    Tanaka, Nobue; Babazono, Tetsuya; Takagi, Michino; Yoshida, Naoshi; Toya, Kiwako; Nyumura, Izumi; Hanai, Ko; Uchigata, Yasuko

    2015-08-01

    The first clinical manifestation of diabetic kidney disease is usually the development of microalbuminuria. However, recent studies have focused on diabetic patients with reduced glomerular filtration rate (GFR) without albuminuria. To evaluate the association of albuminuria and GFR with renal outcomes, we performed an observational study. A total of 3231 type 2 diabetic patients were included in this study between 2003 and 2005. There were 1249 women and the mean age was 59 ± 12 years. The renal endpoints were defined as the initiation of renal replacement therapy (RRT) or 50% reduction from the baseline of estimated GFR (eGFR). At baseline, 669 (20.7%) patients had eGFR albuminuria. During the mean follow-up period of 5.9 ± 1.6 years, 107 patients initiated RRT. A 50% reduction of eGFR from the baseline value was found in 279 patients. None of the normoalbuminuric subjects with or without reduced eGFR required RRT during the observational period (P Albuminuria was a significant predictor for the evaluated renal endpoints, but the impact of eGFR is likely to be less than that of albuminuria. © 2015 Asian Pacific Society of Nephrology.

  8. Protective effects of antioxidants on high Glucose-induced malfunctions in human glomerular mesangial cells

    Directory of Open Access Journals (Sweden)

    Hosseini R

    2000-08-01

    Full Text Available Altered functions of mesangial cells induced by high glucose concentrations are thought to play an important role in the pathogenesis of diabetic nephropathy. We therefore investigated the effect of high glucose (39.2 mM alone and in combination with taurine (500 µM or vitamin E (100 µM in serum free medium (RPMI 1640 on the proliferative growth response and turnover of type IV collagen by human glomerular mesangial cells (GMC. The results showed that the high glucose level decreases the proliferation of the GMC which is reversed by taurine and vitamin E. In order to control the osmotic effects of high glucose, the GMC were also cultured in the presence of manitol. Manitol had no effect on the proliferation of GMC. Furthermore, the results showed that addition of vitamin E or taurine to media containing high glucose could reverse and normalize the collagen turn-over by the cultured mesangial cells. These results suggest that taurie and vitamin E may function as endogenous agents in the kidney to limit the development of glomerulosclerosis in diabetic renal disease.

  9. Age-dependent reference intervals for estimated and measured glomerular filtration rate.

    Science.gov (United States)

    Pottel, Hans; Delanaye, Pierre; Weekers, Laurent; Selistre, Luciano; Goffin, Karolien; Gheysens, Olivier; Dubourg, Laurence

    2017-08-01

    Defining mean and reference intervals for glomerular filtration rate (GFR) has been the subject of only a limited number of studies and review articles, with contradicting statements about the mean. Normal measured GFR (mGFR) values of ∼120-130 mL/min/1.73 m 2 have long been the referenced values for young adults but seem to be too high according to recent studies. Reference intervals are difficult to define because of the age decline of GFR, which is also observed in healthy subjects. Little data are available for subjects >70 years of age. Based on the reference intervals for serum creatinine (SCr) and the recently published full-age spectrum (FAS) equation, we define simple age-dependent equations for the reference limits of GFR. The mGFR of 633 living potential kidney donors was used to validate the new formulae that define the reference interval. The reference limits for estimated GFR (eGFR), calculated by entering the reference limits for SCr into the FAS equation closely correspond with published reference limits for mGFR. Of the mGFRs of potential living kidney donors, 97.2% lie between the newly defined reference limits for GFR. SCr reference limits may serve to define age-dependent reference limits for eGFR and mGFR.

  10. Measurement of single-kidney glomerular filtration function from magnetic resonance perfusion renography

    Energy Technology Data Exchange (ETDEWEB)

    Zeng, Meiying; Cheng, Yingsheng [Department of Radiology, Shanghai Jiao Tong University Affiliated Sixth People' s Hospital, Shanghai 200233 (China); Zhao, Binghui, E-mail: binghuizhao@163.com [Department of Radiology, Shanghai Tenth People' s Hospital, Tongji University, Shanghai 200072 (China)

    2015-08-15

    Highlights: • MRPR monitors the transit of contrast material through nephron. • MRPR could reveal renal physiological characteristics in quality and quantity. • This review outlines the basics and future challenges of DCE MRPR. - Abstract: Glomerular filtration rate (GFR) describes the flow rate of filtered fluid through the kidney, and is considered to be the reference standard in the evaluation of renal function. There are many ways to test the GFR clinically, such as serum creatinine concentration, blood urea nitrogen and SPECT renography, however, they’re all not a good standard to evaluate the early damage of renal function. In recent years, the improvement of MRI hardware and software makes it possible to reveal physiological characteristics such as renal blood flow or GFR by dynamic contrast enhancement magnetic resonance perfusion renography (DEC MRPR). MRPR is a method used to monitor the transit of contrast material, typically a gadolinium chelate, through the renal cortex, the medulla, and the collecting system. This review outlines the basics of DCE MRPR included acquisition of dynamic MR perfusion imaging, calculation of the contrast concentration from signal intensity and compartment models, and some challenges of MRPR method faced in prospective clinical application.

  11. Characterization of growth, glomerular number, and tubular proteins in the developing rhesus monkey kidney.

    Science.gov (United States)

    Batchelder, Cynthia A; Keyser, Jennifer L; Lee, C Chang I; Tarantal, Alice F

    2013-11-01

    An essential step in the translation of cell-based therapies for kidney repair involves preclinical studies in relevant animal models. Regenerative therapies in children with congenital kidney disease may provide benefit, but limited quantitative data on normal development is available to aid in identifying efficient protocols for repair. Nonhuman primates share many developmental similarities with humans and provide an important translational model for understanding nephrogenesis and morphological changes across gestation. These studies assessed monkey kidney size and weight during development and utilized stereological methods to quantitate total number of glomeruli. Immunohistochemical methods were included to identify patterns of expression of tubular proteins including Aquaporin-1 (AQP1), AQP2, Calbindin, E-Cadherin, and Uromodulin. Results have shown that glomerular number increased linearly with kidney weight, from 1.1 × 10(3) in the late first trimester to 3.5 × 10(5) near term (P kidney ontogeny in rhesus monkeys and further support the importance of this model for human kidney development. Copyright © 2013 Wiley Periodicals, Inc.

  12. Effect of diabetes on in vivo metabolism of [35S]-labeled glomerular basement membrane

    International Nuclear Information System (INIS)

    Cohen, M.P.; Surma, M.L.

    1984-01-01

    Glomerular basement membrane (GBM) was labeled in vivo by the injection of tracer amounts of [ 35 S]-sulfate into normal and streptozotocin-diabetic rats. The biosynthesis and turnover of sulfated glycosaminoglycans in the GBM was determined from the specific activity of [ 35 S] after pronase digestion of basement membranes purified from glomeruli isolated 1-7 days after injection. Peak radiolabeling of both normal and diabetic GBM occurred 24 h after injection and, when corrected for differences in serum sulfate specific activities, was less in diabetic than in normal samples. The specific activity of GBM sulfate, expressed as cpm/microgram uronic acid, progressively diminished over the ensuing period of study in both normal and diabetic samples. The rate of decrease in specific activity of [ 35 S]-labeled GBM was not significantly different in diabetic preparations compared with that in normal controls. The findings are compatible with diminished sulfation and/or production but normal turnover of glycosaminoglycans in the renal GBM in experimental diabetes

  13. Association of Glomerular Filtration Rate with Inflammation in Polycystic Ovary Syndrome

    Directory of Open Access Journals (Sweden)

    Ilay Ozturk Gozukara

    2015-07-01

    Full Text Available Background: We aimed to estimate the glomerular filtration rate (GFR in women with polycystic ovary syndrome (PCOS and to determine the relationship between GFR with C-reactive protein (CRP and uric acid. Materials and Methods: In this cross-sectional study, one-hundred and forty PCOS women and 60 healthy subjects were evaluated. The study was carried out at Endocrinology Outpatient Clinic, Erzurum Training and Research Hospital, Erzurum, Turkey, from December 2010 to January 2011. GFRs were estimated by Modification of Diet in Renal Disease (MDRD formula. CRP, urinary albumin excretion (UAE and uric acid levels were also measured. Results: GFRs were significantly higher in PCOS group than control (135.24 ± 25.62 vs. 114.92 ± 24.07 ml/min per 1.73 m2. CRP levels were significantly higher in PCOS patients (4.4 ± 3.4 vs. 2.12 ± 1.5 mg/l. The PCOS group had significantly higher serum uric acid levels (4.36 ± 1.3 mg/dl vs. 3.2 ± 0.73 mg/dl. There was also significantly higher proteinuria level in PCOS patients. Conclusion: Even though PCOS patients had higher GFR, serum uric acid and UAE values than control patients, the renal function was within normal limits. Increased GFR in PCOS women positively correlates with elevated serum CRP and uric acid.

  14. Paraffin-based immunohistochemistry in the evaluation of glomerular diseases in renal biopsies

    International Nuclear Information System (INIS)

    Rathore, M.U.; Khadim, M.T.; Atique, M.

    2012-01-01

    Objective: To determine sensitivity and specificity of paraffin-based immunohistochemistry in the evaluation of glomerular diseases in renal biopsies using immunofluorescence as gold standard. Study Design: Cross-sectional analytical study. Place and Duration of Study: Department of Histopathology, Armed Forces Institute of Pathology, Rawalpindi, from August 2008 to August 2009. Methodology: Seventy renal biopsy specimens fulfilling the inclusion criteria for light microscopy and immuno-fluorescence during the study period were evaluated. Antibodies to immunoglobulins (IgG, IgA, and IgM) and components of complement system (C3) were applied on 70 formalin-fixed paraffin-embedded renal biopsy specimens previously classified by means of light microscopy and immunofluorescence (IF). Staining for these antibodies was recorded as positive and negative for immunohistochemistry (IHC) and IF in paired proportions presuming IF as gold standard test. The sensitivity, specificity, positive predictive value and negative predictive value of individual antibody were calculated. Results: Of 70 patients, mean age was 33 +- 18 years ranging from 2 to 80 years. Forty five (64%) were males and 25 (36%) were females. The sensitivity, specificity and predictive values of individual antibodies to IgG, IgA, IgM and C3 were very low and generally in the range of 40 - 60%. Conclusion: The sensitivity, specificity and predictive values of immunohistochemistry on formalin-fixed paraffin-embedded renal biopsy specimens were very low and therefore, not suitable for evaluation of renal biopsies in current circumstances. (author)

  15. Influence of Acute High Glucose on Protein Abundance Changes in Murine Glomerular Mesangial Cells

    Directory of Open Access Journals (Sweden)

    Michelle T. Barati

    2016-01-01

    Full Text Available The effects of acute exposure to high glucose levels as experienced by glomerular mesangial cells in postprandial conditions and states such as in prediabetes were investigated using proteomic methods. Two-dimensional gel electrophoresis and matrix assisted laser desorption ionization time of flight mass spectrometry methods were used to identify protein expression patterns in immortalized rat mesangial cells altered by 2 h high glucose (HG growth conditions as compared to isoosmotic/normal glucose control (NG⁎ conditions. Unique protein expression changes at 2 h HG treatment were measured for 51 protein spots. These proteins could be broadly grouped into two categories: (1 proteins involved in cell survival/cell signaling and (2 proteins involved in stress response. Immunoblot experiments for a protein belonging to both categories, prohibitin (PHB, supported a trend for increased total expression as well as significant increases in an acidic PHB isoform. Additional studies confirmed the regulation of proteasomal subunit alpha-type 2 and the endoplasmic reticulum chaperone and oxidoreductase PDI (protein disulfide isomerase, suggesting altered ER protein folding capacity and proteasomal function in response to acute HG. We conclude that short term high glucose induces subtle changes in protein abundances suggesting posttranslational modifications and regulation of pathways involved in proteostasis.

  16. Correlation of Serum Cystatin C with Glomerular Filtration Rate in Patients Receiving Platinum-Based Chemotherapy.

    Science.gov (United States)

    Cavalcanti, Ernesta; Barchiesi, Vittoria; Cerasuolo, Dionigio; Di Paola, Flaviano; Cantile, Monica; Cecere, Sabrina Chiara; Pignata, Sandro; Morabito, Alessandro; Costanzo, Raffaele; Di Maio, Massimo; Perrone, Francesco

    2016-01-01

    Objectives . Serum cystatin C seems to be an accurate marker of glomerular filtration rate (GFR) compared to serum creatinine. The aim of this work was to explore the possibility of using serum cystatin C instead of serum creatinine to early predict renal failure in cancer patients who received platinum based chemotherapy. Design and Methods . Serum creatinine, serum cystatin C concentrations, and GFR were determined simultaneously in 52 cancer patients received carboplatin-based or cisplatin-based chemotherapy. Serum creatinine was assayed on Cobas C6000-Roche, serum cystatin C assay was performed on AIA 360-Tosoh, and GFR was determined in all patients, before the first cycle of chemotherapy and before the subsequent administrations. Results . In the overall series, for the prediction of a fall of GFR cystatin C was 0,667 and the best threshold was 1.135 mg/L (sensitivity 90.5%, specificity 61.1%). For a GFR fall cystatin C was 74.3% and the best threshold was 1.415 mg/L (sensitivity 66.7%, specificity 73.2%). Conclusions . Baseline cystatin C values were not able to predict renal failure during subsequent treatment. In conclusion, serum cystatin C is not a reliable early marker to efficiently predict renal failure in patients receiving chemotherapy.

  17. Cystatin C as a parameter of glomerular filtration rate in patients with ovarian cancer.

    Science.gov (United States)

    Bodnar, Lubomir; Wcislo, Gabriel Benedykt; Smoter, Marta; Gasowska-Bodnar, Agnieszka; Stec, Rafał; Synowiec, Agnieszka; Szczylik, Cezary

    2010-01-01

    To evaluate the potential role of serum cystatin C as a marker of renal function in patients with ovarian cancer. Treatment of consecutive ovarian cancer patients who were eligible for chemotherapy with paclitaxel (135 mg/m²/24 h) and cisplatin (75 mg/m²) every 3 weeks in 6 cycles. Glomerular filtration rate (GFR) markers, i.e. serum levels of creatinine and cystatin C, estimated by the Cockcroft-Gault and Modification of Diet in Renal Disease formulas, were recorded before each cycle and 3 weeks after the 6th course. The median age of 34 patients was 54 years. In the initial stage of treatment, we did not observe any correlation between cystatin C and other GFR markers. We noted a significant association between cystatin C and tumor extent on spiral CT scans (diameter: >1 cm) performed at baseline (p = 0.004), and after the 1st (p = 0.03) and 2nd cycle (p = 0.026). We observed a correlation between cystatin C and CA-125 level before chemotherapy (R = 0.4; p = 0.02) and after the 1st cycle (R = 0.43; p = 0.04). The results of our study suggest that cystatin C is not a reliable marker of the GFR in ovarian cancer patients, probably due to its nature as a cysteine protease inhibitor. Copyright © 2010 S. Karger AG, Basel.

  18. Proenkephalin, Neutrophil Gelatinase-Associated Lipocalin, and Estimated Glomerular Filtration Rates in Patients With Sepsis.

