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Sample records for abnormal glomerular filtration

  1. Glomerular filtration rate

    MedlinePlus

    ... 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 ...

  2. Glomerular Filtration Barrier Assembly: An insight

    PubMed Central

    Arif, Ehtesham; Nihalani, Deepak

    2016-01-01

    A glomerulus is the network of capillaries that resides in the Bowman’s capsule that functions as a filtration unit of kidney. The glomerular function ensures that essential plasma proteins are retained in blood and the filtrate is passed on as urine. The glomerular filtration assembly is composed of three main cellular barriers that are critical for the ultrafiltration process, the fenestrated endothelium, glomerular basement membrane and highly specialized podocytes. The podocytes along with their specialized junctions “slit diaphragm” form the basic backbone of this filtration assembly. The presence of high amounts of protein in urine a condition commonly referred as proteinuria indicates a defective glomerular filtration barrier. Various glomerular disorders including Nephrotic syndrome are characterized by significant alteration in the structure of podocytes that is associated with prolonged increase in the glomerular permeability leading to heavy proteinuria. Recent identification of proteins that are specifically localized at the slit diaphragm whose mutations and knockouts are known to result in loss of renal function has significantly advanced our understanding of the molecular makeup of this filtration assembly. The present review is an effort to summarize the recent developments in this field and highlight our understanding of the glomerular filtration barrier assembly.

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

    NASA Astrophysics Data System (ADS)

    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.

  4. Structural basis for reduced glomerular filtration capacity in nephrotic humans.

    PubMed Central

    Drumond, M C; Kristal, B; Myers, B D; Deen, W M

    1994-01-01

    Previous studies have established that in a variety of human glomerulopathies the reduced glomerular filtration rate (GFR) is due to a marked lowering of the ultrafiltration coefficient (Kf). To identify the factors which lower Kf, we measured the filtering surface area per glomerulus, filtration slit frequency, basement membrane thickness, and GFR and its determinants in patients with minimal change and membraneous nephropathies and in age-matched healthy controls. Overall values of Kf for the two kidneys were calculated from GFR, renal plasma flow rate, systemic colloid osmotic pressure, and three assumed values for the transcapillary pressure difference. "Experimental" values of the glomerular hydraulic permeability (kexp) were then calculated from Kf, glomerular filtering surface area, and estimates of the total number of nephrons of the two kidneys. Independent estimates of the glomerular hydraulic permeability (kmodel) were obtained using a recent mathematical model that is based on analyses of viscous flow through the various structural components of the glomerular capillary wall. Individual values of basement membrane thickness and filtration slit frequency were used as inputs in this model. The results indicate that the reductions of Kf in both nephropathies can be attributed entirely to reduced glomerular hydraulic permeability. The mean values of kexp and kmodel were very similar in both disorders and much smaller in the nephrotic groups than in healthy controls. There was good agreement between kexp and kmodel for any given group of subjects. It was shown that, in both groups of nephrotics, filtration slit frequency was a more important determinant of the water flow resistance than was basement membrane thickness. The decrease in filtration slit frequency observed in both disorders caused the average path length for the filtrate to increase, thereby explaining the decreased hydraulic permeability. Images PMID:8083359

  5. Optimized robust plasma sampling for glomerular filtration rate studies.

    PubMed

    Murray, Anthony W; Gannon, Mark A; Barnfield, Mark C; Waller, Michael L

    2012-09-01

    In the presence of abnormal fluid collection (e.g. ascites), the measurement of glomerular filtration rate (GFR) based on a small number (1-4) of plasma samples fails. This study investigated how a few samples will allow adequate characterization of plasma clearance to give a robust and accurate GFR measurement. A total of 68 nine-sample GFR tests (from 45 oncology patients) with abnormal clearance of a glomerular tracer were audited to develop a Monte Carlo model. This was used to generate 20 000 synthetic but clinically realistic clearance curves, which were sampled at the 10 time points suggested by the British Nuclear Medicine Society. All combinations comprising between four and 10 samples were then used to estimate the area under the clearance curve by nonlinear regression. The audited clinical plasma curves were all well represented pragmatically as biexponential curves. The area under the curve can be well estimated using as few as five judiciously timed samples (5, 10, 15, 90 and 180 min). Several seven-sample schedules (e.g. 5, 10, 15, 60, 90, 180 and 240 min) are tolerant to any one sample being discounted without significant loss of accuracy or precision. A research tool has been developed that can be used to estimate the accuracy and precision of any pattern of plasma sampling in the presence of 'third-space' kinetics. This could also be used clinically to estimate the accuracy and precision of GFR calculated from mistimed or incomplete sets of samples. It has been used to identify optimized plasma sampling schedules for GFR measurement. PMID:22825040

  6. Glomerular basement membrane composition and the filtration barrier

    PubMed Central

    2011-01-01

    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. PMID:21327778

  7. Preliminary Findings of Serum Creatinine and Estimated Glomerular Filtration Rate (eGFR) in Adolescents with Intellectual Disabilities

    ERIC Educational Resources Information Center

    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…

  8. Estimation of glomerular filtration rate in cynomolgus monkeys (Macaca fascicularis).

    PubMed

    Iwama, Ryosuke; Sato, Tsubasa; Sakurai, Ken; Takasuna, Kiyoshi; Ichijo, Toshihiro; Furuhama, Kazuhisa; Satoh, Hiroshi

    2014-10-01

    To estimate the glomerular filtration rate (GFR) in cynomolgus monkeys (Macaca fascicularis), a three-blood-sample method using iodixanol was assessed in comparison with the conventional multisample strategy using inulin. Iodixanol and inulin were coadministered intravenously 40 mg I/kg and 50 mg/kg, respectively, to male monkeys, followed by blood collection 60, 90 and 120 min later. A close correlation (r=0.96) was noted between the GFR values estimated by both methods. In clinically healthy monkeys, the basal values were determined to be 3.06 ± 0.50 ml/min/kg. This is the first report, suggesting that serum clearance of iodixanol is a ready-to-use tool for a screening the GFR in monkeys, although it is necessary to perform a more longitudinal study using animals with reduced renal function. PMID:24998395

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

    PubMed

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

    2015-01-01

    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. PMID:26274567

  10. Maternal Glomerular Filtration Rate in Pregnancy and Fetal Size

    PubMed Central

    Morken, Nils-Halvdan; Travlos, Gregory S.; Wilson, Ralph E.; Eggesbø, Merete; Longnecker, Matthew P.

    2014-01-01

    Background The relationship of maternal glomerular filtration rate (GFR) in pregnancy to fetal size needs to be better characterized as it impacts an ongoing debate about confounding effect of maternal GFR in investigations of important environmental contaminants. We aimed to characterize the size of the association between maternal GFR and infant birth weight. Materials and Methods A sub-cohort of 953 selected women (470 women with and 483 women without preeclampsia) in the Norwegian Mother and Child Cohort (MoBa), recruited during 2003–2007 were analyzed. GFR in the second trimester was estimated based on plasma creatinine. Birth weight was ascertained from the Medical Birth Registry of Norway. Multivariate linear regression was used to evaluate the association between maternal GFR in second trimester (estimated by the Cockroft-Gault [GFR-CG] and the modification of diet in renal disease [GFR-MDRD] formulas) and infant birth weight. Partial correlation coefficients were also calculated. Results Maternal GFR-CG (β: 0.73 g/ml/min, p = 0.04) and GFR-MDRD (β: 0.83 g/ml/min, p = 0.04) were associated with infant birth weight in models adjusted for maternal weight in kilograms, preeclampsia, and gestational age at delivery (days). Partial correlation coefficients for the association between infant birth weight and GFR were 0.07 for both formulas. Although the birth weight-GFR association was stronger among the women with preeclampsia, the difference from women without preeclampsia was not statistically significant. Conclusion These data support an association between GFR during pregnancy and infant birth weight, and indicate that GFR may confound selected epidemiologic associations. PMID:25003331

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

    SciTech Connect

    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.

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

    PubMed

    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. PMID:23147865

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

    SciTech Connect

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

    1985-07-01

    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 /sup 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.

  14. Complement-Mediated Dysfunction of Glomerular Filtration Barrier Accelerates Progressive Renal Injury

    PubMed Central

    Abbate, Mauro; Zoja, Carla; Corna, Daniela; Rottoli, Daniela; Zanchi, Cristina; Azzollini, Nadia; Tomasoni, Susanna; Berlingeri, Silvia; Noris, Marina; Morigi, Marina; Remuzzi, Giuseppe

    2008-01-01

    Intrarenal complement activation leads to chronic tubulointerstitial injury in animal models of proteinuric nephropathies, making this process a potential target for therapy. This study investigated whether a C3-mediated pathway promotes renal injury in the protein overload model and whether the abnormal exposure of proximal tubular cells to filtered complement could trigger the resulting inflammatory response. Mice with C3 deficiency were protected to a significant degree against the protein overload–induced interstitial inflammatory response and tissue damage, and they had less severe podocyte injury and less proteinuria. When the same injury was induced in wild-type (WT) mice, antiproteinuric treatment with the angiotensin-converting enzyme inhibitor lisinopril reduced the amount of plasma protein filtered, decreased the accumulation of C3 by proximal tubular cells, and protected against interstitial inflammation and damage. For determination of the injurious role of plasma-derived C3, as opposed to tubular cell–derived C3, C3-deficient kidneys were transplanted into WT mice. Protein overload led to the development of glomerular injury, accumulation of C3 in podocytes and proximal tubules, and tubulointerstitial changes. Conversely, when WT kidneys were transplanted into C3-deficient mice, protein overload led to a more mild disease and abnormal C3 deposition was not observed. These data suggest that the presence of C3 increases the glomerular filtration barrier's susceptibility to injury, ultrafiltered C3 contributes more to tubulointerstitial damage induced by protein overload than locally synthesized C3, and local C3 synthesis is irrelevant to the development of proteinuria. It is speculated that therapies targeting complement combined with interventions to minimize proteinuria would more effectively prevent the progression of renal disease. PMID:18354030

  15. Calcium Mediates Glomerular Filtration through Calcineurin and mTORC2/Akt Signaling

    PubMed Central

    Bracken, Christina; Matthews, Douglas; O'Brien, Stephen; Schiavi, Susan; Wawersik, Stefan

    2011-01-01

    Alterations to the structure of the glomerular filtration barrier lead to effacement of podocyte foot processes, leakage of albumin, and the development of proteinuria. To better understand the signaling pathways involved in the response of the glomerular filtration barrier to injury, we studied freshly isolated rat glomeruli, which allows for the monitoring and pharmacologic manipulation of early signaling events. Administration of protamine sulfate rapidly damaged the isolated glomeruli, resulting in foot process effacement and albumin leakage. Inhibition of calcium channels and chelation of extracellular calcium reduced protamine sulfate-induced damage, suggesting that calcium signaling plays a critical role in the initial stages of glomerular injury. Calcineurin inhibitors (FK506 and cyclosporine A) and the cathepsin L inhibitor E64 all inhibited protamine sulfate-mediated barrier changes, which suggests that calcium signaling acts, in part, through calcineurin- and cathepsin L-dependent cleavage of synaptopodin, a regulator of actin dynamics. The mTOR inhibitor rapamycin also protected glomeruli, demonstrating that calcium signaling has additional calcineurin-independent components. Furthermore, activation of Akt through mTOR had a direct role on glomerular barrier integrity, and activation of calcium channels mediated this process, likely independent of phosphoinositide 3-kinase. Taken together, these results demonstrate the importance of calcium and related signaling pathways in the structure and function of the glomerular filtration barrier. PMID:21784900

  16. Podocyte-specific knockout of myosin 1e disrupts glomerular filtration.

    PubMed

    Chase, Sharon E; Encina, Christina V; Stolzenburg, Lindsay R; Tatum, Arthur H; Holzman, Lawrence B; Krendel, Mira

    2012-10-01

    Myosin 1e (myo1e) is an actin-dependent molecular motor that plays an important role in kidney functions. Complete knockout of myo1e in mice and Myo1E mutations in humans are associated with nephrotic syndrome and focal segmental glomerulosclerosis. In this paper, we tested the hypothesis that myo1e is necessary for normal functions of glomerular visceral epithelial cells (podocytes) using podocyte-targeted knockout of myo1e. Myo1e was selectively knocked out in podocytes using Cre-mediated recombination controlled by the podocin promoter. Myo1e loss from podocytes resulted in proteinuria, podocyte foot process effacement, and glomerular basement membrane disorganization. Our findings indicate that myo1e expression in podocytes is necessary for normal glomerular filtration and that podocyte defects are likely to represent the primary pathway leading to glomerular disease associated with Myo1E mutations. PMID:22811491

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

    NASA Technical Reports Server (NTRS)

    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.

  18. Maintenance of Glomerular Filtration Barrier Integrity Requires Laminin α5

    PubMed Central

    Goldberg, Seth; Adair-Kirk, Tracy L.; Senior, Robert M.

    2010-01-01

    Mutation of the mouse laminin α5 gene results in a variety of developmental defects, including defects in kidney structure and function. Whereas the total absence of laminin α5 results in breakdown of the glomerular basement membrane (GBM) and failed glomerular vascularization, a hypomorphic Lama5 mutation (the Lama5neo allele) results in proteinuria, hematuria, polycystic kidney disease (PKD), and death 3 to 4 weeks after birth. Here, we examined the role of podocyte-derived laminin α5 via podocyte-specific inactivation of Lama5 and podocyte-specific rescue of the Lama5neo mutation. Podocyte-specific inactivation of Lama5 resulted in varying degrees of proteinuria and rates of progression to nephrotic syndrome. The GBM of proteinuric mice appeared thickened and “moth-eaten,” and podocyte foot processes became effaced. Podocyte-specific restoration of laminin α5 production using two distinct strategies in Lama5neo/neo mice resulted in the resolution of proteinuria, hematuria, and PKD. These results suggest that the development of normal GBM structure and function requires podocyte-derived laminin α5 during and after glomerulogenesis and present a unique mechanism for the pathogenesis of PKD in these mice. PMID:20150535

  19. Somatostatin analogue, octreotide, reduces increased glomerular filtration rate and kidney size in insulin-dependent diabetes

    SciTech Connect

    Serri, O.; Beauregard, H.; Brazeau, P.; Abribat, T.; Lambert, J.; Harris, A.; Vachon, L. Sandoz Canada Inc., Dorval, Quebec )

    1991-02-20

    To determine whether treatment with a somatostatin analogue can reduce kidney hyperfiltration and hypertrophy in insulin-dependent diabetes mellitus, the authors studied 11 patients with insulin-dependent diabetes mellitus and glomerular hyperfiltration. The patients were assigned randomly to receive continuous subcutaneous infusion of either octreotide, 300 {mu}g/24 h (five patients) or placebo (six patients) for 12 weeks. At baseline, mean glomerular filtration rate and mean total kidney volume were not significantly different in the two groups. However, after 12 weeks of treatment, the mean glomerular filtration rate was significantly lower in the octreotide group than in the placebo group. Furthermore, the mean total kidney volume was significantly lower after treatment in the octreotide group than in the placebo group. Glycemic control did not change significantly in either group. They conclude that subcutaneous infusion of octreotide for 12 weeks reduces increased glomerular filtration rate and kidney size in patients with insulin-dependent diabetes mellitus despite the fact that glycemic control remains unchanged.

  20. Par3A is dispensable for the function of the glomerular filtration barrier of the kidney.

    PubMed

    Koehler, Sybille; Tellkamp, Frederik; Niessen, Carien M; Bloch, Wilhelm; Kerjaschki, Dontscho; Schermer, Bernhard; Benzing, Thomas; Brinkkoetter, Paul T

    2016-07-01

    Polarity signaling through the atypical PKC (aPKC)-Par polarity complex is essential for the development and maintenance of the podocyte architecture and the function of the glomerular filtration barrier of the kidney. To study the contribution of Par3A in this complex, we generated a novel Pard3 podocyte-specific knockout mouse model by targeting exon 6 of the Pard3 gene. Genetic deletion of Pard3a did not impair renal function, neither at birth nor later in life. Even challenging the animals did not result in glomerular disease. Despite its well-established role in aPKC-mediated signaling, Par3A appears to be dispensable for the function of the glomerular filtration barrier. Moreover, its homolog Pard3b, and not Pard3a, is the dominant Par3 gene expressed in podocytes and found at the basis of the slit diaphragm, where it partially colocalizes with podocin. In conclusion, Par3A function is either dispensable for slit diaphragm integrity, or compensatory mechanisms and a high redundancy of the different polarity proteins, including Par3B, Lgl, or PALS1, maintain the function of the glomerular filtration barrier, even in the absence of Par3A. PMID:27122542

  1. The effect of intravesical pressure on glomerular filtration rate in patients with myelomeningocele.

    PubMed

    Steinhardt, G F; Goodgold, H M; Samuels, L D

    1988-11-01

    Numerous investigators have demonstrated the development of hydronephrosis and renal deterioration in patients with myelomeningocele who have high pressure bladders. By drawing blood at sequential intervals during 99mtechnetium-diethylenetriaminepentaacetic acid renal scanning we are able to generate nuclide clearance curves that correlate well with glomerular filtration rate. Renal scanning is done most frequently with the bladder catheterized and left to gravity drainage. By filling the bladder under manometric control to a pressure of 35 to 40 cm. water we have followed routine scanning with continued blood sampling to generate nuclide clearance at low and high bladder pressures. In 5 myelomeningocele patients so studied we found consistent and significant decreases in glomerular filtration rate at high bladder pressures. PMID:3184307

  2. Assessment of glomerular filtration rate measurement with plasma sampling: a technical review.

    PubMed

    Murray, Anthony W; Barnfield, Mark C; Waller, Michael L; Telford, Tania; Peters, A Michael

    2013-06-01

    This article reviews available radionuclide-based techniques for glomerular filtration rate (GFR) measurement, focusing on clinical indications for GFR measurement, ideal GFR radiopharmaceutical tracer properties, and the 2 most common tracers in clinical use. Methods for full, 1-compartment, and single-sample renal clearance characterization are discussed. GFR normalization and the role of GFR measurement in chemotherapy dosing are also considered. PMID:23658207

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

    PubMed

    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. PMID:26154927

  4. Association of estimated glomerular filtration rate with 24-h urinalysis and stone composition.

    PubMed

    Moreira, Daniel M; Friedlander, Justin I; Hartman, Christopher; Gershman, Boris; Smith, Arthur D; Okeke, Zeph

    2016-08-01

    The aim of this study is to determine the association of estimated glomerular filtration rate (eGFR) with 24-h urine analysis and stone composition. We performed a retrospective review of 1060 stone formers with 24-h urinalysis, of which 499 had stone composition analysis available. Comparisons of baseline patient characteristics and urinary abnormalities across eGFR groups (<60, 60-89.9, ≥90 mL/min/1.73 m(2)) were performed using Fisher's exact test for categorical data and analysis of variance for continuous variables. Analyses of 24-h urinalysis and stone composition across eGFR groups were performed using linear regression with eGFR groups as a continuous variable to evaluate trends. Of the 1060 patients in the study, 595 (56 %) were males. The mean age was 53.8 years. A total of 38 (4 %), 77 (7 %), and 945 (89 %) patients had eGFR <60, 60-89.9, and ≥90 mL/min/1.73 m(2), respectively. Lower eGFR was associated with older age, lower body-mass index, and female gender (all P < 0.05). Lower eGFR was also associated with lower urinary volume, calcium, citrate, uric acid, sodium, magnesium, phosphorus, sulfate, and creatinine on both univariable and multivariable analyses, adjusted for demographics, comorbidities and medication use (all P < 0.05). The prevalence of hypocitraturia and hypomagnesuria was associated with decreased eGFR, while hypercalciuria, hyperoxaluria, hyperuricosuria and hyperphosphaturia were associated with higher eGFR (all P < 0.05). Stone composition was similar across eGFR groups (all P > 0.05). In conclusion, lower eGFR was associated with lower excretion of urinary elements in a routine 24-h urinalysis, but similar stone composition. PMID:26573808

  5. Increased tubuloglomerular feed-back mediated suppression of glomerular filtration during acute volume expansion in rats.

    PubMed Central

    Davis, J M; Häberle, D A; Kawata, T; Schmitt, E; Takabatake, T; Wohlfeil, S

    1988-01-01

    1. Volume expansion is currently believed to change the intrinsic properties of the juxtaglomerular apparatus such that the sensitivity of the tubuloglomerular feedback (TGF) mechanism is reduced, thus allowing glomerular filtration rate, and hence salt and water excretion, to rise. Recent studies conflict with this view and indeed the older literature reveals that the rise in glomerular filtration rate (GFR) under these conditions is far more modest than would be expected if TGF control were eliminated. 2. To investigate this problem, TGF control of filtration rate was examined by measuring single-nephron glomerular filtration rate (SNGFR) during loop of Henle perfusion at varying rates in rats under control conditions, after acute, moderate (4% of body weight), iso-oncotic volume expansion and in rats treated with antibodies to atrial natriuretic peptide (ANP) prior to the acute volume expansion. 3. With TGF control of filtration interrupted by filtrate collection from the proximal tubule, SNGFR in the expanded rats was massively increased compared with controls, although SNGFR measured in the distal tubule, and hence with TGF control intact, was only modestly increased, as was whole-kidney filtration rate. Loop perfusion at increasing rates up to 30 nl min-1 progressively decreased SNGFR in controls, and in the expanded rats the range over which control was exerted extended up to 60-80 nl min-1. For changes in loop flow around the spontaneous operating point, the sensitivity of the TGF mechanism, defined as delta SNGFR/delta loop flow, was similar in both groups. Treatment of rats with ANP antibodies prior to volume expansion substantially blunted the changes in renal salt and water excretion and the increase in SNGFR seen in the absence of loop perfusion. 4. These results are not consistent with a diminution of TGF function after volume expansion, rather with an enhancement. The latter is best accounted for by vasodilation of preglomerular resistance vessels on

  6. Acute effects of antiglomerular basement membrane antibody on the process of glomerular filtration in the rat.

    PubMed Central

    Blantz, R C; Wilson, C B

    1976-01-01

    Nehron filtration rate (sngfr) and the factors controlling filtration were examined before and with 60 min of the intravenous infusion of 225-450 mug of antiglomerular basement membrane antibody (AGBM Ab) (greater than 50% antigenic saturation) in plasma-expanded (2.5% body wt) Munich-Wistar rats. Pressures in glomerular capillaries (PG) and bowman's space (Pt) were measured with a servo-nulling device, systemic (piA) and efferent arteriolar oncotic pressures (piE) were measured by microprotein methods, and nephron plasma flow (rpf) and sngfr were measured by micropuncture techniques in both control and post-AGBM Ab conditions in each rat. The sngfr fell from 52.7+/-2.9 to 24.1+/-1.9 nl/min per g kidney wt (n = 7, P less than 0.001). Both afferent and efferent arteriolar resistances increased and rpf fell from 221+/-25 to 90+/-9 nl/min per g kidney wt (P less than 0.001) but the hydrostatic pressure gradient across the glomerular membrane deltaP = PG - Pt) increased from 37+/- 1 to 50+/-2 mm Hg (P less than 0.001). The increase in deltaP and a numerical decrease in piA both acted to maintain sngfr after AGBM Ab and effectively nullified the influence of decreased rpf upon sngfr. The mean effective filtration pressure (EFP = deltaP - pi) increased from 14+/-2 to 30+/-3 mm Hg (P less than 0.001) while sngfr decreased. The major and critical reason for this reduction in sngfr was a decrease in the glomerular permeability coefficient from 0.077+/-0.017 to 0.014+/-0.001 nl/s per g kidney wt per mm Hg P less than 0.001) where sngfr=EFP-LpA. Images PMID:61207

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

    SciTech Connect

    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 approx.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.

  8. Alport syndrome: its effects on the glomerular filtration barrier and implications for future treatment

    PubMed Central

    Savige, Judy

    2014-01-01

    The glomerular filtration barrier comprises a fenestrated capillary endothelium, glomerular basement membrane and podocyte slit diaphragm. Over the past decade we have come to realise that permselectivity depends on size and not necessarily charge, that the molecular sieve depends on the podocyte contractile apparatus and is highly dynamic, and that protein uptake by proximal tubular epithelial cells stimulates signalling and the production of transcription factors and inflammatory mediators. Alport syndrome is the second commonest monogenic cause of renal failure after autosomal dominant polycystic kidney disease. Eighty per cent of patients have X-linked disease caused by mutations in the COL4A5 gene. Most of these result in the replacement of the collagen IV α3α4α5 network with the α1α1α2 heterotrimer. Affected membranes also have ectopic laminin and increased matrix metalloproteinase levels, which makes them more susceptible to proteolysis. Mechanical stress, due to the less elastic membrane and hypertension, interferes with integrin-mediated podocyte–GBM adhesion. Proteinuria occurs when urinary levels exceed tubular reabsorption rates, and initiates tubulointerstitial fibrosis. The glomerular mesangial cells produce increased TGFβ and CTGF which also contribute to glomerulosclerosis. Currently there is no specific therapy for Alport syndrome. However treatment with angiotensin converting enzyme (ACE) inhibitors delays renal failure progression by reducing intraglomerular hypertension, proteinuria, and fibrosis. Our greater understanding of the mechanisms underlying the GBM changes and their consequences in Alport syndrome have provided us with further novel therapeutic targets. PMID:25107927

  9. Shroom3 contributes to the maintenance of the glomerular filtration barrier integrity

    PubMed Central

    Yeo, Nan Cher; O’Meara, Caitlin C.; Bonomo, Jason A.; Veth, Kerry N.; Tomar, Ritu; Flister, Michael J.; Drummond, Iain A.; Bowden, Donald W.; Freedman, Barry I.; Lazar, Jozef; Link, Brian A.

    2015-01-01

    Genome-wide association studies (GWAS) identify regions of the genome correlated with disease risk but are restricted in their ability to identify the underlying causative mechanism(s). Thus, GWAS are useful “roadmaps” that require functional analysis to establish the genetic and mechanistic structure of a particular locus. Unfortunately, direct functional testing in humans is limited, demonstrating the need for complementary approaches. Here we used an integrated approach combining zebrafish, rat, and human data to interrogate the function of an established GWAS locus (SHROOM3) lacking prior functional support for chronic kidney disease (CKD). Congenic mapping and sequence analysis in rats suggested Shroom3 was a strong positional candidate gene. Transferring a 6.1-Mb region containing the wild-type Shroom3 gene significantly improved the kidney glomerular function in FHH (fawn-hooded hypertensive) rat. The wild-type Shroom3 allele, but not the FHH Shroom3 allele, rescued glomerular defects induced by knockdown of endogenous shroom3 in zebrafish, suggesting that the FHH Shroom3 allele is defective and likely contributes to renal injury in the FHH rat. We also show for the first time that variants disrupting the actin-binding domain of SHROOM3 may cause podocyte effacement and impairment of the glomerular filtration barrier. PMID:25273069

  10. Detection of decreased glomerular filtration rate in intensive care units: serum cystatin C versus serum creatinine

    PubMed Central

    2014-01-01

    Background Detecting impaired glomerular filtration rate (GFR) is important in intensive care units (ICU) in order to diagnose acute kidney injuries and adjust the dose of renally excreted drugs. Whether serum Cystatin C (SCysC) may better reflect glomerular filtration rate than serum creatinine (SCr) in the context of intensive care medicine is uncertain. Methods We compared the performance of SCysC and SCr as biomarkers of GFR in 47 critically ill patients (median SOFA (Sepsis-related Organ Failure Assessment) score of 5) for whom GFR was measured by a reference method (urinary clearance of iohexol). Results Mean Iohexol clearance averaged 96 ± 54 mL/min and was under 60 mL/min in 28% of patients. Mean SCr and SCysC concentrations were 0.70 ± 0.33 mg/dL and 1.26 ± 0.61 mg/L, respectively. Area under the ROC curve for a GFR threshold of 60 mL/min was 0.799 and 0.942 for SCr and SCysC, respectively (p = 0.014). Conclusions We conclude that ScysC significantly outperfoms SCr for the detection of an impaired GFR in critically ill patients. Trial registration ClinicalTrials.gov: B7072006347 PMID:24410757

  11. Serum cystatin is not a marker of glomerular filtration rate in pregnancy

    PubMed Central

    Bramham, Kate; Makanjuola, David; Hussein, Wael; Cafful, Debra; Shehata, Hassan

    2009-01-01

    The role of cystatin C (Cys-C) as a marker of glomerular filtration rate (GFR) in pregnancy is undetermined. Measurements of Cys-C and creatinine (Cr) were taken at 14–17+6, 18–23+6, 27–31+6 weeks' gestation, at delivery and 2–6 weeks postpartum in a prospective observational study of 27 women. There was no difference between Cys-C levels in early and late second trimester, but they were significantly higher in early third trimester (P < 0.001) than second trimester, despite no concurrent increase in Cr. Cys-C was also significantly higher at delivery than at all other times in pregnancy (P < 0.001) and fell to postpartum values higher than second trimester measurements (P < 0.01), but lower than delivery (P<0.001). In conclusion, changes in Cys-C may be influenced by pregnancy-related changes in glomerular filtration and therefore we would advise against their use as a marker of GFR in pregnancy.

  12. Linkage Analysis of Glomerular Filtration Rate in American Indians: The Strong Heart Family Study

    PubMed Central

    Mottl, Amy K.; Vupputuri, Suma; Cole, Shelley A.; Almasy, Laura; Göring, Harald HH; Diego, Vincent P.; Laston, Sandra; Franceschini, Nora; Shara, Nawar; Lee, Elisa T.; Best, Lyle G.; Fabsitz, Richard R.; MacCluer, Jean W.; Umans, Jason G.; North, Kari E.

    2009-01-01

    American Indians have a disproportionately high rate of kidney disease likely due to a combination of increased environmental and genetic risk factors. In an attempt to localize genes influencing kidney disease risk factors, we performed a genome wide scan of estimated glomerular filtration rate on participants of the Strong Heart Family Study. Over 3 600 men and women from 13 American Indian tribes were recruited from 3 centers (Arizona, North and South Dakota, Oklahoma). Using SOLAR 2.1.2, multipoint variance component linkage analysis was performed in each center as well as the entire cohort after controlling for center effects. Two modeling strategies were utilized: model 1 incorporated age, sex and interaction terms and model 2 additionally controlled for diabetic status, systolic and diastolic blood pressure, body mass index, low density lipoproteins, high density lipoproteins, triglycerides and smoking status. Significant evidence for linkage in Arizona lay on 12p12.2 at 39cM nearest marker D12S310 (LOD=3.5). Additional loci with suggestive evidence for linkage were detected at 1p36.31 (LOD=2.0–2.3), 2q33.3 (LOD=1.8) and 9q34.2 (LOD=2.4). No significant evidence for additive interaction with diabetes, hypertension or obesity was noted. In conclusion, we found evidence for linkage of a quantitative trait locus influencing estimated glomerular filtration rate to a region of chromosome 12p in a large cohort of American Indians. PMID:18854848

  13. Glomerular filtration and tubular secretion of MAG-3 in the rat kidney

    SciTech Connect

    Mueller-Suur, R.M.; Mueller-Suur, C. )

    1989-12-01

    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. Odd E. Hanssen and the Hanssen method for measurement of single-nephron glomerular filtration rate.

    PubMed

    Aukland, K

    2001-09-01

    In the middle of the twentieth century, the suspicion that deep and superficial nephrons might serve different functions created a demand for measurement of single-nephron glomerular filtration rate (SNGFR). Rather unexpectedly, the answer came from Odd E. Hanssen (1917-1964), a Norwegian physician working on his own in the Department of Pathological Anatomy, University of Oslo, with minimal support and no interaction with renal physiologists. In 1963, after nearly 10 years of work, he presented the ferrocyanide method, allowing simultaneous estimates of SNGFR in a large number of nephrons in all layers of the kidney. This review first describes his early visions of the method and the elaborate and extremely time-consuming studies in mice to verify the technique. As a byproduct came valuable information on the relationship between nephron size and SNGFR, glomerular intermittency, and the emptying of the tubules on filtration stop. Hanssen died from a cerebral hemorrhage in 1964, and for several years the method seemed entirely forgotten. Fortunately, Andrew Baines took up the use of ferrocyanide in 1963-1964 while working on his thesis in Toronto, but his first publication came in 1969 from Saclay, France, in collaboration with Christian de Rouffignac. Modifications allowing determination of absolute SNGFR were worked out by de Rouffignac and by Jaime Coehlo in New York. Thereafter, the "Hanssen method" spread rapidly, and in the early 1980s about 50 reports had been published from 17 laboratories in 9 countries. The distribution of SNGFR in mammals, birds, and fish was described, as well as the response to water and salt loads, vasoactive substances, hormones, varying perfusion pressure, blood loss, etc. Finally, after mentioning two recent methods inspired by the Hanssen technique but using other filtration markers, the review concludes that most of our present knowledge on SNGFR distribution and regulation has been obtained by the method developed by Hanssen 40

  15. Associations of estimated glomerular filtration rate and albuminuria with mortality and renal failure by sex: a meta-analysis

    PubMed Central

    Nitsch, Dorothea; Grams, Morgan; Sang, Yingying; Black, Corri; Cirillo, Massimo; Djurdjev, Ognjenka; Iseki, Kunitoshi; Jassal, Simerjot K; Kimm, Heejin; Kronenberg, Florian; Øien, Cecilia M; Levin, Adeera; Woodward, Mark; Hemmelgarn, Brenda R

    2013-01-01

    Objective To assess for the presence of a sex interaction in the associations of estimated glomerular filtration rate and albuminuria with all-cause mortality, cardiovascular mortality, and end stage renal disease. Design Random effects meta-analysis using pooled individual participant data. Setting 46 cohorts from Europe, North and South America, Asia, and Australasia. Participants 2 051 158 participants (54% women) from general population cohorts (n=1 861 052), high risk cohorts (n=151 494), and chronic kidney disease cohorts (n=38 612). Eligible cohorts (except chronic kidney disease cohorts) had at least 1000 participants, outcomes of either mortality or end stage renal disease of ≥50 events, and baseline measurements of estimated glomerular filtration rate according to the Chronic Kidney Disease Epidemiology Collaboration equation (mL/min/1.73 m2) and urinary albumin-creatinine ratio (mg/g). Results Risks of all-cause mortality and cardiovascular mortality were higher in men at all levels of estimated glomerular filtration rate and albumin-creatinine ratio. While higher risk was associated with lower estimated glomerular filtration rate and higher albumin-creatinine ratio in both sexes, the slope of the risk relationship for all-cause mortality and for cardiovascular mortality were steeper in women than in men. Compared with an estimated glomerular filtration rate of 95, the adjusted hazard ratio for all-cause mortality at estimated glomerular filtration rate 45 was 1.32 (95% CI 1.08 to 1.61) in women and 1.22 (1.00 to 1.48) in men (Pinteraction<0.01). Compared with a urinary albumin-creatinine ratio of 5, the adjusted hazard ratio for all-cause mortality at urinary albumin-creatinine ratio 30 was 1.69 (1.54 to 1.84) in women and 1.43 (1.31 to 1.57) in men (Pinteraction<0.01). Conversely, there was no evidence of a sex difference in associations of estimated glomerular filtration rate and urinary albumin-creatinine ratio with end stage renal

  16. A method for estimating the glomerular filtration rate in conscious monkeys.

    PubMed

    Satoh, Hiroshi; Nomiya, Nana; Imai, Daiki; Sato, Shigeru; Sakurai, Ken; Takasuna, Kiyoshi; Furuhama, Kazuhisa

    2016-02-01

    To establish a method for estimating the glomerular filtration rate (GFR) in conscious monkeys, the radiographic contrast medium iodixanol and the standard agent inulin were coadministered as tracers to male cynomolgus monkeys (Macaca fascicularis) as a bolus injection; blood was collected after 60, 90 and 120 min. An equation based on a single-blood-sample method derived from Jacobsson's formula was prepared using the data from healthy and saline- and gentamicin-treated monkeys by a multisample strategy with iodixanol. The GFR using the equation with iodixanol was in agreement with that from the multisample method with inulin or iodixanol. When the GFR decreased to more than 60% of the basal reference level, serum creatinine concentrations tended to increase, whereas serum blood urea nitrogen concentrations fluctuated. The results suggest that the single-sample-blood method with iodixanol is a practical tool for estimating the monkey GFR in a toxicological research setting therefore minimizing animal sufferings. PMID:25994107

  17. An overview of glomerular filtration rate testing in dogs and cats.

    PubMed

    Von Hendy-Willson, Vanessa E; Pressler, Barrak M

    2011-05-01

    Determination of glomerular filtration rate (GFR) is a valuable, yet underused, diagnostic tool for evaluating renal function in dogs and cats. This article first reviews the hormonal and hemodynamic factors which contribute to GFR, followed by a description of considerations when selecting a pharmacokinetic model and methods of animal-to-animal standardization. The best-characterized existing GFR markers, including creatinine, radiolabeled markers, and iohexol, are reviewed in depth, as well as alternative but lesser used techniques. A weighted means analysis of reported GFR measurements in healthy dogs and cats and a review of selected studies that have examined GFR alterations in animals with naturally occurring and experimental diseases provide the reader with preliminary guidelines on expected GFR results in these species and disease conditions. PMID:20541957

  18. Experience with the cumulative integral method for measurement of glomerular filtration rate *

    PubMed Central

    Hurley, R. Morrison; Drummond, Keith N.

    1974-01-01

    The glomerular filtration rate (GFR) was estimated using 125I-iothalamate by the cumulative integral method in 95 subjects — 16 normal subjects and 79 patients with suspected or proved renal disease. This method is accurate, simple to perform and theoretically sound. It minimizes errors due to transit time and bladder storage. The normal range of GFR was determined to be 71 ± 10 (two standard deviations) ml/min/m2. In 66 patients serum creatinine levels were compared with the GFR value expressed per square metre. For any given serum creatinine level there is a wide range of GFR values. A serum creatinine value in the normal range, i.e. between 0.7 and 1.3 mg/dl, cannot be used to predict the patient's GFR. The micro blood sampling technique makes this method particularly useful in infants. PMID:4834526

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

    PubMed Central

    2014-01-01

    Background 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 (<1 μm) cellular and extracellular elements. Methods Here we have combined three different advanced electron microscopic techniques that cover multiple orders of magnitude of volume sampled, with a novel staining methodology (Lanthanum Dysprosium Glycosaminoglycan adhesion, or LaDy GAGa), to determine the structural basis of these two additional layers. Serial Block Face Scanning Electron Microscopy (SBF-SEM) was used to generate a 3-D image stack with a volume of a 5.3 x 105 μm3 volume of a whole kidney glomerulus (13% of 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. Results 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. Conclusions These images demonstrate that the

  20. Outcome Assessment of a Computer-Animated Model for Learning about the Regulation of Glomerular Filtration Rate

    ERIC Educational Resources Information Center

    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)…

  1. Blood Lead Level and Measured Glomerular Filtration Rate in Children with Chronic Kidney Disease

    PubMed Central

    Abraham, Alison G.; Navas-Acien, Ana; Guallar, Eliseo; Weaver, Virginia M.; Furth, Susan L.