    Science.gov (United States)

    Kim, Hanah; Hur, Mina; Lee, Seungho; Marino, Rossella; Magrini, Laura; Cardelli, Patrizia; Struck, Joachim; Bergmann, Andreas; Hartmann, Oliver; Di Somma, Salvatore

    2017-09-01

    Proenkephalin (PENK) has been suggested as a novel biomarker for kidney function. We investigated the diagnostic and prognostic utility of plasma PENK in comparison with neutrophil gelatinase-associated lipocalin (NGAL) and estimated glomerular filtration rates (eGFR) in septic patients. A total of 167 septic patients were enrolled: 99 with sepsis, 37 with septic shock, and 31 with suspected sepsis. PENK and NGAL concentrations were measured and GFR was estimated by using the isotope dilution mass spectrometry traceable-Modification of Diet in Renal Disease (MDRD) Study and three Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations: CKD-EPI(Cr), CDK-EPI(CysC), and CKD-EPI(Cr-CysC). The PENK, NGAL, and eGFR results were compared according to sepsis severity, presence or absence of acute kidney injury (AKI), and clinical outcomes. The PENK, NGAL, and eGFR results were significantly associated with sepsis severity and differed significantly between patients with and without AKI only in the sepsis group (all Psepsis. © The Korean Society for Laboratory Medicine

  19. Primary glomerular nephropathy among hospitalized patients in a national database in China.

    Science.gov (United States)

    Li, Jiannan; Cui, Zhao; Long, Jianyan; Huang, Wei; Wang, Jinwei; Zhang, Hong; Wang, Haibo; Zhang, Luxia; Ronco, Pierre; Zhao, Ming-Hui

    2018-03-02

    Primary glomerular nephropathy (PGN) is a leading cause of end-stage renal disease in developing countries, however, nationwide studies investigating the spectrum of PGN are limited. To evaluate the composition of various pathological types of PGN in a comprehensive geographic coverage in China, a national inpatient database covering 43.7 million patients was used in this analysis. Diagnoses were extracted from the discharge diagnoses. The percentage of patients with PGN in hospitalized patients decreased from 0.80% in 2010 to 0.67% in 2015. Among hospitalized patients with PGN, a decreasing trend of immunoglobulin A nephropathy (from 19.0% in 2010 to 10.6% in 2015) and an increasing trend of idiopathic membranous nephropathy (from 4.5% in 2010 to 8.8% in 2015) were revealed. A positive association between the percentage of idiopathic membranous nephropathy (iMN) and the exposure of particulate matter with a diameter < 2.5 μm was observed north of the Yangtze River (P < 0.001, R2 = 0.828). South of the Yangtze River, the proportion of the Zhuang population was positively correlated to the frequency of iMN (P = 0.012, r = 0.697). In conclusion, a changing spectrum of PGN was observed between 2010 and 2015 in China and both environmental and genetic factors might play pivotal roles in the pathogenesis of iMN in the Chinese population.

  20. Acute caloric restriction improves glomerular filtration rate in patients with morbid obesity and type 2 diabetes.

    Science.gov (United States)

    Giordani, I; Malandrucco, I; Donno, S; Picconi, F; Di Giacinto, P; Di Flaviani, A; Chioma, L; Frontoni, S

    2014-04-01

    The role of caloric restriction in the improvement of renal function following bariatric surgery is still unclear; with some evidence showing that calorie restriction can reduce proteinuria. However, data on the impact of caloric restriction on renal function are still lacking. Renal function, as measured by glomerular filtration rate (GFR), was evaluated in 14 patients with type 2 diabetes mellitus, morbid obesity and stage 2 chronic kidney disease before and after a 7-day very low-calory diet (VLCD). After the VLCD, both GFR and overall glucose disposal (M value) significantly increased from 72.6 ± 3.8 mL/min/1.73 m(-2) BSA to 86.9 ± 6.1 mL/min/1.73 m(-2) BSA (P=0.026) and from 979 ± 107 μmol/min(1)/m(2) BSA to 1205 ± 94 μmol/min(1)/m(2) BSA (P=0.008), respectively. A significant correlation was observed between the increase in GFR and the rise in M value (r=0.625, P=0.017). Our observation of improved renal function following acute caloric restriction before weight loss became relevant suggesting that calory restriction per se is able to affect renal function. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  1. Renal shear wave velocity and estimated glomerular filtration rate in children with chronic kidney disease.

    Science.gov (United States)

    Bruno, Costanza; Brugnara, Milena; Micciolo, Rocco; Cecchetto, Mariangela; Zuffante, Michele; Bucci, Alessandra; Zaffanello, Marco

    2016-01-01

    A shear wave velocity (SWV) value obtained by the acoustic radiation force impulse technique depends on tissue elasticity. We investigated the relationship between SWV values and the estimated glomerular filtration rate (eGFR) in children with chronic kidney disease. A total of 29 patients were enrolled in the study. There were 18 primary and 11 secondary cases of vesicoureteral reflux. eGFR was calculated using Schwartz's formulas (2012). Partial eGFR for each kidney was assessed by multiplying the eGFR by the percentage of renal function measured by means of renal (99m)Tc-dimercaptosuccinic acid scintigraphy. All ultrasound tests were done by a single qualified technician using a convex probe (frequency 4 MHz) on an S-2000 system. The mean SWV values of the two kidneys were significantly and negatively correlated with eGFR calculated with both univariate (cystatin C [Cys C] and multivariate (creatinine, Cys C, and nitrogen) equations. Of all the formulae, the strongest correlation was obtained with eGFR (Cys C). SWV of the renal cortex correlates with the eGFR of patients affected by malformative uropathies. Nevertheless, this technique needs standardization and validation.

  2. Escaping the correction for body surface area when calculating glomerular filtration rate in children

    Energy Technology Data Exchange (ETDEWEB)

    Piepsz, Amy; Tondeur, Marianne [CHU St. Pierre, Department of Radioisotopes, Brussels (Belgium); Ham, Hamphrey [University Hospital Ghent, Department of Nuclear Medicine, Ghent (Belgium)

    2008-09-15

    {sup 51}Cr ethylene diamine tetraacetic acid ({sup 51}Cr EDTA) clearance is nowadays considered as an accurate and reproducible method for measuring glomerular filtration rate (GFR) in children. Normal values in function of age, corrected for body surface area, have been recently updated. However, much criticism has been expressed about the validity of body surface area correction. The aim of the present paper was to present the normal GFR values, not corrected for body surface area, with the associated percentile curves. For that purpose, the same patients as in the previous paper were selected, namely those with no recent urinary tract infection, having a normal left to right {sup 99m}Tc MAG3 uptake ratio and a normal kidney morphology on the early parenchymal images. A single blood sample method was used for {sup 51}Cr EDTA clearance measurement. Clearance values, not corrected for body surface area, increased progressively up to the adolescence. The percentile curves were determined and allow, for a single patient, to estimate accurately the level of non-corrected clearance and the evolution with time, whatever the age. (orig.)

  3. Aging and decreased glomerular filtration rate: An elderly population-based study.

    Science.gov (United States)

    Abdulkader, Regina C R M; Burdmann, Emmanuel A; Lebrão, Maria Lúcia; Duarte, Yeda A O; Zanetta, Dirce M T

    2017-01-01

    Although a reduced glomerular filtration rate (GFR) in old people has been attributed to physiologic aging, it may be associated with kidney disease or superimposed comorbidities. This study aims to assess the prevalence of decreased GFR in a geriatric population in a developing country and its prevalence in the absence of simultaneous diseases. This is a cross-sectional study of data from the Saúde, Bem-Estar e Envelhecimento cohort study (SABE study[Health, Well-Being and Aging]), a multiple cohorts study. A multistage cluster sample composed of 1,253 individuals representative of 1,249,388 inhabitants of São Paulo city aged ≥60 years in 2010 was analyzed. The participants answered a survey on socio-demographic factors and health, had blood pressure measured and urine and blood samples collected. GFR was estimated and defined as decreased when 0.20 g/g. The prevalence of GFR cardiovascular disease (43 versus 24%, pcardiovascular disease and hypertension were associated with GFR<60 mL/min/1.73m2. Decreased GFR was highly prevalent among the geriatric population in a megalopolis of a developing country. It was rarely present without simultaneous chronic comorbidities or kidney damage.

  4. Salt sensitivity of renin secretion, glomerular filtration rate and blood pressure in conscious Sprague-Dawley rats

    DEFF Research Database (Denmark)

    Isaksson, G L; Stubbe, J; Hansen, Per Lyngs

    2014-01-01

    We hypothesized that in normal rats in metabolic steady state, (i) the plasma renin concentration (PRC) is log-linearly related to Na(+) intake (NaI), (ii) the concurrent changes in mean arterial pressure (MABP) and glomerular filtration rate (GFR) are negligible and (iii) the function PRC = f(Na...... = f(NaI) is altered by β1 -adrenoceptor blockade (metoprolol) and surgical renal denervation (DNX)....

  5. Size- and charge selectivity of glomerular filtration in Type 1 (insulin-dependent) diabetic patients with and without albuminuria

    DEFF Research Database (Denmark)

    Deckert, T; Kofoed-Enevoldsen, A; Vidal, P

    1993-01-01

    albumin excretion rate was normal in group D1; 30-100 mg/24 h in group D2; 101-300 mg/24 h in group D3 and greater than 300 mg/24 h in groups D4 and D5. Group D5 had elevated serum creatinine (above 110 mumol/l). Glomerular filtration rate and renal plasma flow were determined by constant infusion...

  6. Comparison of single point normalized and modified Gate's method for measurement of glomerular filtration rate by nuclear medicine

    International Nuclear Information System (INIS)

    Fonseca, L.M.B. da; Fonseca, N.M.; Martins, E.; Pereira, E.

    1992-01-01

    Glomerular filtration rate was measured in 22 patients (mean age 30 years) using a noninvasive modified Gates method and the results were compared to the one point normalized technique. The values obtained were 74-11.7 and 82-11.09 ml/min., respectively. The advantages of the method are its reliability, easy adaptation to small laboratories and the avoidance of blood and urine sampling. (author)

  7. Research on the influencing factors of measuring glomerular filtration rate through 99Tcm-DTPA renal dynamic imaging

    International Nuclear Information System (INIS)

    Huang Jianmin; Tang Zidu; Pan Liping; Liu Xiaomei; Xie Peng; Gao Jianqing

    2011-01-01

    Glomerular filtration rate (GFR) is an important criterion to estimate renal function. The most common way to measure GFR clinically is 99 Tc m -DTPA Renal Dynamic Imaging. However, the result may be influenced by many factors such as plasma protein binding, delineation of kidney and background region of interest, kidney depth, age and renal function and preparation of patient, nurse's operative technique, etc. The article analyzed each factor above respectively for clinical reference. (authors)

  8. Ultrastructural study of binucleation in cells of the rat adrenal glomerular zone after a prolonged low-sodium diet.

    Science.gov (United States)

    Palacios, G; Lafarga, M; Perez, R

    1976-01-01

    Binucleate cells have been found in the glomerular zone of the adrenal cortex in rats subjected to low-sodium diets. By considering the various possibilities for their production, both the findings of nuclei in process of constriction and nuclei identical in form, confronted and smaller in size than those of neighbour cells, are in agreement with an amitotic nuclear division as the possible mechanism for the formation of these cells.

  9. Label-free quantitative proteomic analysis reveals strong involvement of complement alternative and terminal pathways in human glomerular sclerotic lesions.

    Science.gov (United States)

    Zhang, Ying; Xu, Bo; Kinoshita, Naohiko; Yoshida, Yutaka; Tasaki, Masayuki; Fujinaka, Hidehiko; Magdeldin, Sameh; Yaoita, Eishin; Yamamoto, Tadashi

    2015-06-18

    Since glomerular sclerosis frequently accompanies various glomerular diseases at the end stages, it is challenging to differentiate ubiquitous biological processes underlying this pathology from those critically involved in specific diseases. Furthermore, in-depth proteomic profile of human glomerular sclerosis remains limited. In this study, human glomeruli with intermediate (i-GS) and advanced (GS) sclerotic lesions, which were excluded from specific renal diseases and assumed to be aging-related, were laser captured from macroscopically normal cortex distant from urological carcinoma, and subjected to label-free quantitative proteomic analysis. We explicate an evident increase of membrane attack complex in i-GS and GS with an up-going tendency, which is accompanied by increasing of inhibitory regulators of alternative and terminal pathways. GO annotation and IPA pathway analysis agree to these results. Proteomic findings are validated by immunohistochemical studies which indicate that alternative and terminal pathways are positively involved in the glomerular sclerosis seen in distinct renal diseases. Furthermore, proteomic analysis also demonstrates remarkable increases of complement factor B in GS and TGF-ß1 in both GS and i-GS. Identification of complement factor B implicates that on-site activation of alternative pathway may occur in injured glomeruli and stepwise increase of TGF-ß1 suggests its contribution to the progression of glomerulosclerosis. This study provides in-depth quantitative proteomic profiles of human glomeruli with intermediate and advanced sclerotic lesions. It reveals that the over-expression of alternative and terminal pathway components is significantly involved in human glomerulosclerosis seen in distinct renal diseases. Proteomic identification of the increased TGF-ß1 provides supporting evidence for the role of podocyte apoptosis leading to human glomerulosclerosis. Copyright © 2015 Elsevier B.V. All rights reserved.

  10. RENAL GLOMERULAR NUMBER AND SIZE IN AUSTRALIAN ABORIGINES, AFRICAN AMERICANS AND WHITE POPULATIONS FROM THE SAME LOCATIONS: A PRELIMINARY REPORT

    Directory of Open Access Journals (Sweden)

    John F Bertram

    2011-05-01

    Full Text Available End stage renal disease is a major health problem for Australian Aborigines and African Americans. Abnormally enlarged glomeruli are commonly observed in biopsies from Aborigines and African Americans and may represent a compensatory hypertrophic response to reduced nephron endowment. We have commenced a study examining glomerular number and size, and their associations in Australian Aborigines and whites, and US African Americans and whites. Kidneys at autopsy are perfusion-fixed and subsampled for stereological estimation of total glomerular number (Nglom; using the physical disector/fractionator combination, and mean renal corpuscle (Vcorp and glomerular volume (Vglom. Kidneys from 58 people have been studied to date with ages ranging from newborn to 84 years. Preliminary findings are: (1 an almost 9-fold range in Nglom (from 210,332 to 1,825,380 with a mean of 762,302; (2 Nglom decreased with age in adult life (p = 0.014; (3 Vcorp varied 19-fold in the series and 5.5-fold in adults; (4 Vglom was inversely correlated with Nglom (p = 0.004; (5 total renal corpuscle volume (Nglom × Vcorp ranged by a factor of 13.2; (6 kidney weight was correlated with body surface area (BSA at all ages (p < 0.001; (7 BSA-corrected kidney weight did not vary with age, it ranged from 47 g/m2 to 175 g/m2, a 3.7 fold difference, with an average of 92 ± 25 g/m2. These preliminary results have revealed several new and important correlations. No racial differences in glomerular number or size have yet been identified, but with greater sample sizes such differences may be revealed.

  11. Reduced glomerular filtration rate and its association with clinical outcome in older patients at risk of vascular events: secondary analysis.

    LENUS (Irish Health Repository)

    Ford, Ian

    2009-01-20

    Reduced glomerular filtration rate (GFR) is associated with increased cardiovascular risk in young and middle aged individuals. Associations with cardiovascular disease and mortality in older people are less clearly established. We aimed to determine the predictive value of the GFR for mortality and morbidity using data from the 5,804 participants randomized in the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER).

  12. A SAGE based approach to human glomerular endothelium: defining the transcriptome, finding a novel molecule and highlighting endothelial diversity.

    Science.gov (United States)

    Sengoelge, Guerkan; Winnicki, Wolfgang; Kupczok, Anne; von Haeseler, Arndt; Schuster, Michael; Pfaller, Walter; Jennings, Paul; Weltermann, Ansgar; Blake, Sophia; Sunder-Plassmann, Gere

    2014-08-27

    Large scale transcript analysis of human glomerular microvascular endothelial cells (HGMEC) has never been accomplished. We designed this study to define the transcriptome of HGMEC and facilitate a better characterization of these endothelial cells with unique features. Serial analysis of gene expression (SAGE) was used for its unbiased approach to quantitative acquisition of transcripts. We generated a HGMEC SAGE library consisting of 68,987 transcript tags. Then taking advantage of large public databases and advanced bioinformatics we compared the HGMEC SAGE library with a SAGE library of non-cultured ex vivo human glomeruli (44,334 tags) which contained endothelial cells. The 823 tags common to both which would have the potential to be expressed in vivo were subsequently checked against 822,008 tags from 16 non-glomerular endothelial SAGE libraries. This resulted in 268 transcript tags differentially overexpressed in HGMEC compared to non-glomerular endothelia. These tags were filtered using a set of criteria: never before shown in kidney or any type of endothelial cell, absent in all nephron regions except the glomerulus, more highly expressed than statistically expected in HGMEC. Neurogranin, a direct target of thyroid hormone action which had been thought to be brain specific and never shown in endothelial cells before, fulfilled these criteria. Its expression in glomerular endothelium in vitro and in vivo was then verified by real-time-PCR, sequencing and immunohistochemistry. Our results represent an extensive molecular characterization of HGMEC beyond a mere database, underline the endothelial heterogeneity, and propose neurogranin as a potential link in the kidney-thyroid axis.

  13. Insulin's acute effects on glomerular filtration rate correlate with insulin sensitivity whereas insulin's acute effects on proximal tubular sodium reabsorption correlate with salt sensitivity in normal subjects

    NARCIS (Netherlands)

    ter Maaten, JC; Bakker, SJL; Serne, EH; ter Wee, PM; Gans, ROB

    1999-01-01

    Background. Insulin induces increasing distal tubular sodium reabsorption. Opposite effects of insulin to offset insulin-induced sodium retention are supposedly increases in glomerular filtration rate (GFR) and decreases in proximal tubular sodium reabsorption. Defects in these opposing effects

  14. Expression of Toll-Like Receptor 2 in Glomerular Endothelial Cells and Promotion of Diabetic Nephropathy by Porphyromonas gingivalis Lipopolysaccharide

    Science.gov (United States)

    Hatakeyama, Yuji; Ishikawa, Hiroyuki; Tsuruga, Eichi

    2014-01-01

    The toll-like receptor (TLR) has been suggested as a candidate cause for diabetic nephropathy. Recently, we have reported the TLR4 expression in diabetic mouse glomerular endothelium. The study here investigates the effects of the periodontal pathogen Porphyromonas gingivalis lipopolysaccharide (LPS) which is a ligand for TLR2 and TLR4 in diabetic nephropathy. In laser-scanning microscopy of glomeruli of streptozotocin- and a high fat diet feed-induced type I and type II diabetic mice, TLR2 localized on the glomerular endothelium and proximal tubule epithelium. The TLR2 mRNA was detected in diabetic mouse glomeruli by in situ hybridization and in real-time PCR of the renal cortex, the TLR2 mRNA amounts were larger in diabetic mice than in non-diabetic mice. All diabetic mice subjected to repeated LPS administrations died within the survival period of all of the diabetic mice not administered LPS and of all of the non-diabetic LPS-administered mice. The LPS administration promoted the production of urinary protein, the accumulation of type I collagen in the glomeruli, and the increases in IL-6, TNF-α, and TGF-β in the renal cortex of the glomeruli of the diabetic mice. It is thought that blood TLR ligands like Porphyromonas gingivalis LPS induce the glomerular endothelium to produce cytokines which aid glomerulosclerosis. Periodontitis may promote diabetic nephropathy. PMID:24835775

  15. Olfactory bulb glomerular NMDA receptors mediate olfactory nerve potentiation and odor preference learning in the neonate rat.

    Directory of Open Access Journals (Sweden)

    Rebecca Lethbridge

    Full Text Available Rat pup odor preference learning follows pairing of bulbar beta-adrenoceptor activation with olfactory input. We hypothesize that NMDA receptor (NMDAR-mediated olfactory input to mitral cells is enhanced during training, such that increased calcium facilitates and shapes the critical cAMP pattern. Here, we demonstrate, in vitro, that olfactory nerve stimulation, at sniffing frequencies, paired with beta-adrenoceptor activation, potentiates olfactory nerve-evoked mitral cell firing. This potentiation is blocked by a NMDAR antagonist and by increased inhibition. Glomerular disinhibition also induces NMDAR-sensitive potentiation. In vivo, in parallel, behavioral learning is prevented by glomerular infusion of an NMDAR antagonist or a GABA(A receptor agonist. A glomerular GABA(A receptor antagonist paired with odor can induce NMDAR-dependent learning. The NMDA GluN1 subunit is phosphorylated in odor-specific glomeruli within 5 min of training suggesting early activation, and enhanced calcium entry, during acquisition. The GluN1 subunit is down-regulated 3 h after learning; and at 24 h post-training the GluN2B subunit is down-regulated. These events may assist memory stability. Ex vivo experiments using bulbs from trained rat pups reveal an increase in the AMPA/NMDA EPSC ratio post-training, consistent with an increase in AMPA receptor insertion and/or the decrease in NMDAR subunits. These results support a model of a cAMP/NMDA interaction in generating rat pup odor preference learning.

  16. Amikacin maturation model as a marker of renal maturation to predict glomerular filtration rate and vancomycin clearance in neonates.

    Science.gov (United States)

    Zhao, Wei; Biran, Valérie; Jacqz-Aigrain, Evelyne

    2013-12-01

    Amikacin clearance has recently been proposed as a marker of renal maturation in neonates. However, the predictive value of this marker is still unknown. The objective of the present exploratory study was to evaluate the predictive performance of renal maturation model derived from amikacin to predict the glomerular filtration rate (GFR) and vancomycin clearance in neonates. The GFR and vancomycin clearance in neonates were predicted using a maturation model derived from amikacin via estimation and simulation in a cohort of 116 neonates using non-linear mixed-effects modeling NONMEM® software. Our results demonstrate good correlations between predicted and observed GFR and vancomycin clearance in neonates. The square of the correlation coefficient, and means of the prediction error (2.5th-97.5th percentiles) and absolute prediction error (2.5th-97.5th percentiles) are 0.96, 1.2 % (-39.7 to 30.0 %) and 12.3 % (0.4-39.7 %), respectively, for GFR, and 0.97, -11.3 % (-38.2 to 15.4 %) and 14.0 % (0.5-38.2 %), respectively, for vancomycin. The prediction error is not significantly correlated with age. An amikacin maturation model can precisely reflect maturation of glomerular filtration and thus predict the dosage regimens of other renally excreted drugs by glomerular filtration in neonates.

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

    DEFF Research Database (Denmark)

    Strandgaard, S; Kamper, A; Skaarup, P

    1988-01-01

    1. Glomerular and tubular function was studied before and 2 months after unilateral nephrectomy in 14 healthy kidney donors by measurement of the clearances of 51Cr-labelled ethylenediaminetetra-acetate, lithium, beta 2-microglobulin, albumin and immunoglobulin G. 2. The glomerular filtration rate...... APR and a fall in FPR. The proximal tubules thus initially handle the increased filtrate load by passing it on to more distal nephron segments.(ABSTRACT TRUNCATED AT 250 WORDS)...

  18. The value of IgG-uria in predicting renal failure in idiopathic glomerular diseases. A long-term follow-up study.

    OpenAIRE

    Tofik, Rafid; Aziz, Rawa; Reda, Ahmed; Rippe, Bengt; Bakoush, Omran

    2011-01-01

    Abstract Background. Proteinuria is the hallmark of glomerular disease and non-selective proteinuria is often associated with progression to renal failure. The predictive value of urine IgG excretion was studied comprehensively in patients with nephrotic syndrome. In the present follow-up study, we examine the predictive value of IgG-uria in patients with idiopathic glomerular diseases with a wide range of proteinuia. Methods. A total of 189 (113 males and 76 females) patients with idiopathic...

  19. Barrier mechanisms in the Drosophila blood-brain barrier

    Directory of Open Access Journals (Sweden)

    Samantha Jane Hindle

    2014-12-01

    Full Text Available The invertebrate blood-brain barrier field is growing at a rapid pace and, in recent years, studies have shown a physiologic and molecular complexity that has begun to rival its vertebrate counterpart. Novel mechanisms of paracellular barrier maintenance through GPCR signaling were the first demonstrations of the complex adaptive mechanisms of barrier physiology. Building upon this work, the integrity of the invertebrate blood-brain barrier has recently been shown to require coordinated function of all layers of the compound barrier structure, analogous to signaling between the layers of the vertebrate neurovascular unit. These findings strengthen the notion that many blood-brain barrier mechanisms are conserved between vertebrates and invertebrates, and suggest that novel findings in invertebrate model organisms will have a significant impact on the understanding of vertebrate BBB functions. In this vein, important roles in coordinating localized and systemic signaling to dictate organism development and growth are beginning to show how the blood-brain barrier can govern whole animal physiologies. This includes novel functions of blood-brain barrier gap junctions in orchestrating synchronized neuroblast proliferation, and of blood-brain barrier secreted antagonists of insulin receptor signaling. These advancements and others are pushing the field forward in exciting new directions. In this review, we provide a synopsis of invertebrate blood-brain barrier anatomy and physiology, with a focus on insights from the past 5 years, and highlight important areas for future study.

  20. Linguistic Barriers and Bridges

    DEFF Research Database (Denmark)

    Thuesen, Frederik

    2016-01-01

    The influence of language on social capital in low-skill and ethnically diverse workplaces has thus far received very limited attention within the sociology of work. As the ethnically diverse workplace is an important social space for the construction of social relations bridging different social...... and intercultural communication, this article analyses interviews with 31 employees from two highly ethnically diverse Danish workplaces. The article shows how linguistic barriers such as different levels of majority language competence and their consequent misunderstandings breed mistrust and hostility, whilst...... communication related to collaboration and ‘small talk’ may provide linguistic bridges to social capital formation....

  1. [Barrier methods of contraception].

    Science.gov (United States)

    Goldsmith, A; Edelman, D A

    1982-01-01

    Vaginal methods of contraception were the earliest types used and some references to them date back to antiquity. Most of the vaginal contraceptive agents identified by the ancient Greeks, Indians, Japanese, and Chinese have been found in modern laboratory tests to have spermicidal properties, but it is doubtful that the methods were fully reliable or were used by many people. During the 19th century the condom, vaginal spermicides, and diaphragm became available. The development of nonoxynol-9 and other nonirritating but effective spermicidal agents improved vaginal contraceptives greatly by the 1950s, but starting in the 1960s newer methods began to replace the vaginal methods. Interest in barrier methods has been reawakened somewhat by concern about the health effects of hormonal methods. At present all barrier methods leave something to be desired. Failure rates of 3-30% for barrier methods in general have been estimated, but the higher rates are believed due to incorrect or inconsistent use. Theoretical failure rates of condoms and diaphragms have been estimated at 3/100 women-years, but in actual use failure rates may reach 15 for condoms and 13 for diaphragms used with spermicides. Use-effectiveness rates are greatly influenced by motivation. For a variety of reasons, the acceptability of barrier methods is low, especially in developing countries. New developments in spermicidal agents include sperm inhibitors, which impede the fertilizing capacity of sperm rather than attempting a spermicidal effect; a number of such agents have been studied and have proven more effective in animal tests than conventional spermicides. Neosampoon, a new spermicidal foam, has attracted an increasing number of users, especially in developing countries. A new condom, made of thin polymers and containing a standard dose of nonoxynol-9, has been designed to dissolve in the vaginal fluid. Further studies are needed of its acceptability, efficacy, and side effects before it becomes

  2. Support or Barrier?

    DEFF Research Database (Denmark)

    Sanden, Guro Refsum; Lønsmann, Dorte

    employees use to cross language boundaries in their everyday work, and, secondly, how these practices relate to top-down language management in the case companies. Our findings show that employees are often dependent on ad hoc and informal solutions in cross- language situations, which leads us......This study offers a critical look at how corporate-level language management influences front-line language practices among employees in three multinational corporations (MNCs) headquartered in Scandinavia. Based on interview and document data, we examine, firstly, what front-line practices...... to a discussion of how a company’s language policy may be seen as both support and a barrier....

  3. Association of estimated glomerular filtration rate with muscle function in older persons who have fallen.

    Science.gov (United States)

    Tap, Lisanne; Boyé, Nicole D A; Hartholt, Klaas A; van der Cammen, Tischa J M; Mattace-Raso, Francesco U S

    2018-03-01

    studies suggest that estimated glomerular filtration rate (eGFR) is less reliable in older persons and that a low serum-creatinine might reflect reduced muscle mass rather than high kidney function. This study investigates the possible relationship between eGFR and multiple elements of physical performance in older fallers. baseline data of the IMPROveFALL-study were examined in participants ≥65 years. Serum-creatinine based eGFR was classified as normal (≥90 ml/min), mildly reduced (60-89 ml/min) or moderately-severely reduced (<60 ml/min). Timed-Up-and-Go-test and Five-Times-Sit-to-Stand-test were used to assess mobility; calf circumference and handgrip strength to assess muscle status. Ancova models adjusted for age, sex, Charlson comorbidity index and body mass index were performed. a total of 578 participants were included. Participants with a normal eGFR had lower handgrip strength than those with a mildly reduced eGFR (-9.5%, P < 0.001) and those with a moderately-severely reduced eGFR (-6.3%, P = 0.033) with mean strengths of 23.4, 25.8 and 24.9 kg, respectively. Participants with a normal eGFR had a smaller calf circumference than those with a mildly reduced eGFR (35.5 versus 36.5 cm, P = 0.006). Mean time to complete the mobility tests did not differ. in this study we found that older fallers with an eGFR ≥ 90 ml/min had smaller calf circumference and up to 10% lower handgrip strength than those with a reduced eGFR. This lower muscle mass is likely to lead to an overestimation of kidney function. This outcome therefore supports the search for biomarkers independent of muscle mass to estimate kidney function in older persons.