    2013-01-01

    Background: The role of environmental exposure to lead as a risk factor for chronic kidney disease (CKD) and its progression remains controversial, and most studies have been limited by a lack of direct glomerular filtration rate (GFR) measurement. Objective: We evaluated the association between lead exposure and GFR in children with CKD. Methods: In this cross-sectional study, we examined the association between blood lead levels (BLLs) and GFR measured by the plasma disappearance of iohexol among 391 participants in the Chronic Kidney Disease in Children (CKiD) prospective cohort study. Results: Median BLL and GFR were 1.2 µg/dL and 44.4 mL/min per 1.73 m2, respectively. The average percent change in GFR for each 1-µg/dL increase in BLL was –2.1 (95% CI: –6.0, 1.8). In analyses stratified by CKD diagnosis, the association between BLL and GFR was stronger among children with glomerular disease underlying CKD; in this group, each 1-µg/dL increase in BLL was associated with a –12.1 (95% CI: –22.2, –1.9) percent change in GFR. In analyses stratified by anemia status, each 1-µg/dL increase in BLL among those with and without anemia was associated with a –0.3 (95% CI: –7.2, 6.6) and –4.6 (95% CI: –8.9, –0.3) percent change in GFR, respectively. Conclusions: There was no significant association between BLL and directly measured GFR in this relatively large cohort of children with CKD, although associations were observed in some subgroups. Longitudinal analyses are needed to examine the temporal relationship between lead and GFR decline, and to further examine the impact of underlying cause of CKD and anemia/hemoglobin status among patients with CKD. PMID:23694739

  2. Cystatin C and beta2-microglobulin: markers of glomerular filtration in critically ill children

    PubMed Central

    Herrero-Morín, José David; Málaga, Serafín; Fernández, Nuria; Rey, Corsino; Diéguez, María Ángeles; Solís, Gonzalo; Concha, Andrés; Medina, Alberto

    2007-01-01

    Introduction Parameters allowing regular evaluation of renal function in a paediatric intensive care unit (PICU) are not optimal. The aim of the present study was to analyse the utility of serum cystatin C and beta2-microglobulin (B2M) in detecting decreased glomerular filtration rate in critically ill children. Methods This was a prospective, observational study set in an eight-bed PICU. Twenty-five children were included. The inverses of serum creatinine, cystatin C, and B2M were correlated with creatinine clearance (CrC) using a 24-hour urine sample and CrC estimation by Schwartz formula (Schwartz). The diagnostic value of serum creatinine, cystatin C, and B2M to identify a glomerular filtration rate under 80 ml/minute per 1.73 m2 was evaluated using receiver operating characteristic (ROC) curve analysis. Results Mean age was 2.9 years (range, 0.1 to 13.9 years). CrC was less than 80 ml/minute per 1.73 m2 in 14 children, and Schwartz was less than 80 ml/minute per 1.73 m2 in 9 children. Correlations between inverse of B2M and CrC (r = 0.477) and between inverse of B2M and Schwartz (r = 0.697) were better than correlations between inverse of cystatin C and CrC (r = 0.390) or Schwartz (r = 0.586) and better than correlations between inverse of creatinine and CrC (r = 0.104) or Schwartz (r = 0.442). The ability of serum cystatin C and B2M to identify a CrC rate and a Schwartz CrC rate under 80 ml/minute per 1.73 m2 was better than that of creatinine (areas under the ROC curve: 0.851 and 0.792 for cystatin C, 0.802 and 0.799 for B2M, and 0.633 and 0.625 for creatinine). Conclusion Serum cystatin C and B2M were confirmed as easy and useful markers, better than serum creatinine, to detect acute kidney injury in critically ill children. PMID:17519026

  3. Diverging Association of Reduced Glomerular Filtration Rate and Albuminuria With Coronary and Noncoronary Events in Patients With Type 2 Diabetes

    PubMed Central

    Solini, Anna; Penno, Giuseppe; Bonora, Enzo; Fondelli, Cecilia; Orsi, Emanuela; Arosio, Maura; Trevisan, Roberto; Vedovato, Monica; Cignarelli, Mauro; Andreozzi, Francesco; Nicolucci, Antonio; Pugliese, Giuseppe

    2012-01-01

    OBJECTIVE Although a reduced estimated glomerular filtration rate (eGFR) was shown to be a powerful independent predictor of cardiovascular disease (CVD), other studies suggested that it confers a much lower risk than albuminuria alone, whereas the combination of the two abnormalities is associated with multiplicative risk. This study aimed at assessing the independent association of previous CVD events, either total or by vascular bed, with eGFR and albuminuria and chronic kidney disease (CKD) phenotypes. RESEARCH DESIGN AND METHODS This cross-sectional study evaluated 15,773 patients with type 2 diabetes from the Renal Insufficiency And Cardiovascular Events (RIACE) Italian Multicenter Study in 19 outpatient diabetes clinics in years 2007–2008. Albuminuria was assessed by immunonephelometry or immunoturbidimetry. GFR was estimated by the simplified Modification of Diet in Renal Disease Study and the Chronic Kidney Disease-Epidemiology Collaboration equation. CKD was defined as an eGFR <60 mL/min/1.73 m2 or micro- or macroalbuminuria. Major acute CVD events were adjudicated based on hospital discharge records or specialist visits. RESULTS CVD risk increased linearly with eGFR decline and albuminuria and became significant for values <78 mL/min/1.73 m2 and ≥10.5 mg/24 h, respectively. Beyond traditional CVD risk factors, total CVD showed an independent association with albuminuria alone (odds ratio 1.20 [95% CI 1.08–1.33]), reduced eGFR alone (1.52 [1.34–1.73]), and both abnormalities (1.90 [1.66–2.19]). However, coronary events were associated predominantly with reduced eGFR alone, whereas cerebrovascular and peripheral events showed a stronger correlation with the albuminuric CKD phenotypes. CONCLUSIONS These data, although cross-sectional, show that reduced eGFR, irrespective of albuminuria, is associated with significant CVD, particularly in the coronary district. PMID:22124714

  4. Insulin increases glomerular filtration barrier permeability through PKGIα-dependent mobilization of BKCa channels in cultured rat podocytes.

    PubMed

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

    2015-08-01

    Podocytes are highly specialized cells that wrap around glomerular capillaries and comprise a key component of the glomerular filtration barrier. They are uniquely sensitive to insulin; like skeletal muscle and fat cells, they exhibit insulin-stimulated glucose uptake and express glucose transporters. Podocyte insulin signaling is mediated by protein kinase G type I (PKGI), and it leads to changes in glomerular permeability to albumin. Here, we investigated whether large-conductance Ca²⁺-activated K⁺ channels (BKCa) were involved in insulin-mediated, PKGIα-dependent filtration barrier permeability. Insulin-induced glomerular permeability was measured in glomeruli isolated from Wistar rats. Transepithelial albumin flux was measured in cultured rat podocyte monolayers. Expression of BKCa subunits was detected by RT-PCR. BKCa, PKGIα, and upstream protein expression were examined in podocytes with Western blotting and immunofluorescence. The BKCa-PKGIα interaction was assessed with co-immunoprecipitation. RT-PCR showed that primary cultured rat podocytes expressed mRNAs that encoded the pore-forming α subunit and four accessory β subunits of BKCa. The BKCa inhibitor, iberiotoxin (ibTX), abolished insulin-dependent glomerular albumin permeability and PKGI-dependent transepithelial albumin flux. Insulin-evoked albumin permeability across podocyte monolayers was also blocked with BKCa siRNA. Moreover, ibTX blocked insulin-induced disruption of the actin cytoskeleton and changes in the phosphorylation of PKG target proteins, MYPT1 and RhoA. These results indicated that insulin increased filtration barrier permeability through mobilization of BKCa channels via PKGI in cultured rat podocytes. This molecular mechanism may explain podocyte injury and proteinuria in diabetes. PMID:25952906

  5. Psychosocial stress and changes in estimated glomerular filtration rate among adults with diabetes mellitus

    PubMed Central

    Annor, Francis B.; Masyn, Katherine E.; Okosun, Ike S.; Roblin, Douglas W.; Goodman, Michael

    2015-01-01

    Background Psychosocial stress has been hypothesized to impact renal changes, but this hypothesis has not been adequately tested. The aim of this study was to examine the relationship between psychosocial stress and estimated glomerular filtration rate (eGFR) and to examine other predictors of eGFR changes among persons with diabetes mellitus (DM). Methods Data from a survey conducted in 2005 by a major health maintenance organization located in the southeastern part of the United States, linked to patients’ clinical and pharmacy records (n=575) from 2005 to 2008, was used. Study participants were working adults aged 25–59 years, diagnosed with DM but without advanced microvascular or macrovascular complications. eGFR was estimated using the Modification of Diet in Renal Disease equation. A latent psychosocial stress variable was created from five psychosocial stress subscales. Using a growth factor model in a structural equation framework, we estimated the association between psychosocial stress and eGFR while controlling for important covariates. Results The psychosocial stress variable was not directly associated with eGFR in the final model. Factors found to be associated with changes in eGFR were age, race, insulin use, and mean arterial pressure. Conclusion Among fairly healthy DM patients, we did not find any evidence of a direct association between psychosocial stress and eGFR changes after controlling for important covariates. Predictors of eGFR change in our population included age, race, insulin use, and mean arterial pressure. PMID:26484039

  6. Differential glomerular filtration rate in diagnosis of renovascular hypertension and follow-up of balloon angioplasty

    SciTech Connect

    Lamki, L.; Spence, J.D.; MacDonald, A.C.; Roulston, M.

    1986-03-01

    Two hundred nine hypertensive patients with high stimulated plasma renin levels were screened for renovascular hypertension using Tc-99m DTPA renal scintigraphy. Differential glomerular filtration rate (Diff-GFR) was obtained by integrating the area under the background-subtracted renogram of each kidney between 1 and 3 minutes. 50 patients who also had undergone selective renal angiography were divided into four groups according to Diff-GFR contribution by one of the kidneys. If one kidney contributed 45-50% of total GFR, this was regarded as normal. A Diff-GFR of less than 45% was very considered to be very suggestive of renovascular hypertension in the appropriate clinical setting, while a Diff-GFR of less than 20% indicated that the renal artery might not be amenable to successful balloon angioplasty. Diff-GFR following balloon angioplasty closely reflected the early clinical response of the patients--and in some cases progressive Diff-GFR improvement was observed several months later. Diff-GFR as a scintigraphic criterion for renovascular hypertension has a sensitivity of 93%, specificity of 74%, and accuracy of 85%.

  7. Association of Glomerular Filtration Rate with Inflammation in Polycystic Ovary Syndrome

    PubMed Central

    Gozukara, Ilay Ozturk; Gozukara, Kerem Han; Kucur, Suna Kabil; Karakılıc, Eda Ulku; Keskin, Havva; Akdeniz, Derya; Aksoy, Ayse Nur; Carlıoglu, Ayse

    2015-01-01

    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 Endocrinol- ogy 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 val- ues than control patients, the renal function was within normal limits. Increased GFR in PCOS women positively correlates with elevated serum CRP and uric acid. PMID:26246875

  8. Measurement of single-kidney glomerular filtration function from magnetic resonance perfusion renography.

    PubMed

    Zeng, Meiying; Cheng, Yingsheng; Zhao, Binghui

    2015-08-01

    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. PMID:26032130

  9. Technical note: Use of a simplified equation for estimating glomerular filtration rate in beef cattle.

    PubMed

    Murayama, I; Miyano, A; Sasaki, Y; Hirata, T; Ichijo, T; Satoh, H; Sato, S; Furuhama, K

    2013-11-01

    This study was performed to clarify whether a formula (Holstein equation) based on a single blood sample and the isotonic, nonionic, iodine contrast medium iodixanol in Holstein dairy cows can apply to the estimation of glomerular filtration rate (GFR) for beef cattle. To verify the application of iodixanol in beef cattle, instead of the standard tracer inulin, both agents were coadministered as a bolus intravenous injection to identical animals at doses of 10 mg of I/kg of BW and 30 mg/kg. Blood was collected 30, 60, 90, and 120 min after the injection, and the GFR was determined by the conventional multisample strategies. The GFR values from iodixanol were well consistent with those from inulin, and no effects of BW, age, or parity on GFR estimates were noted. However, the GFR in cattle weighing less than 300 kg, aged<1 yr old, largely fluctuated, presumably due to the rapid ruminal growth and dynamic changes in renal function at young adult ages. Using clinically healthy cattle and those with renal failure, the GFR values estimated from the Holstein equation were in good agreement with those by the multisample method using iodixanol (r=0.89, P=0.01). The results indicate that the simplified Holstein equation using iodixanol can be used for estimating the GFR of beef cattle in the same dose regimen as Holstein dairy cows, and provides a practical and ethical alternative. PMID:24045472

  10. Glomerular filtration rate and urine osmolality in unilateral ureteropelvic junction obstruction

    PubMed Central

    Gheissari, Alaleh; Nematbakhsh, Mehdi; Amir-Shahkarami, Seyed Mohammad; Alizadeh, Farshid; Merrikhi, Alireza

    2013-01-01

    Background: Renal maldevelopment, interstitial fibrosis, ischemic atrophy, decreased glomerular filtration rate (GFR), and renal blood flow (RBF) are inevitable consequences of chronic kidney obstruction that only partially improve after early intervention. There are only few studies that evaluated urine osmolality in affected kidney and its correlation with short-term outcome. Materials and Methods: Thirty patients (age<1 year) with unilateral ureteropelvic junction obstruction (UUPJO) were enrolled in this study. UUPJO was confirmed using Technetium 99 isotope scans and the patients were indicated to be operated afterward. Urine and blood samples were obtained before, 24, 48, and 72 h after the surgery. The serum level of blood urea nitrogen, creatinine, and glucose were measured. GFR, urine osmolality (measured and calculated), and urine specific gravity were determined too. Results: Cortical thickness of hydronephrotic kidney was significantly increased 6 months after the surgery. GFR was significantly increased 72-h postsurgery compared to before operation. Neither means of calculated nor of measured urine osmolalities were significantly different in various stages. The last calculated urine osmolality (72 h) had significant correlation with the last measured osmolality (72 h); r=0.962, P=0.0001. The last GFR (72 h) had positive significant correlation with GFR before the surgery and GFRs at 24 and 48 h postsurgery. Using regression tests, only the before surgery GFR was the predictor of the last GFR(72 h). Conclusion: In UUPJO the measured and calculated urine osmolality of the affected kidney did not differ. In addition, GFR before surgery should be considered as the predictor of the GFR shortly after repair. PMID:24520546

  11. Water-Soluble Vitamins in People with Low Glomerular Filtration Rate or On Dialysis: A Review

    PubMed Central

    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. PMID:23859229

  12. Determination of glomerular filtration rate with 99mTc-DTPA in clinical practice.

    PubMed

    Galli, G; Rufini, V; Meduri, G; Piraccini, R; D'Andrea, G

    1994-12-01

    In order to assess the practical reliability of glomerular filtration rate (GFR) determination with 99mTc-DTPA and plasma sampling, the authors compared the results obtained with 51Cr-EDTA and 99mTc-DTPA in 50 patients using five easily applied methods (two double-plasma-sample methods and three single-plasma-sample methods), and two kits with different compositions. It was observed that: 1) there is no difference between the results obtained with the two different kits. 2) Compared with 51Cr-EDTA the 99mTc-DTPA overestimates the result by about 2 mL/min: precision is slightly lower with 99mTc-DTPA than with 51Cr-EDTA but is sufficient for practical use. 3) The method recommended by the authors on the basis of this experience is the Russell's method with two samples. 4) The simplified methods with one sample give comparable results to the Russell's method for GFR levels between 50 and 115 mL/min, while the results are unsatisfactory below 50 mL/min. 5) Among the single-sample methods, the authors suggest that of Christensen and Groth. 6) A preliminary estimate of GFR (from the serum creatinine level, for instance) is useful for the choice between double-plasma-sample methods and simplified methods. In conclusion, the authors consider that the estimation of GFR with 99mTc-DTPA can be performed efficiently in clinical practice even when operating in absolutely routine conditions. PMID:7786917

  13. Glomerular filtration rate in patients with atrial fibrillation and 1-year outcomes

    PubMed Central

    Boriani, Giuseppe; Laroche, Cécile; Diemberger, Igor; Popescu, Mircea Ioachim; Rasmussen, Lars Hvilsted; Petrescu, Lucian; Crijns, Harry J. G. M.; Tavazzi, Luigi; Maggioni, Aldo P.; Lip, Gregory Y. H.