  4. Use of glomerular filtration rate estimating equations for drug dosing in HIV-positive patients

    Science.gov (United States)

    Okparavero, Aghogho A; Tighiouart, Hocine; Krishnasami, Zipporah; Wyatt, Christina M; Graham, Hiba; Hellinger, James; Inker, Lesley A

    2014-01-01

    Background Current HIV treatment guidelines recommend using the Cockcroft-Gault equation for drug dosing adjustments. The use of newer glomerular filtration rate (GFR) estimating equations for drug dosing and the appropriateness of physician antiretroviral dosing based on estimated kidney function have not been studied in an HIV-positive population. Methods We evaluated concordance between measured and estimated GFR for the assignment of kidney function categories designated by the Food and Drug Administration (FDA) Guidance for Industry for pharmacokinetic studies, and appropriateness of physician antiretroviral drug dosing for level of kidney function in 200 HIV-positive patients on stable antiretroviral therapy. Estimated kidney function was determined using the Chronic Kidney Disease-Epidemiology collaboration (CKD-EPI), Modification of Diet in Renal Disease (MDRD) Study and Cockcroft-Gault equations. Results For assignment of FDA-designated kidney function categories, concordance rates between measured and estimated GFR using the CKD-EPI, MDRD Study and Cockcroft-Gault equations were 79%, 71% and 77%, respectively. This pattern was consistent across most subgroups. When actual prescribed dosages were compared to recommended dosages based on the level of estimated kidney function, 3% to 19% of study participants were prescribed higher than recommended dosages. The largest discordance between prescribed and recommended dosages was observed for the Cockcroft-Gault equation. Conclusions The CKD-EPI equation has the highest concordance with measured GFR for the assignment of FDA-designated kidney function categories. Its use may lead to lower dosing related errors in HIV-infected US adults on stable antiretroviral therapy. More education is required with respect to dose adjustment for level of kidney function. PMID:23963249

  5. Cardiac resynchronization therapy improves renal function in human heart failure with reduced glomerular filtration rate.

    Science.gov (United States)

    Boerrigter, Guido; Costello-Boerrigter, Lisa C; Abraham, William T; Sutton, Martin G St John; Heublein, Denise M; Kruger, Kristin M; Hill, Michael R S; McCullough, Peter A; Burnett, John C

    2008-09-01

    Renal dysfunction is an important independent prognostic factor in heart failure (HF). Cardiac resynchronization therapy (CRT) improves functional status and left ventricular (LV) function in HF patients with ventricular dyssynchrony, but the impact of CRT on renal function is less defined. We hypothesized that CRT would improve glomerular filtration rate as estimated by the abbreviated Modification of Diet in Renal Disease equation (eGFR). The Multicenter InSync Randomized Clinical Evaluation (MIRACLE) study evaluated CRT in HF patients with NYHA Class III-IV, ejection fraction or=130 ms. Patients were evaluated before and 6 months after randomization to control (n = 225) or CRT (n = 228). Patients were categorized according to their baseline eGFR: >or=90 (category A), 60

  6. Reduction in non-glomerular renal clearance of the caffeine metabolite 1-methylxanthine by probenecid.

    Science.gov (United States)

    Rengelshausen, J; Göggelmann, C; Burhenne, J; Riedel, K D; Mikus, G; Walter-Sack, I; Haefeli, W E

    2007-08-01

    Urinary caffeine metabolic ratios used to quantify the activity of numerous drug-metabolizing enzymes are an established component of cocktail approaches for metabolic phenotyping. Because in vitro evidence suggests that 1-methylxanthine (1-MX), a major caffeine metabolite, is actively secreted into urine by organic anion transporters (hOATs), coadministration of renal hOAT inhibitors like probenecid may impair these procedures. In a randomized, placebo-controlled, double-blind crossover design, single oral doses of 300 mg caffeine with oral coadministration of placebo or 500 mg probenecid 3 times daily for 2 days were administered to 7 healthy men. The plasma and urine concentrations of caffeine and its major metabolites 1,7-dimethylxanthine (1,7-DMX) and 1-MX were determined by high-performance liquid chromatography. Coadministration of probenecid resulted in a 34% reduction of the renal clearance of 1-MX (mean +/- SD 190 +/- 42 versus 290 +/- 83 ml min(-1), 95% CI on difference 0.2, 200, p = 0.04) with a 41% reduction in its estimated non-glomerular clearance. The renal clearances of caffeine and 1,7-DMX and the area under the plasma concentration-time curves of all substances were not significantly changed. 1-MX undergoes renal tubular secretion which is substantially reduced by probenecid, possibly due to inhibition of renal hOATs. This inhibition may explain the influence of probenecid on urinary caffeine metabolic ratios and, thus, its impact on the assessment of enzyme activities. It also suggests that 1-MX might serve as a model substrate for the renal tubular transport of organic anions.

  7. Transcutaneous glomerular filtration rate measurement in a canine animal model of chronic kidney disease.

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    Mondritzki, Thomas; Steinbach, Sarah M L; Boehme, Philip; Hoffmann, Jessica; Kullmann, Maximilian; Schock-Kusch, Daniel; Vogel, Julia; Kolkhof, Peter; Sandner, Peter; Bischoff, Erwin; Hüser, Jörg; Dinh, Wilfried; Truebel, Hubert

    Quantitative assessment of renal function by measurement of glomerular filtration rate (GFR) is an important part of safety and efficacy evaluation in preclinical drug development. Existing methods are often time consuming, imprecise and associated with animal burden. Here we describe the comparison between GFR determinations with sinistrin (PS-GFR) and fluorescence-labelled sinistrin-application and its transcutaneous detection (TD-GFR) in a large animal model of chronic kidney disease (CKD). TD-GFR measurements compared to a standard method using i.v. sinistrin were performed in a canine model. Animals were treated with one-sided renal wrapping (RW) followed by renal artery occlusion (RO). Biomarker and remote hemodynamic measurements were performed. Plasma sinistrin in comparison to transcutaneous derived GFR data were determined during healthy conditions, after RW and RW+RO. RW alone did not led to any significant changes in renal function, neither with PS-GFR nor TD-GFR. Additional RO showed a rise in blood pressure (+68.0mmHg), plasma urea (+28.8mmol/l), creatinine (+224,4μmol/l) and symmetric dimethylarginine (SDMA™; +12.6μg/dl). Plasma sinistrin derived data confirmed the expected drop (-44.7%, p<0.0001) in GFR. The calculated transcutaneous determined Fluorescein Isothiocyanate (FITC)-sinistrin GFR showed no differences to plasma sinistrin GFR at all times. Both methods were equaly sensitive to diagnose renal dysfunction in the affected animals. Renal function assessment using TD-GFR is a valid method to improve preclinical drug discovery and development. Furthermore, TD-GFR method offers advantages in terms of reduced need for blood sampling and thus decreasing animal burden compared to standard procedures. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Phaleria macrocarpa reduces glomerular growth factor expression in alloxan-induced diabetic rats

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    Evy Sulistyoningrum

    2013-08-01

    Full Text Available Background Diabetic nephropathy (DN is the most serious complication of diabetes, causing end-stage renal disease throughout the world. Recent studies have reported a direct role of vascular endothelial growth factor (VEGF and transforming growth factor-â (TGF-â in DN pathogenesis. VEGF and TGF-â are expressed early in glomeruli in response to hyperglycemia. Active substances of Phaleria macrocarpa (PM pericarp are known to have nephroprotective effects. This study aimed to evaluate the effects of Phaleria macrocarpa (Scheff. Boerl pericarp extract on VEGF and TGF-â expression in alloxan-induced diabetic rats. Methods An experimental study was conducted on twenty five male albino (Sprague Dawley rats divided into five groups (of five each: normal control; diabetic; diabetic + metformin 100 mg/kgBW; diabetic + methanolic PM extract 250 mg/kgBW; and diabetic + aqueous PM extract 250 mg/kgBW. Diabetes was induced by alloxan monohydrate 150 mg/BW intraperitoneally. Treatment was given for 3 weeks. VEGF and TGF-â expression analysis was performed by means of immunohistochemical technique. Differences between groups were assessed by one-way ANOVA. Results VEGF expression in the PM extract group was significantly lower than that in the diabetic group and even metformin group (p<0.01. TGF-â expression in methanolic PM extract group was significantly lower than in diabetic and metformin group (p<0.01, but aqueous PM extract group only showed significancy when compared with diabetic group (p< 0.01. Conclusions Phaleria macrocarpa pericarp extract reduces glomerular expression of TGF-â and VEGF in alloxan-induced diabetic rats.

  9. The Mayo Clinic quadratic equation improves the prediction of glomerular filtration rate in diabetic subjects.

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    Rigalleau, Vincent; Lasseur, Catherine; Raffaitin, Christelle; Perlemoine, Caroline; Barthe, Nicole; Chauveau, Philippe; Combe, Christian; Gin, Henri

    2007-03-01

    Although recommended, both the Cockcroft and Gault formula (CG) and the modification of diet in renal disease (MDRD) equation are not ideally predictive of glomerular filtration rate (GFR) in diabetic subjects; we tested whether the new Mayo Clinic Quadratic (MCQ) equation performed better. In 200 diabetic subjects with a wide range of renal function, GFR was measured by 51Cr-EDTA clearance, and compared with the results of the three predictive equations by regression analysis and Bland and Altman procedures. The correlations with body mass index, age and albumin excretion rates were tested. The precisions (absolute difference as percentage), diagnostic accuracies [receiver operating characteristic (ROC) curves for the diagnosis of moderate and severe chronic kidney disease (CKD)], and the results of stratification according to the KDOQ classification were compared. The CG and MCQ overestimated mean GFR, whereas the MDRD underestimated it. Correlation coefficients and areas under the ROC curves were better for the MDRD and the MCQ as compared with the CG, which was biased by body weight (+30% overestimation in obese diabetic subjects). The absolute differences with true GFR were slightly lower for the MDRD than the MCQ, and both better than the CG. Both the MDRD and MCQ correctly stratified 65% of the subjects (CG: 55%, P<0.05). In contrast with the MDRD, the MCQ did not underestimate normal GFR, and its performance for stratification was uniformly good over a wide GFR range. In diabetic subjects, the MCQ has a similar diagnostic performance to the MDRD, but it does not underestimate normal GFR, which is an important advantage.

  10. Glomerulonefritis fibrilar: Una rara forma de enfermedad glomerular por depósitos organizados

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    Marta B. Cabrera

    2011-10-01

    Full Text Available Se describe el caso de una mujer de 67 años de edad que consultó por debilidad y astenia, constatándose proteinuria de rango nefrótico y dislipemia. Se realizó punción para biopsia renal, la que se analizó por microscopia óptica, inmunofluorescencia y microscopia electrónica de transmisión. El análisis ultra-estructural reveló la existencia de depósitos fibrilares organizados, rectos, no ramificados, cuyo espesor osciló entre 15 y 20 nm. Dichas fibrillas ópticamente se veían como una expansión mesangial discretamente nodular, ligeramente PAS positiva, rojo Congo negativa y débilmente positiva para IgG. El diagnóstico fue glomerulonefritis fibrilar. Las enfermedades glomerulares por depósitos organizados pueden exhibir superposición sindrómica e histopatológica. Por tal motivo, resulta de importancia una primera separación entre aquellas rojo Congo positivas o negativas, siendo en este último caso la microscopia electrónica de transmisión la que diferencia dos entidades: la glomerulonefritis fibrilar y la glomerulonefritis inmunotactoide. Esta diferencia se apoya no sólo en las características ultraestructurales, sino en sus características clínicas. La glomerulonefritis inmunotactoide muestra una fuerte asociación con procesos linfoproliferativos, a diferencia de lo que ocurre con la glomerulonefritis fibrilar.

  11. Single- versus multiple-sample method to measure glomerular filtration rate.

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    Delanaye, Pierre; Flamant, Martin; Dubourg, Laurence; Vidal-Petiot, Emmanuelle; Lemoine, Sandrine; Cavalier, Etienne; Schaeffner, Elke; Ebert, Natalie; Pottel, Hans

    2018-01-08

    There are many different ways to measure glomerular filtration rate (GFR) using various exogenous filtration markers, each having their own strengths and limitations. However, not only the marker, but also the methodology may vary in many ways, including the use of urinary or plasma clearance, and, in the case of plasma clearance, the number of time points used to calculate the area under the concentration-time curve, ranging from only one (Jacobsson method) to eight (or more) blood samples. We collected the results obtained from 5106 plasma clearances (iohexol or 51Cr-ethylenediaminetetraacetic acid (EDTA)) using three to four time points, allowing GFR calculation using the slope-intercept method and the Bröchner-Mortensen correction. For each time point, the Jacobsson formula was applied to obtain the single-sample GFR. We used Bland-Altman plots to determine the accuracy of the Jacobsson method at each time point. The single-sample method showed within 10% concordances with the multiple-sample method of 66.4%, 83.6%, 91.4% and 96.0% at the time points 120, 180, 240 and ≥300 min, respectively. Concordance was poorer at lower GFR levels, and this trend is in parallel with increasing age. Results were similar in males and females. Some discordance was found in the obese subjects. Single-sample GFR is highly concordant with a multiple-sample strategy, except in the low GFR range (<30 mL/min). © The Author 2018. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

  12. Water-soluble vitamins in people with low glomerular filtration rate or on dialysis: a review.

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    Clase, Catherine M; Ki, Vincent; Holden, Rachel M

    2013-01-01

    People with low glomerular filtration rate and people on dialysis are spontaneously at risk for vitamin deficiency because of the potential for problems with decreased appetite and decreased sense of smell and taste, leading to decreased intake, and because decreased energy or decreased cognitive ability results in difficulties in shopping and cooking. Imposed dietary restrictions because of their renal dysfunction and because of comorbidities such as hypertension and diabetes exacerbate this problem. Finally, particularly for water-soluble vitamins, loss may occur into the dialysate. We did not identify any randomized trials of administering daily doses close to the recommended daily allowances of these vitamins. In people who are eating at all, deficiencies of B5 and B7 seem unlikely. It is unclear whether supplements of B2 and B3 are necessary. Because of dialyzability and documented evidence of insufficiency in dialysis patients, B1 supplementation is likely to be helpful. B6, B9, and B12 are implicated in the hyperhomocysteinemia observed in patients on dialysis. These vitamins have been studied in combinations, in high doses, with the hope of reducing cardiovascular outcomes. No reductions in patient-important outcomes were seen in adequately powered randomized trials. Because of their involvement in the homocysteine pathway, however, supplementation with lower doses, close to the recommended daily allowances, may be helpful. Vitamin C deficiency is common in patients on dialysis who are not taking supplements: low-dose supplements are warranted. Vitamins for dialysis patients contain most or all of the B vitamins and low-dose vitamin C. We are not aware of any medical reasons to choose one over another. © 2013. The Authors. Seminars in Dialysis published by Wiley Periodicals, Inc.

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

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    Edoardo Vitolo

    2016-10-01

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

  14. Pattern of glomerular disease in Nepal: A single-center experience

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    S Khakurel

    2015-01-01

    Full Text Available Glomerulonephritis (GN is the most common cause of end-stage renal disease in Nepal. The aim of the present study is to determine the clinical presentation and histological pattern of GN with and without immunofluorescence (IF. It is a retrospective analysis of all GN patients with kidney biopsy at the Bir Hospital from January 2000 to April 2009. The clinical presentation, blood pressure, urine analysis, 24-h urinary protein, biochemistry, hemoglobin, antinuclear antibody, anti-ds DNA, light microscopy (LM and IF findings of kidney biopsies were computed from hospital records. SPSS package was used for analysis. A total of 398 patients [LM 204 (51% and LM plus IF 194 (49%] were analyzed. The mean age of the study patients was 28 ± 13.6 years (range 7-74; males comprised 52.8% and females 47.2% of the patients; 51% were between 16 and 30 years of age. The common clinical presentations included nephrotic syndrome (NS, seen in 69% of the patients, followed by acute nephritic syndrome, seen in 14.4% of the patients. Kidney biopsy without IF showed mesangial proliferative GN (MesPGN in 21.1%, membranoproliferative GN (MPGN in 18.6%, membranous nephropathy (MN in 14.2%, minimal change disease (MCD in 12.3% and focal and segmental glomerulosclerosis (FSGS in 9.8% of the cases. With IF, MCD was seen in 23.2%, FSGS in 18%, MN in 11.9%, IgA nephropathy in 9.8%, MesPGN in 8.2%, MPGN in 4.1% and crescentic GN in 3.1% of the cases. Lupus nephritis in the cases GN was most common in young adults, with the majority presenting with NS. MCD and FSGS were the most common glomerular lesions; over-diagnosis of MesPGN and MPGN by LM could be due to exclusion of IgA nephropathy.