    2016-01-01

    We assessed 1-year outcomes in patients with atrial fibrillation enrolled in the EurObservational Research Programme AF General Pilot Registry (EORP-AF), in relation to kidney function, as assessed by glomerular filtration rate (eGFR). In a cohort of 2398 patients (median age 69 years; 61% male), eGFR (ml/min/1.73 m2) calculated using the CKD-EPI formula was ≥80 in 35.1%, 50–79 in 47.2%, 30–49 in 13.9% and <30 in 3.7% of patients. In a logistic regression analysis, eGFR category was an independent predictor of stroke/TIA or death, with elevated odds ratios associated with severe to mild renal impairment, ie. eGFR < 30 ml/min/1.73 m2 [OR 3.641, 95% CI 1.572–8.433, p < 0.0001], 30–49 ml/min/1.73 m2 [OR 3.303, 95% CI 1.740–6.270, p = 0.0026] or 50–79 ml/min/1.73 m2 [OR 2.094, 95% CI 1.194–3.672, p = 0.0003]. The discriminant capability for the risk of death was tested among various eGFR calculation algorithms: the best was the Cockcroft-Gault equation adjusted for BSA, followed by Cockcroft-Gault equation, and CKD-EPI equation, while the worst was the MDRD equation. In conclusion in this prospective observational registry, renal function was a major determinant of adverse outcomes at 1 year, and even mild or moderate renal impairments were associated with an increased risk of stroke/TIA/death. PMID:27466080

  14. The control of glomerular filtration rate and renal blood flow in chronically volume-expanded rats.

    PubMed Central

    Davis, J M; Häberle, D A; Kawata, T

    1988-01-01

    1. Chronic volume expansion by dietary salt loading practically abolishes tubuloglomerular feed-back (TGF) by means of a humoral inhibitor in tubular fluid. Elimination of the vasoconstrictor influence of feed-back does not, however, increase glomerular filtration rate (GFR) and renal blood flow (RBF), implying that chronic salt loading induces additional preglomerular vasoconstriction. This being so, the feed-back response which, although absent in free-flowing nephrons, can still be elicited by loop of Henle perfusion with Ringer solution, should be essentially normal, except that nephron GFR at any loop perfusion rate should be lower than in controls. Persistence of RBF, GFR and nephron GFR autoregulation would imply that autoregulation is achieved by a preglomerular resistance control system independent of feed-back. 2. These hypotheses were tested by clearance and micropuncture experiments in rats chronically fed a diet containing 40 g NaCl (kg food)-1. 3. RBF and GFR autoregulation indeed persisted, the former down to 90 mmHg compared with 105 mmHg in controls. In controls, nephron GFR measured distally was autoregulated down to 90 mmHg whereas that measured proximally was autoregulated only above 105 mmHg. In high-salt rats nephron GFR from both sites was autoregulated to 90 mmHg. 4. Loop of Henle perfusion with homologous tubular fluid in high-salt rats confirmed attenuation of feed-back. Loop perfusion with Ringer solution yielded a response comparable to that in controls (maximal reduction of nephron GFR to 57%, compared with 56% in controls). Absolute nephron GFR at any loop perfusion rate was lower in high-salt rats than in controls. 5. These observations confirm the initial hypotheses. Considering feed-back and autoregulation as independent, preglomerular resistance control mechanisms, together with elementary haemodynamic considerations, allows formulation of a renal haemodynamics model whose quantitative predictions regarding characteristics of RBF

  15. Association between Serum Bilirubin and Estimated Glomerular Filtration Rate among Diabetic Patients

    PubMed Central

    Katoh, Takeaki; Kawamoto, Ryuichi; Kohara, Katsuhiko; Miki, Tetsuro

    2015-01-01

    The subjects comprised 230 men aged 77 ± 10 (range: 50–100) years and 279 women aged 81 ± 10 (50–101) years that visited the medical department. We examined the relationship between increased serum bilirubin and renal function evaluated by estimated glomerular filtration rate (eGFR) using CKD-EPI equations modified by a Japanese coefficient. Compared with the fourth quartile in serum bilirubin (1.01–1.97 mg/dL), the nonadjusted, age and gender-adjusted, and multivariate-adjusted odds ratios {95% confidence interval (CI)} of eGFR <60 mL/min/1.73 m2 for the first quartile in serum bilirubin (0.13–0.50 mg/dL) were 2.08 (1.25–3.44), 1.82 (1.07–3.09), and 1.53 (0.83–2.81), respectively. Moreover, compared with the fourth quartile, nonadjusted, age and gender-adjusted, and multivariate-adjusted odds ratios (95% CI) of eGFR <45 mL/min/1.73 m2 for the first quartile were 3.50 (1.95–6.23), 3.12 (1.72–5.65), and 3.53 (1.71–7.26), respectively. The data were further stratified by gender, age, medication (antihypertensive, antidyslipidemic, and antidiabetic agents), and prevalence of cardiovascular disease (CVD). The standardized coefficients for eGFR were significant in all the subgroups other than the prevalence of CVD, and there were significant interactions between the two groups regarding CVD. Our data demonstrated an independent positive association between serum bilirubin and eGFR among diabetic patients.

  16. Renal Handling of Sclerostin in Response to Acute Glomerular Filtration Decline.

    PubMed

    Kakareko, K; Rydzewska-Rosolowska, A; Brzosko, S; Gozdzikiewicz-Lapinska, J; Koc-Zorawska, E; Samocik, P; Kozlowski, R; Mysliwiec, M; Naumnik, B; Hryszko, T

    2016-07-01

    Deterioration of glomerular filtration rate (GFR) is associated with alterations of bone metabolism. It translates clinically to bone fragility and increased fractures rate among patients with impaired GFR. Recently, sclerostin (SCL) gained much attention as an important factor in pathogenesis of mineral and bone disturbances in patients with renal diseases. There is no data about SCL behaviour in patients with acute GFR decline. The aim of this study was to evaluate the renal handling of SCL. This is a prospective, single-centre observational study in patients undergoing nephrectomy due to urological indications. Serum and urinary SCL levels were measured prior and after nephrectomy. 25 patients were enrolled. After surgery, eGFR significantly declined (from 87.4±19.7 to 67.7±25.7 ml/min/1.73 m(2), p<0.0001). Nephrectomy caused more than 20 times higher renal fractional excretion of SCL [0.15 (interquartile range, IQR 0.09-0.40) vs. 2.78 (IQR 1.51-4.02)%, p<0.001], while its serum level remained intact [0.69 (IQR 0.57-0.90 vs. 0.65 (IQR 0.53-0.88) ng/ml, p=0.4]. The magnitude of eGFR reduction was associated inversely with change in urinary SCL fractional excretion (r=-0.6, p=0.001) and with alteration in serum SCL level (r=-0.5, p=0.01). Our results suggest that increased serum SCL concentrations at moderately reduced GFR are not due to diminished renal clearance. At more severely decreased GFR, elevated SCL concentration results from both increased production and reduced renal elimination. PMID:27214309

  17. Glomerular filtration rate in patients with atrial fibrillation and 1-year outcomes.

    PubMed

    Boriani, Giuseppe; Laroche, Cécile; Diemberger, Igor; Popescu, Mircea Ioachim; Rasmussen, Lars Hvilsted; Petrescu, Lucian; Crijns, Harry J G M; Tavazzi, Luigi; Maggioni, Aldo P; Lip, Gregory Y H

    2016-01-01

    We assessed 1-year outcomes in patients with atrial fibrillation enrolled in the EurObservational Research Programme AF General Pilot Registry (EORP-AF), in relation to kidney function, as assessed by glomerular filtration rate (eGFR). In a cohort of 2398 patients (median age 69 years; 61% male), eGFR (ml/min/1.73 m(2)) calculated using the CKD-EPI formula was ≥80 in 35.1%, 50-79 in 47.2%, 30-49 in 13.9% and <30 in 3.7% of patients. In a logistic regression analysis, eGFR category was an independent predictor of stroke/TIA or death, with elevated odds ratios associated with severe to mild renal impairment, ie. eGFR < 30 ml/min/1.73 m(2) [OR 3.641, 95% CI 1.572-8.433, p < 0.0001], 30-49 ml/min/1.73 m(2) [OR 3.303, 95% CI 1.740-6.270, p = 0.0026] or 50-79 ml/min/1.73 m2 [OR 2.094, 95% CI 1.194-3.672, p = 0.0003]. The discriminant capability for the risk of death was tested among various eGFR calculation algorithms: the best was the Cockcroft-Gault equation adjusted for BSA, followed by Cockcroft-Gault equation, and CKD-EPI equation, while the worst was the MDRD equation. In conclusion in this prospective observational registry, renal function was a major determinant of adverse outcomes at 1 year, and even mild or moderate renal impairments were associated with an increased risk of stroke/TIA/death. PMID:27466080

  18. Chronic kidney disease and automatic reporting of estimated glomerular filtration rate: new developments and revised recommendations.

    PubMed

    Johnson, David W; Jones, Graham R D; Mathew, Timothy H; Ludlow, Marie J; Doogue, Matthew P; Jose, Matthew D; Langham, Robyn G; Lawton, Paul D; McTaggart, Steven J; Peake, Michael J; Polkinghorne, Kevan; Usherwood, Tim

    2012-08-20

    The publication of the Australasian Creatinine Consensus Working Group's position statements in 2005 and 2007 resulted in automatic reporting of estimated glomerular filtration rate (eGFR) with requests for serum creatinine concentration in adults, facilitated the unification of units of measurement for creatinine and eGFR, and promoted the standardisation of assays. New advancements and continuing debate led the Australasian Creatinine Consensus Working Group to reconvene in 2010. The working group recommends that the method of calculating eGFR should be changed to the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula, and that all laboratories should report eGFR values as a precise figure to at least 90 mL/min/1.73 m(2). Age-related decision points for eGFR in adults are not recommended, as although an eGFR < 60 mL/min/1.73 m(2) is very common in older people, it is nevertheless predictive of significantly increased risks of adverse clinical outcomes, and should not be considered a normal part of ageing.If using eGFR for drug dosing, body size should be considered, in addition to referring to the approved product information. For drugs with a narrow therapeutic index, therapeutic drug monitoring or a valid marker of drug effect should be used to individualise dosing. The CKD-EPI formula has been validated as a tool to estimate GFR in some populations of non-European ancestry living in Western countries. Pending publication of validation studies, the working group also recommends that Australasian laboratories continue to automatically report eGFR in Aboriginal and Torres Strait Islander peoples. The working group concluded that routine calculation of eGFR is not recommended in children and youth, or in pregnant women. Serum creatinine concentration (preferably using an enzymatic assay for paediatric patients) should remain as the standard test for kidney function in these populations. PMID:22900871

  19. Estimation of Glomerular Filtration Rate Based on Serum Cystatin C versus Creatinine in a Uruguayan Population

    PubMed Central

    Lujambio, Inés; Sottolano, Mariana; Robaina, Sebastián; Carusso, Florencia; da Rosa, Alicia; Ríos, Ana Carina; Olascoaga, Alicia; Gadola, Liliana; Noboa, Oscar; Staessen, Jan A.; Boggia, José

    2014-01-01

    Background. Estimation of glomerular filtration rate (eGFR) from biomarkers has evolved and multiple equations are available to estimate renal function at bedside. Methods. In a random sample of 119 Uruguayans (54.5% women; 56.2 years (mean)), we used Bland and Altman's method and Cohen's kappa statistic to assess concordance on a continuous or categorical (eGFR < 60 versus ≥60 mL/min/1.73 m2) scale between eGFRcys (reference) and eGFR derived from serum creatinine according to the Modification of Diet in Renal Disease (eGFRmdrd) or the Chronic Kidney Disease Epidemiology Collaboration equations (eGFRepi) or from both serum cystatin C and creatinine (eGFRmix). Results. In all participants, eGFRmdrd, eGFRepi, and eGFRmix were, respectively, 9.7, 11.5, and 5.6 mL/min/1.73 m2 higher (P < 0.0001) than eGFRcys. The prevalence of eGFR <60 mL/min/1.73 m2 was the highest for eGFRcys (21.8%), intermediate for eGFRmix (11.8%), and the lowest for eGFRmdrd (5.9%) and eGFRepi (3.4%). Using eGFRcys as reference, we found only fair agreement with the equations based on creatinine (Cohen's kappa statistic 0.15 to 0.23). Conclusion. Using different equations we reached clinically significant differences in the estimation of renal function. eGFRcys provides lower estimates, resulting in higher prevalence of eGFR <60 mL/min/1.73 m2. PMID:25215234

  20. Effect of prenatal programming and postnatal rearing on glomerular filtration rate in adult rats

    PubMed Central

    Lozano, German; Elmaghrabi, Ayah; Salley, Jordan; Siddique, Khurrum; Gattineni, Jyothsna

    2014-01-01

    The present study examined whether a prenatal low-protein diet programs a decrease in glomerular filtration rate (GFR) and an increase in systolic blood pressure (BP). In addition, we examined whether altering the postnatal nutritional environment of nursing neonatal rats affected GFR and BP when rats were studied as adults. Pregnant rats were fed a normal (20%) protein diet or a low-protein diet (6%) during the last half of pregnancy until birth, when rats were fed a 20% protein diet. Mature adult rats from the prenatal low-protein group had systolic hypertension and a GFR of 0.38 ± 0.03 versus 0.57 ± 0.05 ml·min−1·100 g body wt−1 in the 20% group (P < 0.01). In cross-fostering experiments, mothers continued on the same prenatal diet until weaning. Prenatal 6% protein rats cross-fostered to a 20% mother on day 1 of life had a GFR of 0.53 ± 0.05 ml·min−1·100 g body wt−1, which was not different than the 20% group cross-fostered to a different 20% mother (0.45 ± 0.04 ml·min−1·100 g body wt−1). BP in the 6% to 20% group was comparable with the 20% to 20% group. Offspring of rats fed either 20% or 6% protein diets during pregnancy and cross-fostered to a 6% mother had elevated BP but a comparable GFR normalized to body weight as the 20% to 20% control group. Thus, a prenatal low-protein diet causes hypertension and a reduction in GFR in mature adult offspring, which can be modified by postnatal rearing. PMID:25537745

  1. Analgesia dose prescribing and estimated glomerular filtration rate decline: a general practice database linkage cohort study

    PubMed Central

    Nderitu, Paul; Doos, Lucy; Strauss, Vicky Y; Lambie, Mark; Davies, Simon J; Kadam, Umesh T

    2014-01-01

    Objective We aimed to quantify the short-term effect of non-steroidal anti-inflammatory drugs (NSAIDs), aspirin and paracetamol analgesia dose prescribing on estimated glomerular filtration rate (eGFR) decline in the general practice population. Design A population-based longitudinal clinical data linkage cohort study. Setting Two large general practices in North Staffordshire, UK. Participants Patients aged 40 years and over with ≥2 eGFR measurements spaced ≥90 days apart between 1 January 2009 and 31 December 2010 were selected. Exposure Using WHO Defined Daily Dose standardised cumulative analgesia prescribing, patients were categorised into non-user, normal and high-dose groups. Outcome measure The primary outcome was defined as a >5 mL/min/1.73 m2/year eGFR decrease between the first and last eGFR. Logistic regression analyses were used to estimate risk, adjusting for sociodemographics, comorbidity, baseline chronic kidney disease (CKD) status, renin-angiotensin-system inhibitors and other analgesia prescribing. Results There were 4145 patients (mean age 66 years, 55% female) with an analgesia prescribing prevalence of 17.2% for NSAIDs, 39% for aspirin and 22% for paracetamol and stage 3–5 CKD prevalence was 16.1% (n=667). Normal or high-dose NSAID and paracetamol prescribing was not significantly associated with eGFR decline. High-dose aspirin prescribing was associated with a reduced risk of eGFR decline in patients with a baseline (first) eGFR ≥60 mL/min/1.73 m2; OR=0.52 (95% CI 0.35 to 0.77). Conclusions NSAID, aspirin and paracetamol prescribing over 2 years did not significantly affect eGFR decline with a reduced risk of eGFR decline in high-dose aspirin users with well-preserved renal function. However, the long-term effects of analgesia use on eGFR decline remain to be determined. PMID:25138808

  2. Determination of Single-Kidney Glomerular Filtration Rate in Human Subjects by Using CT

    PubMed Central

    Kwon, Soon Hyo; Saad, Ahmed; Herrmann, Sandra M.; Textor, Stephen C.

    2015-01-01

    Purpose To test the hypothesis that computed tomography (CT)–derived measurements of single-kidney glomerular filtration rate (GFR) obtained in human subjects with 64-section CT agree with those obtained with iothalamate clearance, a rigorous reference standard. Materials and Methods The institutional review board approved this HIPAA-compliant study, and written informed consent was obtained. Ninety-six patients (age range, 51–73 years; 46 men, 50 women) with essential (n = 56) or renovascular (n = 40) hypertension were prospectively studied in controlled conditions (involving sodium intake and renin-angiotensin blockade). Single-kidney perfusion, volume, and GFR were measured by using multidetector CT time-attenuation curves and were compared with GFR measured by using iothalamate clearance, as assigned to the right and left kidney according to relative volumes. The reproducibility of CT GFR over a 3-month period (n = 21) was assessed in patients with renal artery stenosis who were undergoing stable medical treatment. Statistical analysis included the t test, Wilcoxon signed rank test, linear regression, and Bland-Altman analysis. Results CT GFR values were similar to those of iothalamate clearance (mean ± standard deviation, 38.2 mL/min ± 18 vs 41.6 mL/min ± 17; P = .062). Stenotic kidney CT GFR in patients with renal artery stenosis was lower than contralateral kidney GFR or essential hypertension single-kidney GFR (mean, 23.1 mL/min ± 13 vs 36.9 mL/min ± 17 [P = .0008] and 45.2 mL/min ± 16 [P = .019], respectively), as was iothalamate clearance (mean, 26.9 mL/min ± 14 vs 38.5 mL/min ± 15 [P = .0004] and 49.0 mL/min ± 14 [P = .001], respectively). CT GFR correlated well with iothalamate GFR (linear regression, CT GFR = 0.88*iothalamate GFR, r2 = 0.89, P < .0001), and Bland-Altman analysis was used to confirm the agreement. CT GFR was also moderately reproducible in medically treated patients with renal artery stenosis (concordance coefficient

  3. Estimated Glomerular Filtration Rate and Mortality among Patients with Coronary Heart Disease

    PubMed Central

    Ding, Ding; Xia, Min; Li, Dan; Yang, Yunou; Li, Qing; Liu, Jiaxing; Chen, Xuechen; Hu, Gang; Ling, Wenhua

    2016-01-01

    Objective The association between estimated glomerular filtration rate (eGFR) and the risk of mortality among patients with coronary heart disease (CHD) is complex and still unclear. The aim of this study was to evaluate the effect of eGFR on the risk prediction of all-cause and cardiovascular disease (CVD) mortality with a long follow-up period among patients with CHD in China. Methods We conducted a prospective cohort study of 3276 Chinese patients with CHD. Cox proportional hazards regression models were used to estimate the association of different levels of eGFR with the risks of mortality. Results During a mean follow-up period of 4.9 years, 293 deaths were identified. The multivariable-adjusted hazard ratios associated with different levels of eGFR (≥90 [reference group], 60–89, 30–59, 15–29 ml/min per 1.73m2) at baseline were 1.00, 1.28 (95% confidence interval [CI], 0.87–1.88), 1.96 (95% CI, 1.31–2.94), and 3.91 (95% CI, 2.15–7.13) (P <0.001) for all-cause mortality, and 1.00, 1.26 (95% CI, 0.78–2.04), 1.94 (95% CI, 1.17–3.20), and 3.77 (95% CI, 1.80–7.89) (P <0.001) for CVD mortality, respectively. After excluding subjects who died during the first 2 years of follow-up (n = 113), the graded associations of eGFR with the risks of all-cause and CVD morality were still present. The addition of eGFR to a model including traditional cardiovascular risk factors resulted in significant improvement in the prediction of all-cause and CVD mortality. Conclusions Reduced eGFR (< 60 ml/min per 1.73 m2) at baseline is associated with increased risks of all-cause and CVD mortality among Chinese patients with CHD. PMID:27537335

  4. Incomplete Reversibility of Estimated Glomerular Filtration Rate Decline Following Tenofovir Disoproxil Fumarate Exposure

    PubMed Central

    Jose, Sophie; Hamzah, Lisa; Campbell, Lucy J.; Hill, Teresa; Fisher, Martin; Leen, Clifford; Gilson, Richard; Walsh, John; Nelson, Mark; Hay, Phillip; Johnson, Margaret; Chadwick, David; Nitsch, Dorothea; Jones, Rachael; Sabin, Caroline A.; Post, Frank A.; Ainsworth, Jonathan; Anderson, Jane; Babiker, Abdel; Chadwick, David; Delpech, Valerie; Dunn, David; Fisher, Martin; Gazzard, Brian; Gilson, Richard; Gompels, Mark; Hay, Phillip; Hill, Teresa; Johnson, Margaret; Kegg, Stephen; Leen, Clifford; Nelson, Mark; Orkin, Chloe; Palfreeman, Adrian; Phillips, Andrew; Pillay, Deenan; Post, Frank; Sabin, Caroline; Sachikonye, Memory; Schwenk, Achim; Walsh, John; Hill, Teresa; Huntington, Susie; Josie, Sophie; Phillips, Andrew; Sabin, Caroline; Thornton, Alicia; Dunn, David; Glabay, Adam; Orkin, C.; Garrett, N.; Lynch, J.; Hand, J.; de Souza, C.; Fisher, M.; Perry, N.; Tilbury, S.; Churchill, D.; Gazzard, B.; Nelson, M.; Waxman, M.; Asboe, D.; Mandalia, S.; Delpech, V.; Anderson, J.; Munshi, S.; Korat, H.; Poulton, M.; Taylor, C.; Gleisner, Z.; Campbell, L.; Babiker, Abdel; Dunn, David; Glabay, Adam; Gilson, R.; Brima, N.; Williams, I.; Schwenk, A.; Ainsworth, J.; Wood, C.; Miller, S.; Johnson, M.; Youle, M.; Lampe, F.; Smith, C.; Grabowska, H.; Chaloner, C.; Puradiredja, D.; Walsh, J.; Weber, J.; Ramzan, F.; Mackie, N.; Winston, A.; Leen, C.; Wilson, A.; Gompels, M.; Allan, S.; Palfreeman, A.; Moore, A.; Chadwick, D.; Wakeman, K.; Kegg, Stephen; Main, Paul; Mitchell; Hunter; Sachikonye, Memory; Hay, Phillip; Dhillon, Mandip

    2014-01-01

    Background. Tenofovir disoproxil fumarate (TDF) has been linked to renal impairment, but the extent to which this impairment is reversible is unclear. We aimed to investigate the reversibility of renal decline during TDF therapy. Methods. Cox proportional hazards models assessed factors associated with discontinuing TDF in those with an exposure duration of >6 months. In those who discontinued TDF therapy, linear piecewise regression models estimated glomerular filtration rate (eGFR) slopes before initiation of, during, and after discontinuation of TDF therapy. Factors associated with not achieving eGFR recovery 6 months after discontinuing TDF were assessed using multivariable logistic regression. Results. We observed declines in the eGFR during TDF exposure (mean slopes, −15.7 mL/minute/1.73 m2/year [95% confidence interval {CI}, −20.5 to −10.9] during the first 3 months and −3.1 mL/minute/1.73 m2/year [95% CI, −4.6 to −1.7] thereafter) and evidence of eGFR increases following discontinuation of TDF therapy (mean slopes, 12.5 mL/minute/1.73 m2/year [95% CI, 8.9–16.1] during the first 3 months and 0.8 mL/minute/1.73 m2/year [95% CI, .1–1.5] thereafter). Following TDF discontinuation, 38.6% of patients with a decline in the eGFR did not experience recovery. A higher eGFR at baseline, a lower eGFR after discontinuation of TDF therapy, and more-prolonged exposure to TDF were associated with an increased risk of incomplete recovery 6 months after discontinuation of TDF therapy. Conclusions. This study shows that a decline in the eGFR during TDF therapy was not fully reversible in one third of patients and suggests that prolonged TDF exposure at a low eGFR should be avoided. PMID:24585896

  5. Clinical practice guidelines for chronic kidney disease in adults: Part II. Glomerular filtration rate, proteinuria, and other markers.

    PubMed

    Johnson, Cynda Ann; Levey, Andrew S; Coresh, Josef; Levin, Adeera; Lau, Joseph; Eknoyan, Garabed

    2004-09-15

    The Kidney Disease Outcome Quality Initiative of the National Kidney Foundation published clinical practice guidelines on chronic kidney disease in February 2002. Of the 15 guidelines, the first six are of greatest relevance to family physicians. Part II of this two-part review covers guidelines 4, 5, and 6. Glomerular filtration rate is the best overall indicator of kidney function. It is superior to the serum creatinine level, which varies with age, sex, and race and often does not reflect kidney function accurately. The glomerular filtration rate can be estimated using prediction equations that take into account the serum creatinine level and some or all of specific variables (age, sex, race, body size). In many patients, estimates of the glomerular filtration rate can replace 24-hour urine collections for creatinine clearance measurements. Urine dipsticks generally are acceptable for detecting proteinuria. To quantify proteinuria, the ratio of protein or albumin to creatinine in an untimed (spot) urine sample is an accurate alternative to measurement of protein excretion in a 24-hour urine collection. Patients with persistent proteinuria have chronic kidney disease. Other techniques for evaluating patients with chronic kidney disease include examination of urinary sediment, urine dipstick testing for red and white blood cells, and imaging studies of the kidneys (especially ultrasonography). These techniques also can help determine the underlying cause of chronic kidney disease. Family physicians should weigh the value of the National Kidney Foundation guidelines for their clinical practice based on the strength of evidence and perceived cost-effectiveness until additional evidence becomes available on the usefulness of the recommended quality indicators. PMID:15456118

  6. Verification on the use of the Inoue method for precisely determining glomerular filtration rate in Philippine pediatrics

    NASA Astrophysics Data System (ADS)

    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.

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

    PubMed

    Stæhr, Mette; Buhl, Kristian B; Andersen, René F; Svenningsen, Per; Nielsen, Flemming; Hinrichs, Gitte Rye; Bistrup, Claus; Jensen, Boye L

    2015-08-01

    In nephrotic syndrome, aberrant glomerular filtration of plasminogen and conversion to active plasmin in preurine are thought to activate proteolytically epithelial sodium channel (ENaC) and contribute to sodium retention and edema. The ENaC blocker amiloride is an off-target inhibitor of urokinase-type plasminogen activator (uPA) in vitro. It was hypothesized that uPA is abnormally filtered to preurine and is inhibited in urine by amiloride in nephrotic syndrome. This was tested by determination of Na(+) balance, uPA protein and activity, and amiloride concentration in urine from rats with puromycin aminonucleoside (PAN)-induced nephrotic syndrome. Urine samples from 6 adult and 18 pediatric patients with nephrotic syndrome were analyzed for uPA activity and protein. PAN treatment induced significant proteinuria in rats which coincided with increased urine uPA protein and activity, increased urine protease activity, and total plasminogen/plasmin concentration and Na(+) retention. Amiloride (2 mg·kg(-1)·24 h(-1)) concentration in urine was in the range 10-20 μmol/l and reduced significantly urine uPA activity, plasminogen activation, protease activity, and sodium retention in PAN rats, while proteinuria was not altered. In paired urine samples, uPA protein was significantly elevated in urine from children with active nephrotic syndrome compared with remission phase. In six adult nephrotic patients, urine uPA protein and activity correlated positively with 24 h urine protein excretion. In conclusion, nephrotic syndrome is associated 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. PMID:25972510

  8. Relationship of glomerular filtration rate based on serum iodixanol clearance to IRIS staging in cats with chronic kidney disease.

    PubMed

    Iwama, Ryosuke; Sato, Tsubasa; Katayama, Masaaki; Shimamura, Shunsuke; Satoh, Hiroshi; Ichijo, Toshihiro; Furuhama, Kazuhisa

    2015-08-01

    We examined the correlation between the glomerular filtration rate (GFR) estimated from an equation based on the serum iodixanol clearance technique and International Renal Interest Society (IRIS) stages of chronic kidney disease (CKD) in cats. The equation included the injection dose, sampling time, serum concentration and estimated volume of distribution (Vd) of the isotonic, nonionic, contrast medium iodixanol as a test tracer. The percent changes in the median basal GFR values calculated from the equation in CKD cats resembled those of IRIS stages 1-3. These data validate the association between the GFR derived from the simplified equation and IRIS stages based on the serum creatinine concentration in cats with CKD. They describe the GFR ranges determined using single-sample iodixanol clearance for healthy cats and cats with various IRIS stages of CKD. PMID:25864431

  9. Validation of estimated renal function measurements compared with the isotopic glomerular filtration rate in an HIV-infected cohort.

    PubMed

    Bonjoch, Anna; Bayés, Beatriz; Riba, Joaquim; Puig, Jordi; Estany, Carla; Perez-Alvarez, Núria; Clotet, Bonaventura; Negredo, Eugènia

    2010-12-01

    We performed a cross-sectional study to determine the best method for estimating the glomerular filtration rate (GFR) in HIV-infected subjects. Isotopic GFR was correlated with 24-h urine creatinine clearance, cystatin C levels, and 3 creatinine-based equations-the Modification of Diet in Renal Disease (MDRD), Cockcroft-Gault (CG), and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)-in 15 patients. Cystatin C showed the strongest correlation with isotopic GFR (r=-0.760, p=0.001). When cystatin C was used as the reference variable for all 106 patients, CKD-EPI proved to be superior to the other equations (r=-0.671, p<0.001). Time with HIV infection, unsuppressed viral load, low CD4 T-cell counts, and use of protease inhibitors are related to an increased risk of renal impairment, leading us to recommend early initiation of antiretroviral therapy accompanied by a regular renal study. PMID:20887753

  10. Tumor necrosis factor-alpha-induced reduction of glomerular filtration rate in rats with fulminant hepatic failure.

    PubMed

    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. PMID:24887412

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

    PubMed

    Nielsen, Stine E; Andersen, Steen; Zdunek, Dietmar; Hess, Georg; Parving, Hans-Henrik; Rossing, Peter

    2011-05-01

    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 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 albumin excretion 1141 mg/24 h. Patients with the highest compared with the lowest quartile of urinary NGAL at baseline had higher urinary KIM-1 levels and a significant decrease in their GFR each year. Using linear regression analysis, we found that elevated urinary NGAL and KIM-1 concentrations were associated with a faster decline in GFR, but not after adjustment for known promoters of progression. Urinary LFABP was not related to decline in GFR. Losartan treatment (100 mg/day) reduced urinary KIM-1 by 43% over a 12-month period. Thus, urine biomarker measurements in patients with type 1 diabetic nephropathy did not provide additional prognostic information to that of known progression promoters. PMID:21270761

  12. The association between glomerular filtration rate and left ventricular function in two independent community-based cohorts of elderly

    PubMed Central

    Nerpin, Elisabet; Ingelsson, Erik; Risérus, Ulf; Sundström, Johan; Andren, Bertil; Jobs, Elisabeth; Larsson, Anders; Lars, Lind; Ärnlöv, Johan

    2014-01-01

    Background The cardiorenal syndrome, the detrimental bi-directional interplay between symptomatic heart failure and chronic kidney disease, is a major clinical challenge. Nonetheless, it is unknown if this interplay begins already at an asymptomatic stage. Therefore we investigated whether the glomerular filtration rate (GFR) is associated with left ventricular function in participants free from clinical heart failure and with a left ventricular ejection fraction (LVEF) >40% and with pre-specified sub-group analyses in individuals with a GFR >60 mL/min/m2. Methods Two independent community-based cohorts were used; the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS; n = 911; 50% women; mean age: 70 years) and the Uppsala Longitudinal Study of Adult Men (ULSAM; n = 538; mean age: 71 years). We investigated cross-sectional association between cystatin C-based GFR (estimated glomerular function [eGFR]) and systolic (LVEF), diastolic- (isovolumic relaxation time [IVRT]) and global left ventricular function (myocardial performance index [MPI]) determined by echocardiography. Results In both PIVUS and ULSAM, higher eGFR was significantly associated with higher LVEF (P = 0.004 [PIVUS] and P = 0.005 [ULSAM]). In PIVUS, higher eGFR was significantly associated with lower IVRT (P = 0.001) and MPI (P = 0.006), in age- and sex-adjusted models. After further adjustment for cardiovascular risk factors, the association between higher eGFR and higher LVEF was still statistically significant (P = 0.008 [PIVUS] and P = 0.02 [ULSAM]). In PIVUS, the age- and sex-adjusted association between eGFR and left ventricular function was similar in participants with eGFR >60 mL/min/m2. Conclusions Our data suggest that the interplay between kidney and heart function begins prior to the development of symptomatic heart failure and kidney disease. PMID:24916339

  13. A Comprehensive Software and Database Management System for Glomerular Filtration Rate Estimation by Radionuclide Plasma Sampling and Serum Creatinine Methods

    PubMed Central

    Jha, Ashish Kumar

    2015-01-01

    Glomerular filtration rate (GFR) estimation by plasma sampling method is considered as the gold standard. However, this method is not widely used because the complex technique and cumbersome calculations coupled with the lack of availability of user-friendly software. The routinely used Serum Creatinine method (SrCrM) of GFR estimation also requires the use of online calculators which cannot be used without internet access. We have developed user-friendly software “GFR estimation software” which gives the options to estimate GFR by plasma sampling method as well as SrCrM. We have used Microsoft Windows® as operating system and Visual Basic 6.0 as the front end and Microsoft Access® as database tool to develop this software. We have used Russell's formula for GFR calculation by plasma sampling method. GFR calculations using serum creatinine have been done using MIRD, Cockcroft-Gault method, Schwartz method, and Counahan-Barratt methods. The developed software is performing mathematical calculations correctly and is user-friendly. This software also enables storage and easy retrieval of the raw data, patient's information and calculated GFR for further processing and comparison. This is user-friendly software to calculate the GFR by various plasma sampling method and blood parameter. This software is also a good system for storing the raw and processed data for future analysis. PMID:26097422

  14. High performance liquid chromatographic measurement of iothalamate in human serum and urine for evaluation of glomerular filtration rate.

    PubMed

    Bi, Daoqin; Leary, Kevin J; Weitz, Julie A; Cherstniakova, Svetlana A; Reil, Michael A; Roy, Michael J; Cantilena, Louis R

    2007-09-01

    A simple and sensitive HPLC-UV assay was developed for the measurement of iothalamate (IOT) in human serum and urine. Chromatographic separation was achieved using an embedded-carbamate-group bonded RP18 column and mobile phase consisting of 50 mM monobasic sodium phosphate and methanol (90:10, v/v) without the addition of ion-pair reagents. The assay demonstrated a high analytical reliability within the IOT concentration range of 1-150 microg/ml in serum and 25-1500 microg/ml in urine. The relative standard deviations (RSDs) for intra- and inter-day analysis were less than 5.1% in all cases. This method has been used for the evaluation of glomerular filtration rate (GFR) in subjects participating in a phase I clinical trial of a novel antimalarial medicine. The average baseline GFR was 100.41+/-19.99 ml/min/1.73 m(2) in 119 healthy volunteers. The assay may also allow the simultaneous measurements of p-aminohippuric acid (PAH), N-acetyl PAH (aPAH), and IOT with some modification. PAH, IOT, aPAH, and beta-hydroxyethyl-theophylline internal standard peaks appeared approximately at 2.5, 3.7, 5.9, and 11.8 min, respectively, in an isocratic run. PMID:17599846

  15. Estimated glomerular filtration rate, urine albumin excretion, and survival among patients consulting in public Chilean public primary care clinics.

    PubMed

    Rios, Alvaro; Lorca, Eduardo; Garmendia, María Luisa; Hirsch, Sandra; Sandoval, Verónica; Bunout, Daniel

    2016-04-01

    Chronic renal disease (CRD) in its pre-dialysis stage is an important risk factor for mortality among adults. The aim of this study was to assess the effects of CRD on mortality among consultants in Chilean public primary care clinics. We obtained information about serum creatinine, urinary albumin excretion (UAE), blood pressure, and body mass index of 5224 consultants [3379 females aged 67 (59-75) years and 1845 males aged 68 (59-75) years] in three clinics of Metropolitan Santiago. Kaplan-Meier curves and Cox proportional hazard regression models were used to determine risk factors for mortality, determined 41 months after obtaining the blood samples. During the follow-up period, 262 patients died (33% due to circulatory causes and 29% due to tumors). Kaplan-Meier curves showed that there was a significant association between survival, estimated glomerular filtration rate, and UAE. Cox models showed that serum creatinine, UAE, a lower body mass index, and a history of diabetes were significant mortality predictors. A sensitivity analysis performed eliminating extreme ages (less than 50 and more than 80 years), included high diastolic pressure as a predictor of survival. We conclude that among patients with CRD in its pre-dialysis stage, UAE is an important predictor of survival, along with serum creatinine. A low body mass index was associated with a higher mortality. PMID:26765359

  16. Coffee consumption and cystatin-C-based estimated glomerular filtration rates in healthy young adults: results of a clinical trial.

    PubMed

    Saito, Masafumi; Nemoto, Tohru; Tobimatsu, Satoshi; Ebata, Midori; Le, Yulan; Nakajima, Kei

    2011-01-01

    Recently it has been reported that the estimated glomerular filtration rate (eGFR) is higher in habitual coffee consumers than in noncoffee consumers. However, the causality remains unclear. Therefore, we conducted a clinical trial to investigate the effects of coffee consumption on kidney function. Nineteen asymptomatic nonsmokers aged 21-27 years old participated in this study. They consumed coffee (18 g coffee beans/450 mL per day) or green tea as a comparator for 2 weeks in a crossover design. Although creatinine-based eGFR was not affected after consuming either beverage, all cystatin-C-based eGFRs determined using five different equations were significantly increased after coffee consumption (means: 5.0-7.7%), but not after green tea consumption (means: 0.1-1.6%). Serum adiponectin and magnesium levels increased significantly after coffee consumption (means: 13.6% and 4.3%, resp.), but not after green tea consumption. These findings suggest that even a short period of coffee consumption may increase cystatin-C-based eGFR, along with favorable changes in serum adiponectin, in healthy young adults. PMID:21773013

  17. Prediction of Human Glomerular Filtration Rate from Preterm Neonates to Adults: Evaluation of Predictive Performance of Several Empirical Models.

    PubMed

    Mahmood, Iftekhar; Staschen, Carl-Michael

    2016-03-01

    The objective of this study was to evaluate the predictive performance of several allometric empirical models (body weight dependent, age dependent, fixed exponent 0.75, a data-dependent single exponent, and maturation models) to predict glomerular filtration rate (GFR) in preterm and term neonates, infants, children, and adults without any renal disease. In this analysis, the models were developed from GFR data obtained from inulin clearance (preterm neonates to adults; n = 93) and the predictive performance of these models were evaluated in 335 subjects (preterm neonates to adults). The primary end point was the prediction of GFR from the empirical allometric models and the comparison of the predicted GFR with measured GFR. A prediction error within ±30% was considered acceptable. Overall, the predictive performance of the four models (BDE, ADE, and two maturation models) for the prediction of mean GFR was good across all age groups but the prediction of GFR in individual healthy subjects especially in neonates and infants was erratic and may be clinically unacceptable. PMID:26801317

  18. A portable fiberoptic ratiometric fluorescence analyzer provides rapid point-of-care determination of glomerular filtration rate in large animals.