  15. Anti-glomerular basement membrane disease: Case series from a tertiary center in North India

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    D Prabhakar

    2017-01-01

    Full Text Available Anti-glomerular basement (anti-GBM disease is an uncommon disorder with a bimodal age of presentation. Patients presenting with dialysis-dependent renal failure have poor renal outcomes. There is limited data regarding the clinical presentation and outcomes of anti-GBM disease from India. We conducted this prospective study to analyze the clinical presentation and outcomes of anti-GBM disease at a large tertiary care hospital in North India over 1½ years. Subjects with a biopsy proven anti-GBM disease (light microscopic examination showing crescents and immunofluorescence examination showing linear deposition of IgG with or without positive anti-GBM antibodies in serum were included in the study and followed-up for at least 12 months. All the patients were treated with steroids, cyclophosphamide, and plasma exchange. A total of 17 patients (nine males were included. The mean age at presentation was 39.11 ± 16.58 (range 11–72 years. Twelve patients (70% presented with rapidly progressive glomerulonephritis (RPGN, 4 (23.5% presented with Goodpasture syndrome, while 1 (5.8% had nephritic syndrome, 7 (41% were hypertensive, and 14 (82.3% required dialysis at the time of presentation. Four patients (23.5% had associated anti-neutrophil cytoplasmic antibody positivity (anti-myeloperoxidase antibodies in all. Fourteen (87.5% patients had crescentic glomerulonephritis, while 5 (31.25% showed necrotizing (n = 4 or granulomatous (n = 1 in the vasculitis. Of 16 patients who received treatment, four (23.25% achieved complete remission. In this single-center study, the majority of anti-GBM disease patients presented with RPGN and had crescentic glomerulonephritis on biopsy with poor treatment outcome.

  16. Validation of predictive equations for glomerular filtration rate in the Saudi population

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    Al Wakeel Jamal

    2009-01-01

    Full Text Available Predictive equations provide a rapid method of assessing glomerular filtration rate (GFR. To compare the various predictive equations for the measurement of this parameter in the Saudi population, we measured GFR by the Modification of Diet in Renal Disease (MDRD and Cockcroft-Gault formulas, cystatin C, reciprocal of cystatin C, creatinine clearance, reciprocal of creatinine, and inulin clearance in 32 Saudi subjects with different stages of renal disease. We com-pared GFR measured by inulin clearance and the estimated GFR by the equations. The study included 19 males (59.4% and 13 (40.6% females with a mean age of 42.3 ± 15.2 years and weight of 68.6 ± 17.7 kg. The mean serum creatinine was 199 ± 161 μmol/L. The GFR measured by inulin clearance was 50.9 ± 33.5 mL/min, and the estimated by Cockcroft-Gault and by MDRD equations was 56.3 ± 33.3 and 52.8 ± 32.0 mL/min, respectively. The GFR estimated by MDRD revealed the strongest correlation with the measured inulin clearance (r= 0.976, P= 0.0000 followed by the GFR estimated by Cockcroft-Gault, serum cystatin C, and serum creatinine (r= 0.953, P= 0.0000 (r= 0.787, P= 0.0001 (r= -0.678, P= 0.001, respectively. The reciprocal of cystatin C and serum creatinine revealed a correlation coefficient of 0.826 and 0.93, respectively. Cockroft-Gault for-mula overestimated the GFR by 5.40 ± 10.3 mL/min in comparison to the MDRD formula, which exhibited the best correlation with inulin clearance in different genders, age groups, body mass index, renal transplant recipients, chronic kidney disease stages when compared to other GFR predictive equations.

  17. Clinical predictors of the estimated glomerular filtration rate 1 year after radical nephrectomy in Japanese patients

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    Shuichi Shimada

    2017-07-01

    Full Text Available Purpose: To evaluate renal function 1 year after radical nephrectomy (RN for renal cell carcinoma, the preoperative predictors of postnephrectomy renal function were investigated by sex, and equations to predict the estimated glomerular filtration rate (eGFR 1 year after RN were developed. Materials and Methods: A total of 525 patients who underwent RN between May 2007 and August 2011 at Tohoku University Hospital and its affiliated hospitals were prospectively evaluated. Overall, 422 patients were analyzed in this study. Results: Independent preoperative factors associated with postnephrectomy renal function were different in males and females. Preoperative eGFR, age, tumor size, and body mass index (BMI were independent factors in males, while tumor size and BMI were not independent factors in females. The equations developed to predict eGFR 1 year after RN were: Predicted eGFR in males (mL/min/1.73 m2 =27.99-(0.196×age+(0.497×eGFR+(0.744×tumor size-(0.339×BMI; and predicted eGFR in females=44.57- (0.275×age+(0.298×eGFR. The equations were validated in the validation dataset (R2 =0.63, p<0.0001 and R2 =0.31, p<0.0001, respectively. Conclusions: The developed equations by sex enable better prediction of eGFR 1 year after RN. The equations will be useful for preoperative patient counseling and selection of the type of surgical procedure in elective partial or RN cases.

  18. Derivation of new equations to estimate glomerular filtration rate in pediatric oncology patients.

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    Millisor, Vanessa E; Roberts, Jessica K; Sun, Yilun; Tang, Li; Daryani, Vinay M; Gregornik, David; Cross, Shane J; Ward, Deborah; Pauley, Jennifer L; Molinelli, Alejandro; Brennan, Rachel C; Stewart, Clinton F

    2017-06-02

    Monitoring renal function is critical in treating pediatric patients, especially when dosing nephrotoxic agents. We evaluated the validity of the bedside Schwartz and Brandt equations in pediatric oncology patients and developed new equations for estimated glomerular filtration rate (eGFR) in these patients. A retrospective analysis was conducted comparing eGFR using the bedside Schwartz and Brandt equations to measured GFR (mGFR) from technetium-99m diethylenetriamine pentaacetic acid ( 99m Tc-DTPA) between January 2007 and August 2013. An improved equation to estimate GFR was developed, simplified, and externally validated in a cohort of patients studied from September 2013 to June 2015. Carboplatin doses calculated from 99m Tc-DTPA were compared with doses calculated by GFR-estimating equations. Overall, the bedside Schwartz and Brandt equations did not precisely or accurately predict measured GFR (mGFR). Using a data subset, we developed a five-covariate equation, which included height, serum creatinine, age, blood urea nitrogen (BUN), and gender, and a simplified version (two-covariates), which contained height and serum creatinine. These equations were used to estimate GFR in 2036 studies, resulting in precise and accurate predictors of mGFR values. Equations were validated in an external cohort of 570 studies; both new equations were more accurate in calculating carboplatin doses than either the bedside Schwartz or Brandt equation. Two new equations were developed to estimate GFR in pediatric oncology patients, both of which did a better job at estimating mGFR than published equations.

  19. Glomerular hyperfiltration and metabolic syndrome: results from the FIrenze-BAgno A Ripoli (FIBAR) Study.

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    Monami, Matteo; Pala, Laura; Bardini, Gianluca; Francesconi, Paolo; Cresci, Barbara; Marchionni, Niccolò; Rotella, Carlo Maria; Mannucci, Edoardo

    2009-09-01

    Metabolic syndrome (MS) has been associated with microalbuminuria and kidney disease. In the present cohort study, different methods for the estimation of glomerular filtration rate (GFR) on the basis of serum creatinine were compared with respect to their association with MS and their predictive value for incident diabetes mellitus. The present analysis was performed on the cohort of subjects enrolled in the FIBAR study, a screening program for diabetes. GFR was estimated (eGFR) using three different methods: Cockroft-Gault (CG) formula, using actual body weight (CAW), CG formula using ideal body weight (CIW), and Modification of Diet in Renal Disease formula (M). The study was performed on 2,694 nondiabetic subjects, without history of renal insufficiency or serum creatinine at baseline >1.5 mg/dl. Mean follow-up was 27.8 +/- 11.5 months. Elevated eGFR, estimated with different methods, was associated with increased prevalence of most components of MS; however, an association between elevated clearance and MS was observed only when using CAW, which overestimates filtration in obese subjects. During follow-up, 40 new cases of diabetes were recorded (0.5/100 patient*years). After adjusting for age and sex, the HR (with 95% confidence intervals) for diabetes for patients in the highest quintile of eGFR was 1.14 [0.44-2.99], 0.89 [0.31-2.51], and 1.01 [0.42-2.41] for formula CAW, CIW, and M, respectively (all p > 0.7). Elevated eGFR, estimated through methods which do not produce a systematic overestimate in obese subjects, is not associated with the diagnosis of MS, and does not predict diabetes.

  20. Glomerular hyperfiltration and renal progression in children with autosomal dominant polycystic kidney disease.

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    Helal, Imed; Reed, Berenice; McFann, Kim; Yan, Xiang-Dong; Fick-Brosnahan, Godela M; Cadnapaphornchai, Melissa; Schrier, Robert W

    2011-10-01

    The purpose of this study was to determine whether glomerular hyperfiltration (GH) occurring early in autosomal dominant polycystic kidney disease (ADPKD) is indicative of more rapid disease progression in children. One hundred eighty children with ADPKD (ages 4 to 18 years) with normal renal function were examined by renal ultrasound. Renal volume was calculated using a standard formula for a modified ellipsoid. Creatinine clearance was calculated from serum creatinine and 24-hour urine creatinine. GH was defined as creatinine clearance ≥140 ml/min per 1.73 m(2). Thirty-two children had GH (mean age 11.4 ± 3.6 years) and 148 had normal renal function (mean age 10.8 ± 3.9 years). Patients with GH at baseline demonstrated an increased rate of total renal volume growth (β: rate of change = +19.3 ± 10.8 cm(3)/year) over 5 years compared with those without GH at baseline (β = -4.3 ± 7.7 cm(3)/year), P = 0.008. Those with GH at baseline experienced a faster decline in creatinine clearance in subsequent years (β = -5.0 ± 0.8 ml/min per 1.73 m(2) per year) compared with those without GH at baseline (β = +1.0 ± 0.4 ml/min per 1.73 m(2) per year), P children is associated with a significantly faster decline in renal function and higher rate of kidney enlargement over time. GH combined with the increased renal volume may therefore be used as an early marker for a more severe progression of ADPKD in children.

  1. Long-term outcome of anti-glomerular basement membrane antibody disease treated with immunoadsorption.

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    Peter Biesenbach

    Full Text Available Anti-glomerular basement membrane (GBM antibody disease may lead to acute crescentic glomerulonephritis with poor renal prognosis. Current therapy favours plasma exchange (PE for removal of pathogenic antibodies. Immunoadsorption (IAS is superior to PE regarding efficiency of antibody-removal and safety. Apart from anecdotal data, there is no systemic analysis of the long-term effects of IAS on anti-GBM-disease and antibody kinetics.To examine the long-term effect of high-frequency IAS combined with standard immunosuppression on patient and renal survival in patients with anti-GBM-disease and to quantify antibody removal and kinetics through IAS.Retrospective review of patients treated with IAS for anti-GBM-antibody disease confirmed by biopsy and/or anti-GBM-antibodies.University Hospital of Vienna, Austria.10 patients with anti-GBM-disease treated with IAS.Patient and renal survival, renal histology, anti-GBM-antibodies.Anti-GBM-antibodies were reduced by the first 9 IAS treatments (mean number of 23 to negative levels in all patients. Renal survival was 40% at diagnosis, 70% after the end of IAS, 63% after one year and 50% at the end of observation (mean 84 months, range 9 to 186. Dialysis dependency was successfully reversed in three of six patients. Patient survival was 90% at the end of observation.IAS efficiently eliminates anti-GBM-antibodies suggesting non-inferiority to PE with regard to renal and patient survival. Hence IAS should be considered as a valuable treatment option for anti-GBM-disease, especially in patients presenting with a high percentage of crescents and dialysis dependency due to an unusual high proportion of responders.

  2. Cystatin C in assessment of glomerular filtration rate in children and young adults suffering from cancer.

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    Barnfield, Mark C; Burniston, Maria T; Reid, Una; Graham, Alastair M; Henderson, Mick; Picton, Susan V

    2013-06-01

    The study objective was to establish the diagnostic efficacy of cystatin C in the assessment of glomerular filtration rate (GFR) in paediatric oncology patients by investigating the relationships between serum cystatin C, serum creatinine and isotope clearance and determining whether these relationships are different from those seen in a group of patients of similar age with renal disease. This was a cohort study in which patients were divided into two groups: group A comprised renal patients and group B comprised oncology patients. All patients were referred for isotopic GFR assessment as part of routine clinical management and concurrently also had assessments made of their serum creatinine and cystatin C levels, together with height and weight measurements. Reciprocals of cystatin C correlate well with isotopic GFR; correlation coefficients from linear regression were 0.83 and 0.66 for the renal and oncology groups, respectively. However, when GFR was assessed from serum creatinine and cystatin C, levels of agreement were still very high (95% levels of agreement: -33 and 31 ml/min/1.73 m for cystatin C and -46 and 30 ml/min/1.73 m for the Counahan serum creatinine estimate). Receiver-operator characteristic curve analysis demonstrated that cystatin C has improved diagnostic utility for identifying patients with GFRs both below normal (90 ml/min/1.73 m) and below the point at which chemotherapy dose reduction may be considered (60 ml/min/1.73 m). Levels of intrapatient variability were similar for both tracers. Cystatin C was shown to be a better indicator of renal function compared with serum creatinine in oncology patients as demonstrated by receiver-operator characteristic curve and Bland-Altman analyses; however, sensitivity of the tracer to mild reductions in GFR is still low.

  3. Correlation of Serum Cystatin C with Glomerular Filtration Rate in Patients Receiving Platinum-Based Chemotherapy

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    Ernesta Cavalcanti

    2016-01-01

    Full Text Available Objectives. Serum cystatin C seems to be an accurate marker of glomerular filtration rate (GFR compared to serum creatinine. The aim of this work was to explore the possibility of using serum cystatin C instead of serum creatinine to early predict renal failure in cancer patients who received platinum based chemotherapy. Design and Methods. Serum creatinine, serum cystatin C concentrations, and GFR were determined simultaneously in 52 cancer patients received carboplatin-based or cisplatin-based chemotherapy. Serum creatinine was assayed on Cobas C6000-Roche, serum cystatin C assay was performed on AIA 360-Tosoh, and GFR was determined in all patients, before the first cycle of chemotherapy and before the subsequent administrations. Results. In the overall series, for the prediction of a fall of GFR < 80 mL/min/1.73 m2, the AUC of the ROC curve for cystatin C was 0,667 and the best threshold was 1.135 mg/L (sensitivity 90.5%, specificity 61.1%. For a GFR fall < 60 mL/min/1.73 m2, the AUC of ROC curve for cystatin C was 74.3% and the best threshold was 1.415 mg/L (sensitivity 66.7%, specificity 73.2%. Conclusions. Baseline cystatin C values were not able to predict renal failure during subsequent treatment. In conclusion, serum cystatin C is not a reliable early marker to efficiently predict renal failure in patients receiving chemotherapy.