    PubMed

    Wang, Exing; Meier, Daniel J; Sandoval, Ruben M; Von Hendy-Willson, Vanessa E; Pressler, Barrak M; Bunch, Robert M; Alloosh, Mouhamad; Sturek, Michael S; Schwartz, George J; Molitoris, Bruce A

    2012-01-01

    Measurement of the glomerular filtration rate (GFR) is the gold standard for precise assessment of kidney function. A rapid, point-of-care determination of the GFR may provide advantages in the clinical setting over currently available assays. Here we demonstrate a proof of principle for such an approach in a pig and dogs, two species that approximate the vascular access and GFR results expected in humans. In both animal models, a sub-millimeter optical fiber that delivered excitation light and collected fluorescent emissions was inserted into a peripheral vein (dog) or central venous access (pig) by means of commercial intravenous catheters. A mixture of fluorescent chimeras of a small freely filterable reporter and large non-filterable plasma volume marker were infused as a bolus, excited by light-emitting diodes, and the in vivo signals detected and quantified by photomultiplier tubes in both species in less than 60 min. Concurrent standardized 6-h iohexol plasma kidney clearances validated the accuracy of our results for both physiologic and a chronic kidney disease setting. Thus, our ratiometric technique allows for both measurement of plasma vascular volume and highly accurate real-time GFR determinations, enabling clinical decision making in real time. PMID:21881552

  19. Subnormal Estimated Glomerular Filtration Rate Strongly Predict Incident Cardiovascular Events in Type 2 Diabetic Chinese Population With Normoalbuminuria

    PubMed Central

    Hsieh, Yi-Ting; Kuo, Jeng-Fu; Su, Shih-Li; Chen, Jung-Fu; Chen, Hung-Chun; Hsieh, Ming-Chia

    2016-01-01

    Abstract No study has evaluated whether subnormal estimated glomerular filtration rate (eGFR) (between 61 and 90 mL/min) and high normal albumin–creatinine ratio (ACR) (<30 mg/g) are associated with cardiovascular (CV) events and mortality in type 2 diabetic (T2DM) patients with normoalbuminuria. We observed a longitudinal cohort study of 1291 T2DM patients with normoalbuminuria who were receiving intensified multifactorial treatment from 2004 to 2008. Cox regression models were used to evaluate eGFR and ACR as the risk factors of major CV events (nonfatal myocardial infarction and stroke) and mortality. During the 4-year period, 56 patients died and 159 patients developed major CV events. We found eGFR, but not ACR, to be associated with major CV events. Compared to those with eGFR higher than 90 mL/min, patients with subnormal eGFR (HR: 3.133, 1.402–7.002, P = 0.005) were at greater risk of incident major CV events. Extremely low eGFR (<30 mL/min) was associated with mortality only in patients under 65 years old. Subnormal eGFR was a strong predictor of major CV events in diabetic patients with normoalbuminuria. Normoalbuminuric diabetic patients with subnormal eGFR may need intensive CV risk factor intervention to prevent and treat CV events. PMID:26765399

  20. Lower glomerular filtration rate is associated with higher systemic vascular resistance in patients without prevalent kidney disease.

    PubMed

    Vääräniemi, Kati; Koskela, Jenni; Tahvanainen, Anna; Tikkakoski, Antti; Wilenius, Matias; Kähönen, Mika; Kööbi, Tiit; Niemelä, Onni; Mustonen, Jukka; Pörsti, Ilkka

    2014-10-01

    The authors examined the association between estimated glomerular filtration rate (eGFR), calculated using the Chronic Kidney Disease Epidemiology Collaboration creatinine-cystatin C equation, and hemodynamics in 556 normotensive or never-treated hypertensive patients without kidney disease (mean age, 46 years). Hemodynamic variables were recorded using pulse wave analysis and whole-body impedance cardiography. The mean eGFR was 98 mL/min/1.73 m(2) (range, 64-145 mL/min/1.73 m(2) and one third of the patients had values below 92, while none had proteinuria. In linear regression analyses adjusted for differences in age, weight:height ratio, low-density lipoprotein cholesterol, and sex, significant associations were found between lower eGFR and higher systolic (P=.001) and diastolic blood pressure (P<.001) and higher systemic vascular resistance (P=.001). There was no association between eGFR and cardiac output or extracellular volume. In the absence of clinical kidney disease, lower eGFR was associated with higher blood pressure and systemic vascular resistance. Therefore, early impairment in kidney function may be involved in the pathogenesis of essential hypertension. PMID:25228202

  1. Prevalence and Determinants of Chronic Kidney Disease Among Hypertensive Cameroonians According to Three Common Estimators of the Glomerular Filtration Rate.

    PubMed

    Kaze, Francois Folefack; Kengne, Andre-Pascal; Magatsing, Carine Tchendjou; Halle, Marie-Patrice; Yiagnigni, Euloge; Ngu, Kathleen Blackett

    2016-05-01

    Hypertension is a risk factor for renal diseases, which, in turn, are precursors of hypertension. The authors assessed the prevalence and determinants of chronic kidney disease (CKD) among 336 hypertensive adult Cameroonians (mean age, 60.9±11.3 years; 63.4% women) at Yaoundé. Any participant with an estimated glomerular filtration rate <60 mL/min/1.73 m(2) regardless of the equation used (Cockcroft-Gault [CG], Modification of Diet in Renal Disease [MDRD], and Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI]) and/or dipstick proteinuria was reviewed 3 months later. Participants presented a high prevalence of diabetes (18.5%), dyslipidemia (17.6%), gout/hyperuricemia (10.7%), overweight/obesity (68.8%), self-medication (37.5%), and alcohol consumption (33.3%). Hypertension was uncontrolled in 265 patients (78.9%). The prevalence of CKD was 49.7%, 50.0%, and 52.1% according to MDRD, CKD-EPI, and CG equations, respectively. Advanced age, adiposity, and severity of hypertension were determinants of CKD. Nearly half of the hypertensive patients had CKD regardless of the estimators used, predicted by well-known risk factors. PMID:26791352

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

    PubMed Central

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

    2014-01-01

    Background It is well known that hypertension may cause glomerular damage, but the molecular mechanisms involved are still incompletely understood. Methods 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. Results 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. Conclusions 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. PMID:25129444

  3. Mechanisms underlying transition from acute glomerular injury to late glomerular sclerosis in a rat model of nephrotic syndrome.

    PubMed Central

    Anderson, S; Diamond, J R; Karnovsky, M J; Brenner, B M

    1988-01-01

    Functional and morphologic measurements were performed in Munich-Wistar rats after a single central venous injection of puromycin aminonucleoside (PA) or saline vehicle (sham). During phase I, PA rats exhibited overt nephrotic syndrome and impaired glomerular filtration, primarily due to a reduction in the glomerular capillary ultrafiltration coefficient. The morphologic counterpart of the latter consisted of effacement of glomerular epithelial cell foot processes and decrease in the number of filtration slit diaphragms. Administration of the angiotensin I converting enzyme inhibitor (CEI) enalapril to PA rats did not ameliorate glomerular dysfunction. During phase II, PA rats exhibited spontaneous resolution of proteinuria, impaired function, and morphologic abnormalities. However, PA rats now demonstrated marked glomerular capillary hypertension and continued, albeit lesser, reductions in the ultrafiltration coefficient. Concurrent CEI administration modestly lowered systemic arterial pressure, and normalized the glomerular capillary hydraulic pressure and ultrafiltration coefficient. Additional rats were studied during phase III, 70 wk after injection. In PA rats, prior glomerular hypertension was associated with development of recurrent proteinuria and extensive glomerular sclerosis, whereas concurrent CEI administration limited these parameters to values comparable to those in sham rats. Glomerular hypertension thus may explain the development of glomerular sclerosis and renal failure long after an episode of acute glomerular injury. Images PMID:2846658

  4. Comparison of glomerular filtration rate measured between anterior and posterior image processing using Gates’ method in an ectopic pelvic kidney

    PubMed Central

    Li, Na; Li, Baojun; Liang, Wenli

    2016-01-01

    Objective The aim of this study was to evaluate the difference in measured glomerular filtration rate (GFR) of an ectopic pelvic kidney between anterior and posterior image processing using Gates’ method of renal dynamic imaging. Methods A total of 10 patients were studied retrospectively, with a single ectopic kidney in the pelvic cavity and a contralateral kidney at its normal anatomical position confirmed by ultrasound, computed tomography, renal dynamic imaging, etc. All images of ectopic kidneys were processed, and GFRs were measured using anterior and posterior Gates’ method of renal dynamic imaging, respectively. The contralateral normal kidney was only processed on posterior imaging. The total GFRant of one patient, which was equal to the sum of the GFR of a normal kidney on posterior imaging and the GFR of an ectopic kidney on anterior imaging, was compared with the total GFRpost of two kidneys on posterior imaging, with the GFRtwo-sample from the two-sample method, and with the estimated GFR in the Chronic Kidney Disease Epidemiology Collaboration equation. All correlation analyses were carried out between GFRs obtained from three methods, and all patients were followed up. For statistical analysis, nonparametric rank tests were used, Bland-Altman graphs were plotted. Results The mean GFR of the ectopic kidney on anterior imaging was 27.48±12.24 ml/min/1.73 m2. It was higher than the GFR (10.71±4.74 ml/min/1.73 m2) on posterior imaging (t=−2.803, P<0.05). There were statistical differences between the total GFRant and the total GFRtwo-sample (Z=−2.295, P<0.05), between the total GFRant and the total GFRpost (Z=2.599, P<0.01), between the total GFRtwo-sample and the total GFRpost (Z=−2.191, P<0.05), and between the total GFRant and the estimated glomerular filtration rate (Z=−2.803, P<0.01). The bias of the total GFRant was different from that of the total GFRpost (Z=−2.191, P<0.05). There were no differences in the precision and

  5. The relationship between some plasma clearance methods for estimation of glomerular filtration rate in dogs with pyometra.

    PubMed

    Heiene, R; Moe, L

    1999-01-01

    The purpose of the present study was to compare different pharmacokinetic models for estimation of glomerular filtration rate (GFR) in 50 dogs with pyometra. GFR was estimated by plasma clearance (CLplasma) of iohexol by four 1-compartment methods (CL1c), a 2-compartment method (CL2c), and the trapezoidal method (CLtr). Regression analysis was performed to establish correction formulas for prediction of CLtr from the CL1c values and to find optimal times of sampling. Standardization of clearance values to body weight (kg), body surface area (m2) and extracellular fluid volume (ECFV) was compared by ranking of values. CLtr and CL2c values were similar, whereas CL1c overestimated CLtr. CLtr could be predicted from 2 samples at 2 and 3 hours after injection, using the formula CLtr = 4.52 + 0.84CL1c - 0.00080(CL1c)2 (R2 = .97). Similar relationships were found when sampling at 2 and 4 hours or at 2, 3 and 4 hours after injection, whereas predictions from the 3- and 4-hour estimates were not optimal (R2 = .79). The 2-sample methods for calculating GFR/ECFV generally produced unreliable predictions of the complete curve GFR/ECFV values. For some dogs, the choice of standardization procedure substantially changed the apparent level of renal function relative to other dogs in the study. We conclude that by applying an appropriate correction formula, GFR may be estimated using 2 blood samples at 2 and 3, or 2 and 4 hours after injection of iohexol when renal function is normal or moderately reduced. The method of standardizing the analysis with respect to body size may influence interpretation of the results substantially. PMID:10587261

  6. Low glomerular filtration rate is a risk factor for ribavirin-associated anaemia in old patients with chronic hepatitis C.

    PubMed

    Borroni, G; Cazzaniga, M; Andreoletti, M; Ceriani, R; Guerzoni, P; Omazzi, B; Pich, M G L; Prada, A; Spinzi, G; Terreni, N; Salerno, F

    2013-04-01

    Elderly patients with chronic hepatitis C have a reduced responsiveness to antiviral therapy with Peg-interferon and ribavirin. The dose reduction or the discontinuation of ribavirin due to the occurrence of anaemia is one of the most important causes for the low sustained viral response observed in older patients. We aimed to evaluate the relationship between baseline renal function and the early onset of ribavirin-associated anaemia in older (≥60 years) patients. Using data from 348 patients with chronic hepatitis C consecutively treated with peg-interferon plus ribavirin, we investigated which factors were associated with the occurrence of anaemia in elderly patients (≥60 years). Ribavirin-induced anaemia occurred in 40.5% of patients. Older patients showed a rate of anaemia significantly higher than younger patients (51.5% vs 36.3%; P = 0.009). Consequently, the rate of ribavirin dose reduction or discontinuation due to anaemia was 35.1% in older patients and 23.5% in younger patients (P = 0.029). A significantly higher proportion of older patients had a low baseline glomerular filtration rate (GFR) compared with younger patients (56.7% vs 27.1%; P < 0.001). At the multivariate regression analysis, low baseline GFR (<70 mL/min) was associated with an increased risk of ribavirin-associated anaemia only in the older patients (OR: 3.526; 95% CI: 1.385-8.979; P = 0.008). In this subset, baseline GFR was significantly correlated with both absolute (r = -0.320; P < 0.001) and relative (r = -0.324; P < 0.001) haemoglobin decrease within the first 8 weeks of treatment. In patients aged >60 years, a low pre-treatment GFR was strongly associated with the risk to develop ribavirin-related anaemia with consequent reduction in ribavirin doses. PMID:23490395

  7. Outcome assessment of a computer-animated model for learning about the regulation of glomerular filtration rate.

    PubMed

    Gookin, Jody L; McWhorter, Dan; Vaden, Shelly; Posner, Lysa

    2010-06-01

    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) participated in separate online exercises to evaluate the use of a computer-animated model of GFR regulation (www.aamc.org/mededportal) on learning outcome. Students were randomly allocated to study either the animated model or written materials before completion of a 10-question multiple-choice quiz. House officers completed a 35-question test before and after study of the animated model. Both groups completed a survey about the learning exercise. The ability of the model to enhance learning was demonstrated by a significant improvement (P < 0.001) in the test performance of house officers after studying the model. The model performed similarly to written materials alone in affecting the subsequent quiz performance of the students. The majority of students and house officers agreed or strongly agreed that the animated model was easy to understand, improved their knowledge and appreciation of the importance of GFR regulation, and that they would recommend the model to peers. Most students [63 of 76 students (83%)] responded that they would prefer the use of the animated model alone over the study of written materials but acknowledged that a combination of hardcopy written notes and the animated model would be ideal. A greater applicability of the model to more advanced students and an introduction in a didactic setting before individual study were suggested by the house officers. The results of this study suggest that the animated model is a useful, effective, and well-received tool for learning and creating a visual memory of the regulatory mechanisms of GFR. PMID:20522905

  8. Estimation of glomerular filtration rate in healthy cats using single-slice dynamic CT and Patlak plot analysis.

    PubMed

    Granger, L Abbigail; Armbrust, Laura J; Rankin, David C; Ghering, Ronette; Bello, Nora M; Alexander, Kate

    2012-01-01

    Commonly used clinical indicators of renal disease are either insensitive to early dysfunction or have delayed results. Decreased glomerular filtration rate (GFR) indicates renal dysfunction before there is a loss of 50% of functional nephrons. Most tests evaluate global rather than individual kidney function. Dynamic computed tomography (CT) and Patlak plot analysis allows for individual GFR to be tested. Our objectives were to establish a procedure and provide reference values for determination of global GFR in 10 healthy cats using dynamic CT (CTGFR). This method of GFR determination was compared against serum iohexol clearance (SIC). A single CT slice centered on both kidneys and the aorta was acquired every fifth second during and after a bolus injection of iohexol (240 mgI/ml; 300 mgI/kg) for 115 s. Using data from this dynamic acquisition, Patlak plots were obtained, GFR was calculated, and results were compared to global GFR determined by iohexol clearance. The average global CTGFR estimate was 1.84 ml/min x kg (SD = 0.43; range = [1.22, 2.45]). The average global GFR measured using SIC was 2.45 ml/min x kg (SD = 0.58; range = [1.72, 3.69]). GFR measurements estimated by both dynamic CT and SIC were positively associated (estimated Spearman rank correlation coefficient = 0.72; P = 0.0234). The CTGFR method consistently underestimated GFR with a bias of -0.62 (SE = 0.1307) when compared to SIC (P = 0.0011). In healthy cats, CTGFR was capable of determining individual kidney function and appears clinically promising. PMID:22182065

  9. Glomerular Filtration Rate and Urine Albumin to Creatinine Ratio Associated With Hearing Impairment Among Korean Adults With Diabetes

    PubMed Central

    Cho, Yunji; Kim, Do Hoon; Choi, June; Lee, Joo Kyung; Roh, Yong-Kyun; Nam, Hyo-Yun; Nam, Ga-Eun; Kim, Dong-Won; Lee, Seung-Hyun; Lee, Chung-Woo; Han, Kyungdo; Park, Yong-Gyu

    2016-01-01

    Abstract The objective of this study was to examine the association of estimated glomerular filtration rate (eGFR) and urine albumin to creatinine ratio (ACR) with hearing impairment among diabetic adults in Korea. The study was based on data from Korea National Health and Nutrition Examination Survey 2011 to 2012. Participants were 1206 diabetic adults, aged over 19 years, who completed audiometric testing supervised by nationally certified clinicians. Hearing impairment was defined in three grades: no hearing impairment (pure-tone average 0–25 dB), slight hearing impairment (26–40 dB), and disabling hearing impairment (>40 dB) in the better ear at frequencies 0.5, 1, 2, 3, 4 and 6 kHz. Using logistic regression, risk of hearing impairment was assessed after having controlled for confounding factors. Higher levels of ACR and lower levels of eGFR correlated with an increase in percentage of disabling hearing impairment both unilaterally and bilaterally (P < 0.001). Controlling for possible confounding covariates, odds ratios for hearing impairment showed tendency to increase in higher ACR groups (P for trend = 0.029). Similar pattern was examined between eGFR and hearing impairment (P for trend = 0.006). Odds ratios were 1.981 (1.146, 3.424) for ACR Q4 and 2.773 (1.286, 5.983) for eGFR < 60 mL/min. Fall in eGFR and rise in ACR correlated with severity of hearing impairment. The association existed independently of age, sex, body mass index (BMI), smoking, drinking, exercise, new onset of diabetes, education, income, mental stress, noise exposure, and metabolic syndrome. PMID:27124027

  10. The impairment of true glomerular filtration rate in long-term cyclosporine-treated pediatric allograft recipients

    SciTech Connect

    McDiarmid, S.V.; Ettenger, R.B.; Hawkins, R.A.; Senguttvan, P.; Busuttil, R.W.; Vargas, J.; Berquist, W.E.; Ament, M.E.

    1990-01-01

    We performed indium-111-DTPA plasma clearance studies in 61 pediatric kidney and liver recipients treated with cyclosporine to compare true glomerular filtration rate with calculated GFR (cGFR). The mean true GFR of 61.9 +/- 36.6 ml/min/1.73 m2 indicated renal impairment. The mean cGFR of 85.2 +/- 22.4 ml/min/1.73 m2 was significantly higher (P less than 0.001), and overestimated GFR by 38%. cGFR alone did not accurately reflect the degree of renal dysfunction. A group of 48 pediatric orthotopic liver transplant recipients was studied in more detail: 73% of these patients had a true GFR less than 70 ml/min/1.73 m2, while 85% had a true GFR below 90 ml/min/1.73 m2, the lower limit for normal GFR in children. The mean true GFR for patients treated more than 24 months with CsA was lower (P = 0.02) than patients treated with CsA for 12 to 24 months. OLT patients with normal true GFR (greater than 90 ml/min/1.73 m2) had significantly lower plasma CsA levels, and 50% of patients with a true GFR less than or equal to 50 ml/min/1.73 m2 had hypertension. There was no effect on true GFR of age, liver function, azathioprine use, or peritransplant treatment with other nephrotoxic drugs. We conclude that true GFR is significantly impaired in long-term CsA-treated allograft pediatric recipients. Calculations of GFR underestimate the degree of renal dysfunction. As patients treated greater than 24 months had the lowest true GFRs, the fall in GFR may be progressive.