  4. [Cystatin C as a marker of glomerular filtration rate in patients with ovarian cancer].

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    Bodnar, Lubomir; Wcisło, Gabriel B; elichowski, Grzegorz; Raczka, Anna; Wańkowicz, Zofia; Szczylik, Cezary

    2008-04-01

    Cystatin C, a cysteine protease inhibitor, has been recommended as a new marker of glomerular filtration rate (GFR). THE AIM OF STUDY We investigated significance of cystatin C in assessment of GFR and its influence on overall survival (OS) in patients with ovarian cancer (OC). We prospectively included consecutive patients with OC, who after surgery were qualified to first line chemotherapy according to the following protocol: cisplatin 75 mg/m2 and 24-hour infusion of paclitaxel 135 mg/m2 every three weeks. We assessed: serum levels of creatinine (Cr), cystatin C (Cys C), creatinine clearance (ClCr) calculated from 24-hour urine collection, GFR estimated according to Cocroft-Gault (CG) and Modification Diet of Renal Disease (MDRD) formulas. Age median of 37 patients enrolled into this study was 54 years (range from 28 to 68). We noted correlation between cystatin C and CrCl (R Spearman= -0.36; p = 0.03). We did not state any correlation between Cys C and another markers of GFR as: serum creatinine, CG, MDRD. However, we observed correlation between Cys C and measured tumor mass seeing in spiral CT-scan (diameter more than 1 cm) after surgery (R Spearman = 0.4; p = 0.01) and serum level of marker CA 125 (R Spearman= 0.4; p = 0.03). We didn't find any statistical correlation between values of serum Cys C (using median's as cutoff values) in overall survival of our patients (log-rank test, p = 0.9). Serum cystatin C level in patient with ovarian cancer is both the poor marker of GFR and has not prognostic value in the course of cancer after surgery with further primary chemotherapy. The explanation of this phenomenon could rely on the presence of residual ovarian cancer.

  5. Permeation of macromolecules into the renal glomerular basement membrane and capture by the tubules

    Science.gov (United States)

    Lawrence, Marlon G.; Altenburg, Michael K.; Sanford, Ryan; Willett, Julian D.; Bleasdale, Benjamin; Ballou, Byron; Wilder, Jennifer; Li, Feng; Miner, Jeffrey H.; Berg, Ulla B.; Smithies, Oliver

    2017-01-01

    How the kidney prevents urinary excretion of plasma proteins continues to be debated. Here, using unfixed whole-mount mouse kidneys, we show that fluorescent-tagged proteins and neutral dextrans permeate into the glomerular basement membrane (GBM), in general agreement with Ogston's 1958 equation describing how permeation into gels is related to molecular size. Electron-microscopic analyses of kidneys fixed seconds to hours after injecting gold-tagged albumin, negatively charged gold nanoparticles, and stable oligoclusters of gold nanoparticles show that permeation into the lamina densa of the GBM is size-sensitive. Nanoparticles comparable in size with IgG dimers do not permeate into it. IgG monomer-sized particles permeate to some extent. Albumin-sized particles permeate extensively into the lamina densa. Particles traversing the lamina densa tend to accumulate upstream of the podocyte glycocalyx that spans the slit, but none are observed upstream of the slit diaphragm. At low concentrations, ovalbumin-sized nanoparticles reach the primary filtrate, are captured by proximal tubule cells, and are endocytosed. At higher concentrations, tubular capture is saturated, and they reach the urine. In mouse models of Pierson’s or Alport’s proteinuric syndromes resulting from defects in GBM structural proteins (laminin β2 or collagen α3 IV), the GBM is irregularly swollen, the lamina densa is absent, and permeation is increased. Our observations indicate that size-dependent permeation into the lamina densa of the GBM and the podocyte glycocalyx, together with saturable tubular capture, determines which macromolecules reach the urine without the need to invoke direct size selection by the slit diaphragm. PMID:28246329

  6. The relationship of serum and urinary laminin and glomerular filtration rate in diabetes mellitus

    International Nuclear Information System (INIS)

    Li Jianlin

    2002-01-01

    Objective: To observe the relationship of serum and urinary laminin and glomerular filtration rate (GFR) in diabetes mellitus. Methods: The level of serum and urinary laminin was measured by radioimmunoassay, GFR acquired by 99m Tc diethylenetriamine pentaacetic acid ( 99m Tc-DTPA), renal dynamic imaging in 75 diabetes mellitus and 42 normal subjects. Results: (1) The level of serum LN (136.30 ± 11.20 ng/ml) and urinary LN (31.76 ± 5.77 ng/ml) in diabetic nephropathy was significantly higher than that in diabetes without nephrosis group (P<0.05) and control group (P<0.01), the level of serum LN (126.54 ± 6.98 ng/ml) and urinary LN (26.27 ± 3.81 ng/ml) in diabetes without nephrosis group was significantly higher than that in control group (P<0.05); the GFR of diabetic nephropathy (78.84 ± 10.79 ng/ml) was significantly lower than that in diabetes without nephrosis group (P<0.05) and control group (P<0.01); the level of serum (131.49 ± 10.74 ng/ml) and urinary LN (29.05 ± 5.60 ng/ml) in diabetes mellitus was significantly higher than that in control group (P<0.05), but GFR was significantly lower than that in control group (P<0.05). (2) The value of GFR in diabetes mellitus lasted less than 1 year was higher than that of control group (P<0.05), but inverse in diabetes mellitus more than 10 years (P<0.05). (3) The level of serum and urinary LN had significantly negative correlation with GFR (P<0.01). Conclusion: LN may accelerates the alteration of GFR and causes microangiopathy of diabetic nephropathy. It may be an important indicator in the diagnosis of the early diabetic nephropathy

  7. Current use of equations for estimating glomerular filtration rate in Spanish laboratories.

    Science.gov (United States)

    Gràcia-Garcia, Sílvia; Montañés-Bermúdez, Rosario; Morales-García, Luis J; Díez-de Los Ríos, M José; Jiménez-García, Juan Á; Macías-Blanco, Carlos; Martínez-López, Rosalina; Ruiz-Altarejos, Joaquín; Ruiz-Martín, Guadalupe; Sanz-Hernández, Sonia; Ventura-Pedret, Salvador

    2012-07-17

    In 2006 the Spanish Society of Clinical Biochemistry and Molecular Pathology (SEQC) and the Spanish Society of Nephrology (S.E.N.) developed a consensus document in order to facilitate the diagnosis and monitoring of chronic kidney disease with the incorporation of equations for estimating glomerular filtration rate (eGFR) into laboratory reports. The current national prevalence of eGFR reporting and the degree of adherence to these recommendations among clinical laboratories is unknown. We administered a national survey in 2010-11 to Spanish clinical laboratories. The survey was through e-mail or telephone to laboratories that participated in the SEQC’s Programme for External Quality Assurance, included in the National Hospitals Catalogue 2010, including both primary care and private laboratories. A total of 281 laboratories answered to the survey. Of these, 88.2% reported on the eGFR, with 61.9% reporting on the MDRD equation and 31.6% using the MDRD-IDMS equation. A total of 42.5% of laboratories always reported serum creatinine values, and other variables only when specifically requested. Regarding the way results were presented, 46.2% of laboratories reported the exact numerical value only when the filtration rate was below 60mL/min/1.73m2, while 50.6% reported all values regardless. In 56.3% of the cases reporting eGFR, an interpretive commentary of it was enclosed. Although a high percentage of Spanish laboratories have added eGFR in their reports, this metric is not universally used. Moreover, some aspects, such as the equation used and the correct expression of eGFR results, should be improved.

  8. Serum C-reactive protein and thioredoxin levels in subjects with mildly reduced glomerular filtration rate

    Directory of Open Access Journals (Sweden)

    Ishimura Eiji

    2010-04-01

    Full Text Available Abstract Background Chronic kidney disease (CKD is a newly recognized high-risk condition for cardiovascular disease (CVD, and previous studies reported the changes in inflammation and oxidative stress in advanced stages of CKD. We compared the levels of serum biomarkers for inflammation and oxidative stress between subjects with normal and mildly reduced glomerular filtration rate (GFR. Methods The subjects were 182 participants of a health check-up program including those with normal (≥ 90 mL/min/1.73 m2, N = 79 and mildly reduced eGFR (60-89 mL/min/1.73 m2, N = 103 which was calculated based on serum creatinine, age and sex. We excluded those with reduced eGFR 2. No one had proteinuria. We measured serum levels of C-reactive protein (CRP and thioredoxin (TRX as the markers of inflammation and oxidative stress, respectively. Results As compared with subjects with normal eGFR, those with mildly reduced eGFR had increased levels of both CRP and TRX. Also, eGFR was inversely correlated with these biomarkers. The associations of eGFR with these biomarkers remained significant after adjustment for age and sex. When adjustment was done for eight possible confounders, CRP showed significant association with systolic blood pressure, high density lipoprotein cholesterol (HDL-C and non-HDL-C, whereas TRX was associated with sex significantly, and with eGFR and systolic blood pressure at borderline significance. Conclusions We showed the increased levels of CRP and TRX in subjects with mildly reduced eGFR. The eGFR-CRP link and the eGFR-TRX link appeared to be mediated, at least partly, by the alterations in blood pressure and plasma lipids in these subjects.

  9. Adjusted Anion Gap Is Associated with Glomerular Filtration Rate Decline in Chronic Kidney Disease.

    Science.gov (United States)

    Togawa, Akashi; Uyama, Satoko; Takanohashi, Seiko; Shimasaki, Megumi; Miyaji, Takehiko; Endo, Hiroyuki; Fujigaki, Yoshihide

    2013-01-01

    Metabolic acidosis is known to accelerate the progression of chronic kidney disease (CKD). However, whether undetermined anions as indicated by the adjusted anion gap (aAG) are associated with estimated glomerular filtration rate (eGFR) decline in patients with CKD is unclear. Data from 42 patients with CKD (baseline eGFR, 7.1-52.0 ml/min/ 1.73 m 2 ) without massive proteinuria (urinary protein-creatinine ratio, UPCR <3.5) were retrospectively analyzed. aAG was calculated from serum sodium, serum chloride, serum bicarbonate, serum albumin, serum potassium, serum calcium and serum phosphate. The association between the percentage of the 6-month change of eGFR (%ΔeGFR/6m) and aAG was examined. The mean baseline eGFR was 27.5 ± 11.1 ml/min/1.73 m 2 and the mean %ΔeGFR/6m was 13.8 ± 10.3. UPCR and aAG were 1.13 ± 0.93 and 9.48 ± 1.88, respectively. %ΔeGFR/6m was associated with aAG (r = 0.438, p < 0.005), but not with UPCR (r = 0.194, p = 0.218). In multivariate linear regression analyses, aAG remained significantly associated with %ΔeGFR/6m (β = 0.45, p < 0.01) after controlling for age, baseline eGFR, UPCR and HCO 3 - concentration. These data suggest that aAG appears to be associated with the progression of CKD. aAG might be an independent predictor of CKD progression.

  10. Performing a local barrier operation

    Science.gov (United States)

    Archer, Charles J; Blocksome, Michael A; Ratterman, Joseph D; Smith, Brian E

    2014-03-04

    Performing a local barrier operation with parallel tasks executing on a compute node including, for each task: retrieving a present value of a counter; calculating, in dependence upon the present value of the counter and a total number of tasks performing the local barrier operation, a base value, the base value representing the counter's value prior to any task joining the local barrier; calculating, in dependence upon the base value and the total number of tasks performing the local barrier operation, a target value of the counter, the target value representing the counter's value when all tasks have joined the local barrier; joining the local barrier, including atomically incrementing the value of the counter; and repetitively, until the present value of the counter is no less than the target value of the counter: retrieving the present value of the counter and determining whether the present value equals the target value.

  11. Exposure, Uptake, and Barriers

    Science.gov (United States)

    Baeza-Squiban, Armelle; Lanone, Sophie

    The nanotechnologies market is booming, e.g., in the food industry (powder additives, etc.) and in medical applications (drug delivery, prosthetics, diagnostic imaging, etc.), but also in other industrial sectors, such as sports, construction, cosmetics, and so on. In this context, with an exponential increase in the number of current and future applications, it is particularly important to evaluate the problem of unintentional (i.e., non-medical) exposure to manufactured nanoparticles (so excluding nanoparticles found naturally in the environment). In this chapter, we begin by discussing the various parameters that must be taken into account in any serious assessment of exposure to man-made nanoparticles. We then list the potential routes by which nanoparticles might enter into the organism, and outline the mechanisms whereby they could get past the different biological barriers. Finally, we describe the biodistribution of nanoparticles in the organism and the way they are eliminated.

  12. Countermeasures and barriers

    International Nuclear Information System (INIS)

    Petersen, Johannes

    2005-10-01

    In 1973 Haddon proposed ten strategies for reducing and avoiding damages based on a model of potential harmful energy transfer (Haddon, 1973). The strategies apply to a large variety of unwanted phenomena. Haddon's pioneering work on countermeasures has had a major influence on later thinking about safety. Considering its impact it is remarkable that the literature offers almost no discussions related to the theoretical foundations of Haddon's countermeasure strategies. The present report addresses a number of theoretical issues related to Haddon's countermeasure strategies, which are: 1) A reformulation and formalization of Haddon's countermeasure strategies. 2) An identification and description of some of the problems associated with the term 'barrier'. 3) Suggestions for a more precise terminology based on the causal structure of countermeasures. 4) Extending the scope of countermeasures to include sign-based countermeasures. (au)

  13. Countermeasures and barriers

    Energy Technology Data Exchange (ETDEWEB)

    Petersen, Johannes [Oersted - DTU, Automation, Kgs. Lyngby (Denmark)

    2005-10-01

    In 1973 Haddon proposed ten strategies for reducing and avoiding damages based on a model of potential harmful energy transfer (Haddon, 1973). The strategies apply to a large variety of unwanted phenomena. Haddon's pioneering work on countermeasures has had a major influence on later thinking about safety. Considering its impact it is remarkable that the literature offers almost no discussions related to the theoretical foundations of Haddon's countermeasure strategies. The present report addresses a number of theoretical issues related to Haddon's countermeasure strategies, which are: 1) A reformulation and formalization of Haddon's countermeasure strategies. 2) An identification and description of some of the problems associated with the term 'barrier'. 3) Suggestions for a more precise terminology based on the causal structure of countermeasures. 4) Extending the scope of countermeasures to include sign-based countermeasures. (au)

  14. Thames barrier (flood protection barriers on the Thames)

    International Nuclear Information System (INIS)

    Ilkovic, J.