  11. Factors Affecting Glomerular Filtration Rate, as Measured by Iohexol Disappearance, in Men with or at Risk for HIV Infection

    PubMed Central

    Margolick, Joseph B.; Jacobson, Lisa P.; Schwartz, George J.; Abraham, Alison G.; Darilay, Annie T.; Kingsley, Lawrence A.; Witt, Mallory D.; Palella, Frank J.

    2014-01-01

    Objective Formulae used to estimate glomerular filtration rate (GFR) underestimate higher GFRs and have not been well-studied in HIV-infected (HIV(+)) people; we evaluated the relationships of HIV infection and known or potential risk factors for kidney disease with directly measured GFR and the presence of chronic kidney disease (CKD). Design Cross-sectional measurement of iohexol-based GFR (iGFR) in HIV(+) men (n = 455) receiving antiretroviral therapy, and HIV-uninfected (HIV(−)) men (n = 258) in the Multicenter AIDS Cohort Study. Methods iGFR was calculated from disappearance of infused iohexol from plasma. Determinants of GFR and the presence of CKD were compared using iGFR and GFR estimated by the CKD-Epi equation (eGFR). Results Median iGFR was higher among HIV(+) than HIV(−) men (109 vs. 106 ml/min/1.73 m2, respectively, p = .046), and was 7 ml/min higher than median eGFR. Mean iGFR was lower in men who were older, had chronic hepatitis C virus (HCV) infection, or had a history of AIDS. Low iGFR (≤90 ml/min/1.73 m2) was associated with these factors and with black race. Other than age, factors associated with low iGFR were not observed with low eGFR. CKD was more common in HIV(+) than HIV(−) men; predictors of CKD were similar using iGFR and eGFR. Conclusions iGFR was higher than eGFR in this population of HIV-infected and -uninfected men who have sex with men. Presence of CKD was predicted equally well by iGFR and eGFR, but associations of chronic HCV infection and history of clinically-defined AIDS with mildly decreased GFR were seen only with iGFR. PMID:24516530

  12. Influence of Weight-Age Normalization on Glomerular Filtration Rate Values of Renal Patients: A STROBE-Compliant Article.

    PubMed

    Li, Li; Hongwei, Si; Ying, Qiao; Jianzhong, Liu; Zhifang, Wu; Ling, Gao; Sijin, Li

    2016-01-01

    To explore whether weight-age (W-A) could be applied in clinical practice, this study was designed to verify the normalization ability of W-A by the data from another medical center, and to access the influence of the normalization on glomerular filtration rate (GFR) values in renal patients.Both plasma clearance (pGFR) and camera-based (gGFR), which were separately scaled to W-A and body surface area (BSA), were measured for patients with diffuse renal diseases. The patients (n = 298) were stratified according to the Chinese body mass index (BMI) criteria and were staged according to the Kidney Disease Outcome Quality Initiatives guideline based on gGFR and pGFR separately.The indices of intraclass correlation coefficient (ICC), concordance correlation coefficient (CCC), and ratio of residual standard deviation to pooled standard deviation (RSD/PSD) suggested that, for all patients and each BMI stratum, W-A was obviously better than BSA in scaling GFR. Both under pGFR or gGFR renal stages, only small amount of the patients encountered stage migrations from BSA to W-A scaled stages. The differences between any 2 of the unscaled, BSA scaled, and W-A scaled gGFR (or pGFR) were not obviously changed. Additionally, in some strata, W-A normalization is better than BSA normalization in decreasing the median bias between pGFR and gGFR.W-A is better than BSA in scaling GFR without obvious modifying GFR values and can be applied in routine clinical practice. PMID:26817886

  13. Assessing Glomerular Filtration Rate in Hospitalized Patients: A Comparison Between CKD-EPI and Four Cystatin C-Based Equations

    PubMed Central

    de la Torre, Judith; Ramos, Natalia; Quiroz, Augusto; Garjau, Maria; Torres, Irina; Azancot, M. Antonia; López, Montserrat; Sobrado, Ana

    2011-01-01

    Summary Background and objectives A specific method is required for estimating glomerular filtration rate GFR in hospitalized patients. Our objective was to validate the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation and four cystatin C (CysC)–based equations in this setting. Design, setting, participants, & measurements This was an epidemiologic, cross-sectional study in a random sample of hospitalized patients (n = 3114). We studied the accuracy of the CKD-EPI and four CysC-based equations—based on (1) CysC alone or (2) adjusted by gender; (3) age, gender, and race; and (4) age, gender, race, and creatinine, respectively—compared with GFR measured by iohexol clearance (mGFR). Clinical, biochemical, and nutritional data were also collected. Results The CysC equation 3 significantly overestimated the GFR (bias of 7.4 ml/min per 1.73 m2). Most of the error in creatinine-based equations was attributable to calculated muscle mass, which depended on patient's nutritional status. In patients without malnutrition or reduced body surface area, the CKD-EPI equation adequately estimated GFR. Equations based on CysC gave more precise mGFR estimates when malnutrition, extensive reduction of body surface area, or loss of muscle mass were present (biases of 1 and 1.3 ml/min per 1.73 m2 for equations 2 and 4, respectively, versus 5.9 ml/min per 1.73 m2 for CKD-EPI). Conclusions These results suggest that the use of equations based on CysC and gender, or CysC, age, gender, and race, is more appropriate in hospitalized patients to estimate GFR, since these equations are much less dependent on patient's nutritional status or muscle mass than the CKD-EPI equation. PMID:21852668

  14. Abnormal development of glomerular endothelial and mesangial cells in mice with targeted disruption of the lama3 gene.

    PubMed

    Abrass, C K; Berfield, A K; Ryan, M C; Carter, W G; Hansen, K M

    2006-09-01

    Mice with targeted disruption of the lama3 gene, which encodes the alpha3 chain of laminin-5 (alpha3beta3gamma2, 332), develop a blistering skin disease similar to junctional epidermolysis bullosa in humans. These animals also develop abnormalities in glomerulogenesis. In both wild-type and mutant animals (lama3(-/-)), podocytes secrete glomerular basement membrane and develop foot processes. Endothelial cells migrate into this scaffolding and secrete a layer of basement membrane that fuses with the one formed by the podocyte. In lama3(-/-) animals, glomerular maturation arrests at this stage. Endothelial cells do not attenuate, develop fenestrae, or form typical lumens, and mesangial cells (MCs) were not identified. LN alpha3 subunit (LAMA3) protein was identified in the basement membrane adjacent to glomerular endothelial cells (GEnCs) in normal rats and mice. In developing rat glomeruli, the LAMA3 subunit was first detectable in the early capillary loop stage, which corresponds to the stage at which maturation arrest was observed in the mutant mice. Lama3 mRNA and protein were identified in isolated rat and mouse glomeruli and cultured rat GEnCs, but not MC. These data document expression of LAMA3 in glomeruli and support a critical role for it in GEnC differentiation. Furthermore, LAMA3 chain expression and/or another product of endothelial cells are required for MC migration into the developing glomerulus. PMID:16850021

  15. The role of cystatin-C in the confirmation of reduced glomerular filtration rate among the oldest old

    PubMed Central

    Colantonio, Lisandro D.; Tanner, Rikki M.; Warnock, David G.; Gutiérrez, Orlando M.; Judd, Suzanne; Muntner, Paul

    2016-01-01

    Introduction Current guidelines suggest using cystatin-C to confirm a reduced creatinine-based estimated glomerular filtration rate (eGFRcr) when the latter is thought to be inaccurate. Older adults have reduced muscle mass, which may affect the accuracy of eGFRcr. We evaluated the use of cystatin-C-based eGFR (eGFRcys) to confirm reduced eGFRcr among adults ≥ 80 years of age and, for comparison, younger adults. Material and methods We analyzed data from 3,059 REasons for Geographic And Racial Differences in Stroke (REGARDS) study participants with reduced eGFRcr (< 60 ml/min/1.73 m2) enrolled in 2003–2007 who were not on dialysis. eGFRcr and eGFRcys were calculated using age, sex and race-adjusted equations. Confirmed reduced eGFRcr was defined as eGFRcys < 60 ml/min/1.73 m2. Prevalence of chronic kidney disease complications at baseline and all-cause mortality up to March 2012 were calculated. Analyses were stratified by age: < 65, 65–79 and ≥ 80 years. Results Among participants < 65, 65–79 and ≥ 80 years of age, 76.5%, 85.7% and 92.5%, respectively, had reduced eGFRcr confirmed with eGFRcys (p < 0.001). Among participants ≥ 80 years of age, those with reduced eGFRcr confirmed with eGFRcys had higher prevalence of hypertension (79.1% vs. 65.1%, p = 0.03) and albuminuria (38.3% vs. 22.7%, p = 0.04) and higher risk for all-cause mortality (hazard ratio: 2.43; 95% confidence interval: 1.19–5.01) as compared with those in whom reduced eGFRcr was not confirmed by eGFRcys. Conclusions Reduced eGFRcr was confirmed using eGFRcys for the vast majority of adults ≥ 80 years. These results suggest that using cystatin-C to confirm a reduced eGFRcr may not be necessary among the oldest old. PMID:26925119

  16. A Low Baseline Glomerular Filtration Rate Predicts Poor Clinical Outcome at 3 Months after Acute Ischemic Stroke

    PubMed Central

    Kim, Hyung Jik; Kim, Jwa-Kyung; Oh, Mi Sun; Kim, Sung Gyun; Yu, Kyung-Ho

    2015-01-01

    Background and Purpose Chronic kidney disease (CKD) is an established risk factor for numerous cardiovascular diseases including stroke. The relationship between the baseline estimated glomerular filtration rate (eGFR) and clinical 3-month outcomes in patients with acute ischemic stroke were evaluated in this study. Methods This was a prospective cohort study involving a hospital-based stroke registry; 1373 patients with acute ischemic stroke were enrolled. Patients were divided into the following four groups according their eGFR (calculated using the CKD Epidemiology Collaboration equations): ≥60, 45-59, 30-44, and <30 mL/min/1.73 m2. The primary endpoint of poor functional outcome was defined as 3-month death or dependency (modified Rankin Scale score ≥3); secondary endpoints were neurological deterioration (increase in National Institutes of Health Stroke Severity score of ≥4 at discharge compared to baseline) during hospitalization and in-hospital mortality. Results The overall eGFR was 84.5±20.8 mL/min/1.73 m2 (mean±SD). The distribution of baseline renal impairment was as follows: 1,218, 82, 40, and 33 patients had eGFRs of ≥60, 45-59, 30-44, and <30 mL/min/1.73 m2, respectively. At 3 months after the stroke, 476 (34.7%) patients exhibited poor functional outcome. Furthermore, a poor functional outcome occurred more frequently with increasingly advanced stages of CKD (rates of 31.9%, 53.7%, 55.0%, and 63.6% for CKD stages 1/2, 3a, 3b, and 4/5, respectively; p<0.001). Multivariate analysis revealed that a baseline eGFR of <30 mL/min/1.73m2 increased the risk of a poor functional outcome by 2.37-fold (p=0.047). In addition, baseline renal dysfunction was closely associated with neurological deterioration during hospitalization and with in-hospital mortality. Conclusions A low baseline eGFR was strongly predictive of both poor functional outcome at 3 months after ischemic stroke and neurological deterioration/mortality during hospitalization. PMID

  17. Effect of Vitamin D Receptor Activators on Glomerular Filtration Rate: A Meta-Analysis and Systematic Review

    PubMed Central

    Chen, Jing

    2016-01-01

    Background Vitamin D receptor activators (VDRAs) can protect against mineral bone disease, but they are reported to elevate serum creatinine (SCr) and may also reduce glomerular filtration rate (GFR). Methods We conducted a systematic review and meta-analysis of randomized clinical trials (RCTs) to evaluate the effect of VDRAs on kidney function and adverse events. MEDLINE, EMBASE, the Cochrane Controlled Trials Register were searched for RCTs that evaluate vitamin D receptor activators (alfacalcidol, calcitriol, doxercalciferol, falecalcitriol, maxacalcitol and paricalcitol) up to March 2015. Results We included 31 studies, all of which were performed between 1976 and 2015, which enrolled 2621 patients. Patients receiving VDRAs had lower eGFR (weighted mean difference WMD -1.29 mL/min /1.73 m2, 95% CI -2.42 to -0.17) and elevated serum creatinine (WMD 7.03 μmol/L, 95% CI 0.61 to 13.46) in sensitivity analysis excluding studies with dropout rate more than 30%. Subgroup analysis of the 5 studies that not use SCr-based measures did not indicated lower GFR in the VDRAs group(WMD -0.97 mL/min/1.73 m2, 95% CI -4.85 to 2.92). Compared with control groups, there was no difference in all-cause mortality (relative risk RR 1.41, 95% CI 0.58 to 3.80), cardiovascular disease (RR 0.84, 95% CI 0.42 to 1.71), and severe adverse events (RR 1.15, 95% CI 0.75 to 1.77) for the VDRAs groups. Episodes of hypercalcemia (RR 3.29, 95% CI 2.02 to 5.38) were more common in the VDRAs group than in the control group. Conclusions Administration of VDRAs increased serum creatinine levels. Subgroup analysis of studies that did not use SCr-based measures did not indicate a lower GFR in the VDRA group. Future studies with non-SCr-based measures are needed to assess whether the mild elevations of serum creatinine are of clinical significance. PMID:26812502

  18. Comparison of plasma clearance of exogenous creatinine, exo-iohexol, and endo-iohexol over a range of glomerular filtration rates expected in cats.

    PubMed

    van Hoek, Ingrid M; Lefebvre, Hervé P; Paepe, Dominique; Croubels, Siska; Biourge, Vincent; Daminet, Sylvie

    2009-12-01

    The study investigated plasma clearance of exogenous creatinine (PECCT), exo-iohexol (PexICT) and endo-iohexol (PenICT) in six healthy cats, four cats with chronic kidney disease (CKD) and six hyperthyroid (HT) cats to assess potential differences in glomerular filtration rate (GFR) measurement over a wide range of GFR values. The PECCT, PexICT and PenICT were performed in a combined protocol. There was a significant difference between PexICT and PenICT and PECCT in healthy cats. Differences between clearance techniques are suggested to be correlated to range in GFRs and should be taken into account when GFR is measured. PMID:19679501

  19. Canine Systemic Lupus Erythematosus. TRANSMISSION OF SEROLOGIC ABNORMALITIES BY CELL-FREE FILTRATES

    PubMed Central

    Lewis, Robert M.; Andre-Schwartz, Janine; Harbis, Gerald S.; Hirsch, Martin S.; Black, Paul H.; Schwartz, Robert S.

    1973-01-01

    The presence of viruses was sought in a colony of dogs bred from parents with systemic lupus crythematosus (SLE). Cell-free filtrates prepared from the spleens of these animals were injected into newborn dogs, mice, and rats. The canine recipients developed antinuclear antibody (ANA) and positive lupus erythematosus (LE) cell tests: ANA and, in some cases, antinative DNA antibodies were produced by the murine recipients: no abnormalities were detected in the rats. Serial passage of spleen cells or cell-free filtrates of spleen tissue in syngeneic mice reduced the time required for appearance of ANA from 9 to 4 mo. Some murine recipients of the canine filtrate developed malignant lymphomas. Murine leukemia viruses were identified in these tumors by electron microscopic, virologic, and serologic technics. These neoplasms, but not other tumors known to contain murine leukemia viruses, were associated with the production of ANA. Puppies inoculated with the canine filtrate-induced mouse lymphoma developed ANA and positive LE cell tests within 4 mo. The results were interpreted to indicate the presence in canine SLE of a virus capable of: (a) inducing the serologic abnormalities of SLE in normal dogs and mice: (b) activating latent murine leukemia viruses: and (c) spreading by both horizonal and vertical routes. Images PMID:4124208

  20. Ramadan fasting and chronic kidney disease: does estimated glomerular filtration rate change after and before Ramadan? Insights from a mini meta-analysis

    PubMed Central

    Bragazzi, Nicola Luigi

    2015-01-01

    Ramadan fasting represents one of the five pillars of the Islam creed. Even though patients are exempted from this religious duty, they may be eager to share this particular moment of the year with their family and peers, taking part in the intense spiritual ceremonies and events that characterize this month. However, there are no guidelines or standardized protocols that can help physicians to properly address the issue of patients with chronic kidney disease fasting in Ramadan and correctly advising them. For this purpose, we carried out a systematic review and a meta-analysis to see whether glomerular filtration rate value changed before and after Ramadan. Our main findings are that: chronic kidney disease patients can safely fast during Ramadan since glomerular filtration rate does not change in a statistically significant way and, even though most studies have been carried out during Ramadan falling in cold seasons, the sensitivity analysis did not reveal any impact of seasonality. Further research in the field is needed. PMID:26082658

  1. Additive effect of polymorphisms in the β2 -adrenoceptor and NADPH oxidase p22 phox genes contributes to the loss of estimated glomerular filtration rate in Chinese.

    PubMed

    Wang, Tao; Zhang, Yan; Ma, JingTao; Feng, Zhen; Niu, Kai; Liu, Bing

    2014-09-01

    Because increased oxidative stress may mediate the detrimental actions of enhanced sympathetic nervous activity on renal function and vice versa, we investigated the effect of the polymorphic Arg16Gly in the β2 -adrenoceptor (ADRB2) gene, Trp64Arg in the β3 -adrenoceptor (ADRB3) gene and C242T in the NADPH oxidase p22phox (CYBA) gene on estimated glomerular filtration rate (eGFR) in a Chinese population. Initially recruited from different outpatient services of HeBei General Hospital in northern China, 668 individuals were finally included in the study, with complete demographic information. Laboratory tests were performed and estimated glomerular filtration rate (eGFR) was derived from the Modification of Diet in Renal Disease (MDRD) equation for the Chinese population. Plasma noradrenaline levels and genotype were determined by HPLC and the TaqMan method, respectively. Only across the Arg16Gly polymorphism did eGFR show significant difference: it was lower in individuals with the Gly16Gly variation, who also had the highest plasma noradrenaline levels. This polymorphism remained a significant determinant of eGFR after multivariate analysis. Of importance, the multifactor dimensionality reduction method further detected a significant synergism between the Arg16Gly and C242T polymorphisms in reducing eGFR. These observations clarify the effects of the studied polymorphisms on eGFR and exemplify gene-gene interactions influencing renal function. PMID:24890187

  2. Effects of Moderate-to-Severe Impairment of the Estimated Glomerular Filtration Rate and of Proteinuria on the Central Hemodynamics and Arterial Stiffness in Middle-Aged Healthy Japanese Men

    PubMed Central

    Tomiyama, Hirofumi; Odaira, Mari; Matsumoto, Chisa; Yamada, Jiko; Yoshida, Masanobu; Shiina, Kazuki; Yamashina, Akira

    2011-01-01

    We evaluated the effects of moderate-to-severe impairment of the estimated glomerular filtration rate (eGFR: 15 to 59 mL/min per 1.73 m2) and of proteinuria on the central hemodynamics and the pulse wave velocity (PWV) in 2244 middle-aged healthy Japanese men who were not receiving any medications for cardiovascular diseases or cardiovascular risk factors. The adjusted value of the radial augmentation index was higher in the subjects with proteinuria than in those without proteinuria. On the other hand, this value was similar between the subjects with and without moderate-to-severe impairment of the eGFR. Not only proteinuria but also moderate-to-severe impairment of the eGFR was associated with increase in the adjusted value of the brachial-ankle PWV. Thus, proteinuria was found to be an independent risk factor for abnormal central hemodynamics and increased stiffness of the large- to middle-sized arteries, while moderate-to-severe impairment of the eGFR was associated with an increase of the arterial stiffness, but not with abnormality of the central hemodynamics. PMID:21423551

  3. Measurement of glomerular filtration rate in homozygous sickle cell disease: a comparison of 51Cr-EDTA clearance, creatinine clearance, serum creatinine and beta 2 microglobulin.