    2005-01-01

    In this paper the flood protection barriers on the Thames are presented. The flood protection system on the Thames in 1984 was commissioned. During two decades this barrier was used 54 times against to the high water and 34 times against storm-sewage. There is installed buttress type hydroelectric power plant

  15. Measured glomerular filtration rate at dialysis initiation and clinical outcomes of Indian peritoneal dialysis patients

    Directory of Open Access Journals (Sweden)

    N Prasad

    2017-01-01

    Full Text Available The optimal time for dialysis initiation remains controversial. Studies have failed to show better outcomes with early initiation of hemodialysis; even a few had shown increased adverse outcomes including poorer survival. Few studies have examined the same in patients on peritoneal dialysis (PD. Measured glomerular filtration rate (mGFR not creatinine-based estimated GFR is recommended as the measure of kidney function in end-stage renal disease (ESRD patients. The objective of this observational study was to compare the outcomes of Indian patients initiated on PD with different residual renal function (RRF as measured by 24-h urinary clearance method. A total of 352 incident patients starting on chronic ambulatory PD as the first modality of renal replacement therapy were followed prospectively. Patients were categorized into three groups as per mGFR at the initiation of PD (≤5, >5–10, and> 10 ml/min/1.73 m2. Patient survival and technique survival were compared among the three groups. Patients with GFR of ≤5 ml/min/1.73 m2 (hazard ratio [HR] - 3.42, 95% confidence interval [CI] - 1.85–6.30, P = 0.000 and> 5–10 ml/min/1.73 m2 (HR - 2.16, 95% CI - 1.26–3.71, P = 0.005 had higher risk of mortality as compared to those with GFR of> 10 ml/min/1.73 m2. Each increment of 1 ml/min/1.73 m2 in baseline GFR was associated with 10% reduced risk of death (HR - 0.90, 95% CI - 0.85–0.96, P = 0.002. Technique survival was poor in those with an initial mGFR of ≤5 ml/min/1.73 m2 as compared to other categories. RRF at the initiation was also an important factor predicting nutritional status at 1 year of follow-up. To conclude, initiation of PD at a lower baseline mGFR is associated with poorer patient and technique survival in Indian ESRD patients.

  16. Cystatin C Is a Gender-Neutral Glomerular Filtration Rate Biomarker in Patients with Cirrhosis.

    Science.gov (United States)

    Mindikoglu, Ayse L; Opekun, Antone R; Mitch, William E; Magder, Laurence S; Christenson, Robert H; Dowling, Thomas C; Weir, Matthew R; Seliger, Stephen L; Howell, Charles D; Raufman, Jean-Pierre; Rana, Abbas; Goss, John A; Khaderi, Saira A; Vierling, John M

    2018-03-01

    Lower serum Cr levels in women as compared to men result in underestimation of renal dysfunction and lower model for end-stage liver disease-sodium scores leading to reduced access to liver transplantation in women compared to men with comparable hepatic dysfunction. The aim of this study was to determine the gender differences in serum Cr, cystatin C, and other endogenous glomerular filtration rate (GFR) biomarkers, measured and estimated GFR, Cr clearance, and Cr production rates. We measured GFR by iothalamate plasma clearance in 103 patients with cirrhosis and assessed gender differences in GFR, Cr clearance and production rate, serum Cr, cystatin C and other endogenous GFR biomarkers including beta-trace protein, beta-2 microglobulin, and dimethylarginines. Comparison of men and women showed significantly lower values for mean serum Cr (0.97 vs. 0.82 mg/dl, P = 0.023), and Cr production rate (13.37 vs. 11.02 mg/kg/day, P = 0.022). In contrast to the serum Cr and Cr production rate, men and women exhibited no significant differences in the means of serum cystatin C and other GFR biomarkers, measured GFR, GFR estimated using Cr-cystatin C GFR equation for cirrhosis, measured and estimated Cr clearances. After controlling for age, race, weight, height, and GFR, female gender remained associated with lower serum Cr levels (P = 0.003). Serum cystatin C levels were not associated with gender, age, race, weight, height, C-reactive protein, and history of hypothyroidism. Our results suggest that cystatin C and endogenous GFR biomarkers other than Cr, measured GFR, GFR estimated by Cr-cystatin C GFR equation for cirrhosis, measured and estimated Cr clearance minimized between-gender biases in accounting for renal function in patients with cirrhosis. Therefore, serum cystatin C should be measured as a complementary test to serum Cr when renal function is assessed in patients with cirrhosis, particularly in women and those with sarcopenia.

  17. The spectrum of glomerular diseases in a single center: A clinicopathological correlation

    Directory of Open Access Journals (Sweden)

    V Golay

    2013-01-01

    Full Text Available We report the spectrum of biopsy-proven glomerular disease (GD in a single center in Eastern India. Medical records of 666 patients with biopsy-proven GD over a period of 2 years from July 2010 to July 2012 were retrospectively analyzed. The clinical, laboratory, and histological data were recorded. All biopsy specimens were examined by the same pathologist with light and immunofluorescence microscopy. Electron microscopic analysis was performed only in selected cases. Histologic spectrum of various GDs was studied along with its correlation with the clinical and laboratory parameters. The clinical diagnosis was nephrotic syndrome (NS in 410 (61.56%, rapidly progressive renal failure/glomerulonephritis in 130 (19.52%, subnephrotic proteinuria/asymtomatic urinary abnormalities in 52 (7.81%, acute kidney injury/acute nephritic syndrome in 40 (6.01%, and macroscopic hematuria in 4 (0.6% patients. Male: Female ratio was 1.05; 27.92% (n = 186 were < 18 years, 68.47% (n = 456 were 18-59 years, and 3.6% (n = 24 were ≥ 60 years of age. The most common GD was minimal change disease (MCD (20.12%, n = 134; others were focal segmental glomerulosclerosis (FSGS (18.02%, n = 15.32%, lupus nephritis (LN (15.32%, n = 102, membranous nephropathy (MN (12.01%, n = 80, and IgA nephropathy (IgAN (8.11%, n = 54. Primary GD was present in 79.13% (n = 527 and common histologies were MCD (25.42%, FSGS (22.58%, MN (14.42%, and IgAN (10.25%. Secondary GD was present in 20.87% (n = 139, with the most common being LN (73.38%, n = 102. Among the NS (n = 410, the most common GD was MCD (31.46%, followed by FSGS (25.6%, MN (15.58%, LN (7.8%, IgAN (6.09%, and membranoproliferative glomerulonephritis (4.88%. FSGS was the most common primary GD in adults, MCD in children, and MN in the elderly patients. The spectrum of GD varies according to the area of study and changes over time. A biopsy registry is needed for documenting this variation.

  18. Aging and decreased glomerular filtration rate: An elderly population-based study.

    Directory of Open Access Journals (Sweden)

    Regina C R M Abdulkader

    Full Text Available Although a reduced glomerular filtration rate (GFR in old people has been attributed to physiologic aging, it may be associated with kidney disease or superimposed comorbidities. This study aims to assess the prevalence of decreased GFR in a geriatric population in a developing country and its prevalence in the absence of simultaneous diseases.This is a cross-sectional study of data from the Saúde, Bem-Estar e Envelhecimento cohort study (SABE study[Health, Well-Being and Aging], a multiple cohorts study. A multistage cluster sample composed of 1,253 individuals representative of 1,249,388 inhabitants of São Paulo city aged ≥60 years in 2010 was analyzed. The participants answered a survey on socio-demographic factors and health, had blood pressure measured and urine and blood samples collected. GFR was estimated and defined as decreased when 0.20 g/g.The prevalence of GFR <60 mL/min/1.73m2 was 19.3%. Individuals with GFR <60 mL/min/1.73m2 were older (75±1 versus 69±1 years, p<0.001, had lower schooling (18 versus 30% with complete 8-year basic cycle, p = 0.010, and higher prevalence of hypertension (82 versus 63%, p<0.001, diabetes (34 versus 26%, p = 0.021, cardiovascular disease (43 versus 24%, p<0.001 and kidney damage (35% versus 15%, p<0.001. Only 0.7% of the entire studied population had GFR <60 mL/min/1.73m2 without simultaneous diseases or kidney damage. Among the individuals with GFR <60 mL/min/1.73m2, 3.5% had neither renal damage nor associated comorbidities, whereas among those with GFR ≥60 mL/min/1.73m2, 11.0% had none of these conditions. Logistic regression showed that older age, cardiovascular disease and hypertension were associated with GFR<60 mL/min/1.73m2.Decreased GFR was highly prevalent among the geriatric population in a megalopolis of a developing country. It was rarely present without simultaneous chronic comorbidities or kidney damage.

  19. Immunohistochmical Study of Glomerular Mesengial Collagen IV Expression in Diabetic Balb/c Mice

    Directory of Open Access Journals (Sweden)

    M. Jalali

    2006-04-01

    Full Text Available Introduction & Objective: Extra-cellular matrix and basement membrane play important roles in many developmental phenamenon during development and after birth. Among the components of the basement membrane, collagen fibers specially type IV, are the most important part of this area. As kidney is one of the target organs in diabetes mellitus and diabetic nephropathy is a major cause of end stage-renal disease and result an increase in morbidity and mortality of effected individuals, therefore early diagnosis leads to better treatment. The aim of this investigation was to study the primary diagnostic parameters by special regards to collagen IV fibers.Materials & Methods: In this study, 24 male balb/c mice were divided into experimental and control groups. In experimental group, the beta cells of Langerhance were chemically destroyed by an injection of 160 mg/kg alloxan and subdivided in experimental groups 1 and 2. Controls were kept untreated. Experimental group 1and 2 were sacrified 8 and 16 weeks after treatment with alloxan respectively. The same procedure was performed for control group. Immunohistochmical studies were carried out using monocolonal antibody against collagen type IV in Glomeruli. In addition, using morphometrical and stereological methods the volume of the glumerles was compared in all groups.Results: Our finding showed that in experimental groups with special regards in 16 weeks diabetic mice, the rate of collagen type IV in basement membrane around the parietal layer of Bowman capsule, mesangial cells and endothelium of capillary in glomerules increased significantly compared to controls and experimental group 1 (p<0.05, while there was not a significant difference among experimental group 2 and controls. Our data also revealed that the number of mesangial cells as well as glomerular volume increased significantly in experimental 2 (4.635±0.289×106µm3 compared to experimental 1 (3.504±0.189×106µm3 and controls (3.422

  20. Effect of benazepril, robenacoxib and their combination on glomerular filtration rate in cats.

    Science.gov (United States)

    King, Jonathan N; Panteri, Alessandro; Graille, Melanie; Seewald, Wolfgang; Friton, Gabriele; Desevaux, Cyril

    2016-06-23

    Combined use of angiotensin-converting enzyme inhibitors and nonsteroidal anti-inflammatory drugs may induce acute kidney injury in humans, especially when combined with diuretics. The objective of this investigation was to evaluate the effects of benazepril, robenacoxib and their combination in healthy cats. In each of two studies (study 1 followed by study 2), 32 healthy cats were randomised to one of four groups (n = 4 male and 4 female cats per group) in a parallel-group design. The groups received orally once daily for 7 days either placebo (control group), benazepril, robenacoxib or benazepril plus robenacoxib. In study 2, all groups received in addition 0.5 mg/kg furosemide twice daily by subcutaneous injection for 7 days. Benazepril, robenacoxib and their combination were well tolerated as evidenced from lack of clinical signs and no negative effects on body weight, feed consumption and clinical chemistry, haematology and urinalysis variables. The primary endpoint of the study was the glomerular filtration rate (GFR), which was estimated from the plasma clearance of iohexol. In the absence of furosemide, GFR was significantly higher in cats receiving the combination of benazepril plus robenacoxib compared to the other three groups, and was also significantly higher in females receiving only benazepril compared to the control. Administration of furosemide induced diuresis, reduced GFR and activated the renin-aldosterone-angiotensin system, evidenced from increased plasma renin activity and plasma aldosterone concentrations. Compared to the control group in cats treated with furosemide, GFR was increased by benazepril (females only) but decreased by robenacoxib (males only). Benazepril, robenacoxib and their combination significantly inhibited the increase in plasma aldosterone induced by furosemide. The combination of benazepril and robenacoxib was well tolerated and either increased or had a neutral effect on GFR in healthy cats without or with

  1. Existing creatinine-based equations overestimate glomerular filtration rate in Indians.

    Science.gov (United States)

    Kumar, Vivek; Yadav, Ashok Kumar; Yasuda, Yoshinari; Horio, Masaru; Kumar, Vinod; Sahni, Nancy; Gupta, Krishan L; Matsuo, Seiichi; Kohli, Harbir Singh; Jha, Vivekanand

    2018-02-01

    Accurate estimation of glomerular filtration rate (GFR) is important for diagnosis and risk stratification in chronic kidney disease and for selection of living donors. Ethnic differences have required correction factors in the originally developed creatinine-based GFR estimation equations for populations around the world. Existing equations have not been validated in the vegetarian Indian population. We examined the performance of creatinine and cystatin-based GFR estimating equations in Indians. GFR was measured by urinary clearance of inulin. Serum creatinine was measured using IDMS-traceable Jaffe's and enzymatic assays, and cystatin C by colloidal gold immunoassay. Dietary protein intake was calculated by measuring urinary nitrogen appearance. Bias, precision and accuracy were calculated for the eGFR equations. A total of 130 participants (63 healthy kidney donors and 67 with CKD) were studied. About 50% were vegetarians, and the remainder ate meat 3.8 times every month. The average creatinine excretion were 14.7 mg/kg/day (95% CI: 13.5 to 15.9 mg/kg/day) and 12.4 mg/kg/day (95% CI: 11.2 to 13.6 mg/kg/day) in males and females, respectively. The average daily protein intake was 46.1 g/day (95% CI: 43.2 to 48.8 g/day). The mean mGFR in the study population was 51.66 ± 31.68 ml/min/1.73m 2 . All creatinine-based eGFR equations overestimated GFR (p < 0.01 for each creatinine based eGFR equation). However, eGFR by CKD-EPI Cys was not significantly different from mGFR (p = 0.38). The CKD-EPI Cys exhibited lowest bias [mean bias: -3.53 ± 14.70 ml/min/1.73m 2 (95% CI: -0.608 to -0.98)] and highest accuracy (P 30 : 74.6%). The GFR in the healthy population was 79.44 ± 20.19 (range: 41.90-134.50) ml/min/1.73m 2 . Existing creatinine-based GFR estimating equations overestimate GFR in Indians. An appropriately powered study is needed to develop either a correction factor or a new equation for accurate assessment of kidney function in the

  2. Tumor necrosis factor-alpha-induced reduction of glomerular filtration rate in rats with fulminant hepatic failure.

    Science.gov (United States)

    Wang, Jing-Bo; Wang, Dong-Lei; Wang, Hai-Tao; Wang, Zhao-Han; Wen, Ying; Sun, Cui-Ming; Zhao, Yi-Tong; Wu, Jian; Liu, Pei

    2014-07-01

    The mechanism of renal failure during fulminant hepatic failure (FHF) or end-stage of liver disease is not fully understood. The present study aims to delineate the mechanisms of decreased glomerular filtration rate (GFR) in acute hepatic failure. A rat model of renal insufficiency in severe liver injury was established by lipopolysaccharide (LPS) plus D-galactosamine (GalN) exposure. GFR was evaluated by continuous infusion of fluorescein isothiocyanate-inulin with implanted micro-osmotic pumps. GalN/LPS intoxication resulted in severe hepatocyte toxicity as evidenced by liver histology and biochemical tests, whereas renal morphology remained normal. GFR was reduced by 33% of the controls 12 h after GalN/LPS exposure, accompanied with a decreased serum sodium levels, a marked increase in serum TNF-α and ET-1 levels as well as significantly upregulated renal type 1 inositol 1,4,5-trisphosphate receptor (IP3R1) expression. The upregulated IP3R1 expression was abrogated by the treatment of anti-TNF-α antibodies, but not by 2-aminoethoxydiphenylborate (2-APB), which blocks the inositol 1,4,5-trisphosphate signaling pathway. Treatments with either TNF-α antibodies or 2-APB also significantly improved the compromised GFR, elevated serum urea nitrogen and creatinine levels, and reversed the decrease in glomerular inulin space and the increase in glomerular calcium content in GalN/LPS-exposed rats. The extent of acute liver injury as reflected by serum ALT levels was much more attenuated by anti-TNF-α antibodies than by 2-APB. Liver histology further confirmed that anti-TNF-α antibodies conferred better protection than 2-APB in GalN/LPS-exposed rats. LPS-elicited TNF-α over-production is responsible for decreased GFR through IP3R1 overexpression, and the compromised GFR resulted in the development of acute renal failure in rats with FHF.

  3. Predictors of estimated glomerular filtration rate progression, stabilization or improvement after chronic renal impairment in HIV-positive individuals

    DEFF Research Database (Denmark)

    Ryom, Lene; Mocroft, Amanda; Kirk, Ole

    2017-01-01

    GFR defining CRI, and changes were grouped into improvement (>+10 ml/min per 1.73 m), stabilization (-10 to +10 ml/min per 1.73 m) and progression (polynomial regression models assessed odds of better eGFR outcomes after CRI, assuming that eGFR improvement is better than......OBJECTIVES: The objectives of this analysis were to investigate predictors of progression, stabilization or improvement in estimated glomerular filtration rate (eGFR) after development of chronic renal impairment (CRI) in HIV-positive individuals. DESIGN: Prospective observational study. METHODS...

  4. Transcutaneous measurement of glomerular filtration rate in conscious laboratory animals: state of the art and future perspectives

    Science.gov (United States)

    Friedemann, Jochen; Schock-Kusch, Daniel; Shulhevich, Yury

    2017-02-01

    Transcutaneous measurement of Glomerular Filtration Rate (tGFR) is now frequently used in preclinical in vivo animal studies. tGFR allows consecutive measurements on the same animal, including multiple measurements on a daily basis. A description of the measurement device and its many applications, along with examples from the recent literature will be given. We will highlight the fields of interest in which the system is used and give an overview about its performance versus endogenous and other exogenous methods of GFR measurement. A special focus will be put on the precision of tGFR compared to standard measurements employed in the research setting.

  5. Application of Kohonen neural networks for the non-morphological distinction between glomerular and tubular renal disease.

    Science.gov (United States)

    Van Biesen, W; Sieben, G; Lameire, N; Vanholder, R

    1998-01-01

    A Kohonen topological map is an artificial intelligence system of the connectionist school (neural networks). The map learns the typical features of the subclasses in the learning set by means of a shortest Euclidean distance algorithm, after which self-adaptation of the neurons occurs. By its ability of self-organization and generalization, a Kohonen map is useful for pattern recognition, and its application in the medical field as an aid for decision making seems promising. This study describes the use of a Kohonen topological mapping system in the classification of renal diseases as being glomerular or tubular on basis of clinical characteristics and laboratory results. Forty-one parameters from 75 patients were retrospectively retrieved and used to train four different Kohonen maps of 10 x 10 neurons. For reference diagnostic classification, we referred to the results of the light-microscopic examination. The classification of the patients by the four different Kohonen networks was compared to the classification by a rule-based system and by three nephrologists. We also developed a 'hybrid' decision system that makes a classification on basis of the opinion of the four networks and that of the rule-based system. The results show that a Kohonen map is capable of classifying the patients as having glomerular or tubular disease with a higher sensitivity and predictive value than the nephrologists and the rule-based system, and that the best classification was performed by the hybrid system: sensitivity and predictive value for the diagnosis 'glomerular' respectively 100 and 88% for the network with the most adequate results, 90 and 83% for the nephrologists, 90 and 95% for the rule-based system, and 95 and 96% for the hybrid system; sensitivity and predictive value for the diagnosis 'tubular' respectively 50 and 100% for the neural networks, 31 and 45% for the nephrologists, 81 and 68% for the rule-based system, and 87 and 82% for the hybrid system). We conclude

  6. Renal uptake of dimercaptosuccinic acid and glomerular filtration rate in chronic nephropathy at angiotensin converting enzyme inhibition

    International Nuclear Information System (INIS)

    Kamper, A.L.; Thomsen, H.S.; Nielsen, S.L.; Strandgaard, S.; Herlev Hospital

    1990-01-01

    Glomerular filtration rate (GFR) and renal uptake of dimercaptosuccinic acid (DMSA) were measured in 31 patients with progressive chronic nephropathy before and immediately after the start of treatment with angiotensin converting enzyme (ACE) inhibitor in order to control adverse effects on kidney function. Scintigrams of the kidneys showed an unaltered distribution of DMSA during treatment. GFR estimated by 51 Cr-EDTA plasma clearance fell by 14% (P 99m Tc-DMSA increased by 10% (P<0.01). It is concluded that DMSA in chronic renal failure is mainly taken up by the tubular cells from the peritubular capillaries since the uptake was unaffected by the acute decrease in GFR. (orig.)

  7. A prospective study of glomerular filtration rate and arterial blood pressure in insulin-dependent diabetics with diabetic nephropathy

    DEFF Research Database (Denmark)

    Parving, H H; Smidt, U M; Friisberg, B

    1981-01-01

    Glomerular filtration rate (GFR, single bolus 51Cr-EDTA technique), serum creatinine, proteinuria and arterial blood pressure have been measured prospectively in 14 young onset insulin-dependent diabetics selected by of persistent proteinuria (greater than 0.5 g/day) secondary to diabetic...... nephropathy. Twelve of the 14 patients had normal serum creatinine levels. None of the patients received antihypertensive treatment. During the mean observation period of 26 months (range 23 to 33 months) GFR decreased from 107 to 87 ml/min/1.73 m2 (p less than 0.001), serum creatinine remained unchanged: 107...

  8. Risk Stratification by 24-Hour Ambulatory Blood Pressure and Estimated Glomerular Filtration Rate in 5322 Subjects From 11 Populations

    DEFF Research Database (Denmark)

    Boggia, José; Thijs, Lutgarde; Li, Yan

    2013-01-01

    point, and stroke, ABP(24) added 0.35%, 1.17%, and 1.00% to the risk already explained by cohort, sex, age, body mass index, smoking and drinking, previous cardiovascular disease, diabetes mellitus, and antihypertensive drug treatment. Adding eGFR explained an additional 0.13%, 0.09%, and 0......No previous study addressed whether in the general population estimated glomerular filtration rate (eGFR [Chronic Kidney Disease Epidemiology Collaboration formula]) adds to the prediction of cardiovascular outcome over and beyond ambulatory blood pressure. We recorded health outcomes in 5322...

  9. Verification on the use of the Inoue method for precisely determining glomerular filtration rate in Philippine pediatrics

    Science.gov (United States)

    Magcase, M. J. D. J.; Duyan, A. Q.; Carpio, J.; Carbonell, C. A.; Trono, J. D.

    2015-06-01

    The objective of this study is to validate the Inoue method so that it would be the preferential choice in determining glomerular filtration rate (GFR) in Philippine pediatrics. The study consisted of 36 patients ranging from ages 2 months to 19 years old. The subjects used were those who were previously subjected to in-vitro method. The scintigrams of the invitro method was obtained and processed for split percentage uptake and for parameters needed to obtain Inoue GFR. The result of this paper correlates the Inoue GFR and In-vitro method (r = 0.926). Thus, Inoue method is a viable, simple, and practical technique in determining GFR in pediatric patients.

  10. Comparison of inulin, iothalamate, and /sup 99m/Tc-DTPA for measurement of glomerular filtration rate

    International Nuclear Information System (INIS)

    Barbour, G.L.; Crumb, C.K.; Boyd, C.M.; Reeves, R.D.; Rastogi, S.P.; Patterson, R.M.

    1976-01-01

    Clearances of inulin, 125 I-iothalamate, and /sup 99m/Tc-Sn-DTPA were measured simultaneously in five mongrel dogs exhibiting a wide range of glomerular filtration rates (GFR). Standard constant-infusion inulin clearance was compared to radionuclide clearances after subcutaneous injection of the emitters mixed with aqueous epinephrine. All three substances were found to have virtually identical clearances. The accuracy, accessibility, low cost, low radiation hazard, and short half-life of /sup 99m/Tc-Sn-DTPA make it an excellent substance for measuring GFR. The subcutaneous technique offers an accuracy comparable to the more difficult constant-infusion method

  11. Informal export barriers and poverty

    OpenAIRE

    Porto, Guido G.

    2004-01-01

    The author investigates the poverty impacts of informal export barriers like transport costs, cumbersome customs practices, costly regulations, and bribes. He models these informal barriers as export taxes that distort the efficient allocation of resources. In low-income agricultural economies, this distortion lowers wages and household agricultural income, thereby leading to higher pover...

  12. Barriers to Women in Science

    Science.gov (United States)

    Butler, Rosemary

    2013-01-01

    The Presiding Officer of the National Assembly for Wales, Rosemary Butler AM, has put the issue of barriers to women in public life at the top of the political agenda in Wales. She has held sessions with women across Wales to find out what those barriers are and how they can be tackled. On International Women's Day in February, she invited…

  13. Seismic waves and seismic barriers

    Science.gov (United States)

    Kuznetsov, S. V.

    2011-05-01

    The basic idea of seismic barrier is to protect an area occupied by a building or a group of buildings from seismic waves. Depending on nature of seismic waves that are most probable in a specific region, different kinds of seismic barriers are suggested. For example, vertical barriers resembling a wall in a soil can protect from Rayleigh and bulk waves. The FEM simulation reveals that to be effective, such a barrier should be (i) composed of layers with contrast physical properties allowing "trapping" of the wave energy inside some of the layers, and (ii) depth of the barrier should be comparable or greater than the considered seismic wave length. Another type of seismic barrier represents a relatively thin surface layer that prevents some types of surface seismic waves from propagating. The ideas for these barriers are based on one Chadwick's result concerning non-propagation condition for Rayleigh waves in a clamped half-space, and Love's theorem that describes condition of non-existence for Love waves. The numerical simulations reveal that to be effective the length of the horizontal barriers should be comparable to the typical wavelength.

  14. Structure information from fusion barriers

    Indian Academy of Sciences (India)

    It is shown that the analysis of fusion barrier distributions is not always an unambiguous test or a 'fingerprint' of the structure information of the colliding nuclei. Examples are presented with same fusion barrier distributions for nuclei having different structures. The fusion excitation functions for 16O+208Pb, using the coupled ...

  15. BARRIERS OF STRATEGIC ALLIANCES ORGANIZATION

    Directory of Open Access Journals (Sweden)

    Vladislav M. Sannikov

    2014-01-01

    Full Text Available General barriers of organization of different types of strategic alliances have beenconsidered in the article. There are several recommendations for overcoming themin cases of international alliances, and in case of work in one state. The article also identified goals and tasks of single coordination center of alliance to overcome organization barriers.

  16. Organizational Barriers to Transition: Summary.

    Science.gov (United States)

    Haynes, John; Justice, Thomas I., Ed.

    This study sought to identify the barriers that negatively impact the ability of disabled youth to successfully make a transition from school into employment and a quality adult life, and sought to specifically define organizational disincentives to successful transition. Current research is reviewed relating to organizational barriers to…

  17. Glomerular filtration values obtained with 99mTc-DTPA v/s measurements of creatinine Clearance and calculation of the filtered glomerular using the Schwartz formula in a pediatric population

    International Nuclear Information System (INIS)

    Opazo, Claudio; Gutierrez, Elisa; Zamorano, Julio; Troncoso, TM

    2005-01-01

    We compare glomerular filtration rate by DTPA Renogram (DTPA-GFR) with creatinine clearance (CC) and Glomerular filtration rate from Schwartz formula (Schwartz-GFR). The need for using (DTPA-GFR) method raised from the practical difficulties in getting an accurate (CC) in pediatric population. From Sep-2001 to May-2005, 48 patients aged 1month to 18 years, underwent (DTPA-GFR) and (Schwartz-GFR). 18 had also (CC). Comparison were made among these measurements also accounting for age groups. We found a better correlation between (DTPA-GFR) and (CC) Pearson = 0,895. (Schwartz)/(CC) comparison showed a slightly lower correlation Pearson = 0,857. The worst correlation was found comparing (DTPA-GFR)/(Schwartz-GFR) in children < 3 yr Pearson = 0,560. As we found a better correlation between (DTPA-GFR)/(CC) than (DTPA-GFR)/(Schwartz-GFR), DTPA-GFR could be considered reliable method in evaluating renal function in children having difficulties to get a Creatinine Clearance (au)

  18. Epistemological barriers to radical behaviorism.

    Science.gov (United States)

    O'Donohue, W T; Callaghan, G M; Ruckstuhl, L E

    1998-01-01

    The historian and philosopher of science Gaston Bachelard proposed the concept of epistemological barriers to describe the intellectual challenges encountered by scientists in their work. In order to embrace novel ways of approaching a problem in science, scientists must overcome barriers or obstacles posed by their prior views. For example, Einsteinian physics presents scientists with claims that space is curved and that time and space are on the same continuum. We utilize Bachelard's concept of epistemological barriers to describe the differences between the intellectual journeys students pursuing advanced studies face when attempting to accept cognitive psychology or radical behaviorism. We contend that the folk psychological beliefs that students typically hold when entering these studies pose less challenge to cognitive psychology than to radical behaviorism. We also suggest that these barriers may also partly be involved in the problematic exegesis that has plagued radical behaviorism. In close, we offer some suggestions for dealing with these epistemological barriers.

  19. Epistemological barriers to radical behaviorism

    Science.gov (United States)

    O'Donohue, William T.; Callaghan, Glenn M.; Ruckstuhl, L. E.

    1998-01-01

    The historian and philosopher of science Gaston Bachelard proposed the concept of epistemological barriers to describe the intellectual challenges encountered by scientists in their work. In order to embrace novel ways of approaching a problem in science, scientists must overcome barriers or obstacles posed by their prior views. For example, Einsteinian physics presents scientists with claims that space is curved and that time and space are on the same continuum. We utilize Bachelard's concept of epistemological barriers to describe the differences between the intellectual journeys students pursuing advanced studies face when attempting to accept cognitive psychology or radical behaviorism. We contend that the folk psychological beliefs that students typically hold when entering these studies pose less challenge to cognitive psychology than to radical behaviorism. We also suggest that these barriers may also partly be involved in the problematic exegesis that has plagued radical behaviorism. In close, we offer some suggestions for dealing with these epistemological barriers. PMID:22478314

  20. Barriers for recess physical activity

    DEFF Research Database (Denmark)

    Pawlowski, Charlotte Skau; Tjørnhøj-Thomsen, Tine; Schipperijn, Jasper

    2014-01-01

    . This was verified by a thematic analysis of transcripts from the open discussions and go-along interviews. RESULTS: The most frequently identified barriers for both boys and girls were weather, conflicts, lack of space, lack of play facilities and a newly-found barrier, use of electronic devices. While boys......BACKGROUND: Many children, in particular girls, do not reach the recommended amount of daily physical activity. School recess provides an opportunity for both boys and girls to be physically active, but barriers to recess physical activity are not well understood. This study explores gender...... differences in children's perceptions of barriers to recess physical activity. Based on the socio-ecological model four types of environmental barriers were distinguished: natural, social, physical and organizational environment. METHODS: Data were collected through 17 focus groups (at 17 different schools...