    PubMed Central

    Aparicio, S A; Mojiminiyi, S; Kay, J D; Shepstone, B J; de Ceulaer, K; Serjeant, G R

    1990-01-01

    Glomerular filtration rates (GFR) were measured with 51Cr-EDTA in 38 patients (aged 40-75 years) with homozygous sickle cell disease and compared with serum beta 2 microglobulin concentrations in 38 patients and with creatinine clearance in 21 patients. GFR estimated with 51Cr-EDTA was closely correlated with single serum creatinine measurements and the inverse of serum beta 2 microglobulin. Creatinine clearance was also found to be correlated, but values were, on average, 32% below those obtained by the 51Cr-EDTA method, and this difference was significant. It is concluded that measurements of beta 2 microglobulin, single serum creatinine, and creatinine clearance are valuable indicators of GFR in homozygous sickle cell disease. Measurement of beta 2 microglobulin was a useful and reliable method of estimating GFR from single plasma measurements and is therefore a useful means of screening the population. PMID:2115049

  4. Temporal behavior of peripheral organ distribution volume in mammillary systems. II. Application to background correction in separate glomerular filtration rate estimation in man

    SciTech Connect

    Decostre, P.L.; Salmon, Y. )

    1990-10-01

    An original approach to background subtraction is presented for 99mTc-DTPA separate glomerular filtration rate (SGFR) estimation in man. The method is based on the properties of the peripheral organ distribution volume (PODV) in mammillary systems. These PODV properties allow easy separation of the components of the renogram, i.e., interstitial fluid, plasma and renal activities. The proposed algorithm takes advantage of the linear time dependence of the kidney distribution volume, during the renal uptake phase, to correct for the plasma residual activity, which always remains after classical background correction. Theoretically, the ratio between kidney uptake and SGFR should be identical for both left and right kidneys, even for very asymmetrical kidney functions. This is best verified when the proposed plasma residual activity correction is applied.

  5. Genotype/phenotype correlations of NPHS1 and NPHS2 mutations in nephrotic syndrome advocate a functional inter-relationship in glomerular filtration.

    PubMed

    Koziell, Ania; Grech, Victor; Hussain, Sagair; Lee, Gary; Lenkkeri, Ulla; Tryggvason, Karl; Scambler, Peter

    2002-02-15

    Mutations of the novel renal glomerular genes NPHS1 and NPHS2 encoding nephrin and podocin cause two types of severe nephrotic syndrome presenting in early life, Finnish type congenital nephrotic syndrome (CNF) and a form of autosomal recessive familial focal segmental glomerulosclerosis (SRN1), respectively. To investigate the mechanisms by which mutations might cause glomerular protein leak, we analysed NPHS1/NPHS2 genotype/phenotype relationships in 41 non-Finnish CNF patients, four patients with congenital (onset 0 to 3 months) focal segmental glomerulosclerosis and five patients with possible SRN1 (onset 6 months to 2 years). We clarify the range of NPHS1 mutations in CNF, detecting mutation 'hot-spots' within the NPHS1 coding sequence. In addition, we describe a novel discordant CNF phenotype characterized by variable clinical severity, apparently influenced by gender. Moreover, we provide evidence that CNF may be genetically heterogeneous by detection of NPHS2 mutations in some CNF patients in whom NPHS1 mutations were not found. We confirm an overlap in the NPHS1/NPHS2 mutation spectrum with the characterization of a unique di-genic inheritance of NPHS1 and NPHS2 mutations, which results in a 'tri-allelic' hit and appears to modify the phenotype from CNF to one of congenital focal segmental glomerulosclerosis (FSGS). This may result from an epistatic gene interaction, and provides a rare example of multiple allelic hits being able to modify an autosomal recessive disease phenotype in humans. Our findings provide the first evidence for a functional inter-relationship between NPHS1 and NPHS2 in human nephrotic disease, thus underscoring their critical role in the regulation of glomerular filtration. PMID:11854170

  6. Comparison between a serum creatinine-and a cystatin C-based glomerular filtration rate equation in patients receiving amphotericin B.

    PubMed

    Karimzadeh, Iman; Khalili, Hossein

    2016-01-01

    Serum cystatin C (Cys C) has a number of advantages over serum creatinine in the evaluation of kidney function. Apart from Cys C level itself, several formulas have also been introduced in different clinical settings for the estimation of glomerular filtration rate (GFR) based upon serum Cys C level. The aim of the present study was to compare a serum Cys C-based equation with Cockcroft-Gault serum creatinine-based formula, both used in the calculation of GFR, in patients receiving amphotericin B. Fifty four adult patients with no history of acute or chronic kidney injury having been planned to receive conventional amphotericin B for an anticipated duration of at least 1 week for any indication were recruited. At three time points during amphotericin B treatment, including days 0, 7, and 14, serum cystatin C as well as creatinine levels were measured. GFR at the above time points was estimated by both creatinine (Cockcroft-Gault) and serum Cys C based equations. There was significant correlation between creatinine-based and Cys C-based GFR values at days 0 (R = 0.606, P = 0.001) and 7 (R = 0.714, P < 0.001). In contrast to GFR estimated by the Cockcroft-Gault equation, the mean (95 % confidence interval) Cys C-based GFR values at different studied time points were comparable within as well as between patients with and without amphotericin B nephrotoxicity. Our results suggested that the Gentian Cys C-based GFR equation correlated significantly with the Cockcroft-Gault formula at least at the early time period of treatment with amphotericin B. Graphical abstract Comparison between a serum creatinine-and a cystatin C-based glomerular filtration rate equation in patients receiving amphotericin B. PMID:27267989

  7. Knockdown of ApoL1 in Zebrafish Larvae Affects the Glomerular Filtration Barrier and the Expression of Nephrin.

    PubMed

    Kotb, Ahmed M; Simon, Ole; Blumenthal, Antje; Vogelgesang, Silke; Dombrowski, Frank; Amann, Kerstin; Zimmermann, Uwe; Endlich, Karlhans; Endlich, Nicole

    2016-01-01

    APOL1, a secreted high-density lipoprotein, is expressed in different human tissues. Genetic variants of APOL1 are described to be associated with the development of end stage renal diseases in African Americans. In human kidney, APOL1 is mainly expressed in podocytes that are responsible for proper blood filtration. Since mice do not express ApoL1, the zebrafish is an ideal model to study the role of ApoL1. Injection of morpholinos against zApoL1 into zebrafish eggs and larvae, respectively, induces severe edema indicating a leakage of the filtration barrier. This was demonstrated in zApoL1 knockdown larvae by intravascular injection of fluorescently-labeled 10- and 500-kDa dextrans and by clearance of the vitamin D-binding protein from the circulation. Immunohistochemistry and RT-PCR revealed the reduction of nephrin, a podocyte-specific protein essential for blood filtration. Coinjection of human nephrin mRNA rescued the zApoL1 knockdown induced phenotype. Reduced APOL1 and nephrin levels were also found in biopsies of patients suffering from end stage renal diseases. Our results demonstrate that zApoL1 is essential for proper blood filtration in the zebrafish glomerulus and that zApoL1 affects the expression of nephrin. PMID:27138898

  8. Knockdown of ApoL1 in Zebrafish Larvae Affects the Glomerular Filtration Barrier and the Expression of Nephrin

    PubMed Central

    Kotb, Ahmed M.; Simon, Ole; Blumenthal, Antje; Vogelgesang, Silke; Dombrowski, Frank; Amann, Kerstin; Zimmermann, Uwe; Endlich, Karlhans; Endlich, Nicole

    2016-01-01

    APOL1, a secreted high-density lipoprotein, is expressed in different human tissues. Genetic variants of APOL1 are described to be associated with the development of end stage renal diseases in African Americans. In human kidney, APOL1 is mainly expressed in podocytes that are responsible for proper blood filtration. Since mice do not express ApoL1, the zebrafish is an ideal model to study the role of ApoL1. Injection of morpholinos against zApoL1 into zebrafish eggs and larvae, respectively, induces severe edema indicating a leakage of the filtration barrier. This was demonstrated in zApoL1 knockdown larvae by intravascular injection of fluorescently-labeled 10- and 500-kDa dextrans and by clearance of the vitamin D-binding protein from the circulation. Immunohistochemistry and RT-PCR revealed the reduction of nephrin, a podocyte-specific protein essential for blood filtration. Coinjection of human nephrin mRNA rescued the zApoL1 knockdown induced phenotype. Reduced APOL1 and nephrin levels were also found in biopsies of patients suffering from end stage renal diseases. Our results demonstrate that zApoL1 is essential for proper blood filtration in the zebrafish glomerulus and that zApoL1 affects the expression of nephrin. PMID:27138898

  9. Associations of Perfluoroalkyl Substances (PFAS) with Lower Birth Weight: An Evaluation of Potential Confounding by Glomerular Filtration Rate Using a Physiologically Based Pharmacokinetic Model (PBPK)

    PubMed Central

    Loccisano, Anne E.; Morken, Nils-Halvdan; Yoon, Miyoung; Wu, Huali; McDougall, Robin; Maisonet, Mildred; Marcus, Michele; Kishi, Reiko; Miyashita, Chihiro; Chen, Mei-Huei; Hsieh, Wu-Shiun; Andersen, Melvin E.; Clewell, Harvey J.; Longnecker, Matthew P.

    2015-01-01

    Background Prenatal exposure to perfluoroalkyl substances (PFAS) has been associated with lower birth weight in epidemiologic studies. This association could be attributable to glomerular filtration rate (GFR), which is related to PFAS concentration and birth weight. Objectives We used a physiologically based pharmacokinetic (PBPK) model of pregnancy to assess how much of the PFAS–birth weight association observed in epidemiologic studies might be attributable to GFR. Methods We modified a PBPK model to reflect the association of GFR with birth weight (estimated from three studies of GFR and birth weight) and used it to simulate PFAS concentrations in maternal and cord plasma. The model was run 250,000 times, with variation in parameters, to simulate a population. Simulated data were analyzed to evaluate the association between PFAS levels and birth weight due to GFR. We compared simulated estimates with those from a meta-analysis of epidemiologic data. Results The reduction in birth weight for each 1-ng/mL increase in simulated cord plasma for perfluorooctane sulfonate (PFOS) was 2.72 g (95% CI: –3.40, –2.04), and for perfluorooctanoic acid (PFOA) was 7.13 g (95% CI: –8.46, –5.80); results based on maternal plasma at term were similar. Results were sensitive to variations in PFAS level distributions and the strength of the GFR–birth weight association. In comparison, our meta-analysis of epidemiologic studies suggested that each 1-ng/mL increase in prenatal PFOS and PFOA levels was associated with 5.00 g (95% CI: –21.66, –7.78) and 14.72 g (95% CI: –8.92, –1.09) reductions in birth weight, respectively. Conclusion Results of our simulations suggest that a substantial proportion of the association between prenatal PFAS and birth weight may be attributable to confounding by GFR and that confounding by GFR may be more important in studies with sample collection later in pregnancy. Citation Verner MA, Loccisano AE, Morken NH, Yoon M, Wu H, Mc

  10. The cystatin C/creatinine ratio, a marker of glomerular filtration quality: associated factors, reference intervals, and prediction of morbidity and mortality in healthy seniors.

    PubMed

    Purde, Mette-Triin; Nock, Stefan; Risch, Lorenz; Medina Escobar, Pedro; Grebhardt, Chris; Nydegger, Urs E; Stanga, Zeno; Risch, Martin

    2016-03-01

    The ratio of cystatin C (cysC) to creatinine (crea) is regarded as a marker of glomerular filtration quality associated with cardiovascular morbidities. We sought to determine reference intervals for serum cysC-crea ratio in seniors. Furthermore, we sought to determine whether other low-molecular weight molecules exhibit a similar behavior in individuals with altered glomerular filtration quality. Finally, we investigated associations with adverse outcomes. A total of 1382 subjectively healthy Swiss volunteers aged 60 years or older were enrolled in the study. Reference intervals were calculated according to Clinical & Laboratory Standards Institute (CLSI) guideline EP28-A3c. After a baseline exam, a 4-year follow-up survey recorded information about overall morbidity and mortality. The cysC-crea ratio (mean 0.0124 ± 0.0026 mg/μmol) was significantly higher in women and increased progressively with age. Other associated factors were hemoglobin A1c, mean arterial pressure, and C-reactive protein (P < 0.05 for all). Participants exhibiting shrunken pore syndrome had significantly higher ratios of 3.5-66.5 kDa molecules (brain natriuretic peptide, parathyroid hormone, β2-microglobulin, cystatin C, retinol-binding protein, thyroid-stimulating hormone, α1-acid glycoprotein, lipase, amylase, prealbumin, and albumin) and creatinine. There was no such difference in the ratios of very low-molecular weight molecules (urea, uric acid) to creatinine or in the ratios of molecules larger than 66.5 kDa (transferrin, haptoglobin) to creatinine. The cysC-crea ratio was significantly predictive of mortality and subjective overall morbidity at follow-up in logistic regression models adjusting for several factors. The cysC-crea ratio exhibits age- and sex-specific reference intervals in seniors. In conclusion, the cysC-crea ratio may indicate the relative retention of biologically active low-molecular weight compounds and can independently predict the risk for overall

  11. Results of the first-in-human clinical trial for MB-102, a novel fluorescent tracer agent for real-time measurement of glomerular filtration rate

    NASA Astrophysics Data System (ADS)

    Dorshow, Richard B.; Debreczeny, Martin P.; Dowling, Thomas C.

    2015-03-01

    The fluorescent tracer agent 2,5-bis[N-(1-carboxy-2-hydroxy)]carbamoyl-3,6-diaminopyrazine, designated MB-102, has been developed with properties and attributes necessary for use as a direct measure of glomerular filtration rate (GFR). Comparison to known standard exogenous GFR agents in animal models has demonstrated an excellent correlation. A clinical trial to demonstrate this same correlation in humans is in progress. This clinical trial is the first in a series of trials necessary to obtain regulatory clearance from the FDA. We report herein the comparison of plasma pharmacokinetics between MB-102 and the known standard exogenous GFR agent Iohexol in healthy subjects with normal renal function. Post simultaneous administration of both agents, blood samples over a period of 12 hours were collected from each subject to assess pharmacokinetic parameters including GFR. Urine samples were collected over this same period to assess percent injected dose recovered in the urine. Results indicate MB-102 is a GFR agent in humans from the comparison to the standard agent.

  12. Chromatographic estimation of iothalamate and p-aminohippuric acid to measure glomerular filtration rate and effective renal plasma flow in humans.

    PubMed

    Agarwal, R

    1998-01-23

    Iothalamate (IOT) clearance and p-aminohippuric acid (PAH) clearance are used for estimation of glomerular filtration rate (GFR) and effective renal plasma flow (ERPF). A simple and rapid method is described for simultaneous determination of IOT and PAH in the same chromatogram in the serum and urine of humans. The mobile phase consisted of methanol-50 mM sodium monobasic phosphate with 0.5 mM tetrabutyl ammonium hydrogen sulfate (18:82, v/v), pumped at a rate of 0.8 ml/min on a C18 reversed-phase column. Samples of serum and urine were deproteinized with two volumes of acetonitrile containing the internal standard, p-aminobenzoic acid (PABA). The UV detector was set at 254 nm and peak height ratios of PAH or IOT to PABA were calculated with an integrator. Precision and accuracy were within 15% for both PAH and IOT. The recovery of PAH in urine and serum were 94% and 91%, respectively. For IOT the corresponding recoveries were 93% and 92%, respectively. This method clearly distinguishes acetyl-PAH from PAH and has been validated in healthy volunteers. PMID:9498664

  13. Flow Mediated Dilatation Is Reduced with the Progressive Stages of Glomerular Filtration Rate and Albuminuria in Type 2 Diabetic Patients without Coronary Heart Disease

    PubMed Central

    Ito, Hiroyuki; Nakashima, Mina; Meguro, Kentaro; Furukawa, Haruki; Yamashita, Hitomi; Takaki, Akifusa; Yukawa, Chizuko; Omoto, Takashi; Shinozaki, Masahiro; Nishio, Shinya; Abe, Mariko; Antoku, Shinichi; Mifune, Mizuo; Togane, Michiko

    2015-01-01

    We aimed to clarify the usefulness of measuring the flow mediated dilatation (FMD) in patients with type 2 diabetes mellitus without and with coronary heart disease (CHD). The FMD was measured in 480 patients with type 2 diabetes and in 240 nondiabetic subjects. The FMD was significantly lower in the subjects with CHD (n = 145, 5.4 ± 3.2%) than in those without CHD (n = 95, 6.9 ± 3.5%) among the nondiabetic subjects. The FMD was also lower in the subjects both with CHD (n = 161, 5.6 ± 2.8%) and without CHD (n = 319, 6.1 ± 3.3%) among the patients with diabetes compared to those without both diabetes and CHD. The FMD showed a significant positive correlation with the estimated glomerular filtration rate (eGFR) in the diabetic patients without CHD, while there was no significant association in those with CHD. The FMD was significantly lower with the progressive stages of the GFR or albuminuria in the patients without CHD among those with diabetes, although the FMD was not different in those with CHD. In conclusion, the FMD is considered to be useful for the detection of atherosclerosis in patients with type 2 diabetes, even if overt macroangiopathy is not diagnosed. PMID:26064988

  14. Intermediate Volume on Computed Tomography Imaging Defines a Fibrotic Compartment that Predicts Glomerular Filtration Rate Decline in Autosomal Dominant Polycystic Kidney Disease Patients

    PubMed Central

    Caroli, Anna; Antiga, Luca; Conti, Sara; Sonzogni, Aurelio; Fasolini, Giorgio; Ondei, Patrizia; Perico, Norberto; Remuzzi, Giuseppe; Remuzzi, Andrea

    2011-01-01

    Total kidney and cyst volumes have been used to quantify disease progression in autosomal dominant polycystic kidney disease (ADPKD), but a causal relationship with progression to renal failure has not been demonstrated. Advanced image processing recently allowed to quantify extracystic tissue, and to identify an additional tissue component named “intermediate,” appearing hypoenhanced on contrast-enhanced computed tomography (CT). The aim of this study is to provide a histological characterization of intermediate volume, investigate its relation with renal function, and provide preliminary evidence of its role in long-term prediction of functional loss. Three ADPKD patients underwent contrast-enhanced CT scans before nephrectomy. Histological samples of intermediate volume were drawn from the excised kidneys, and stained with hematoxylin and eosin and with saturated picrosirius solution for histological analysis. Intermediate volume showed major structural changes, characterized by tubular dilation and atrophy, microcysts, inflammatory cell infiltrate, vascular sclerosis, and extended peritubular interstitial fibrosis. A significant correlation (r = −0.69, P < 0.001) between relative intermediate volume and baseline renal function was found in 21 ADPKD patients. Long-term prediction of renal functional loss was investigated in an independent cohort of 13 ADPKD patients, followed for 3 to 8 years. Intermediate volume, but not total kidney or cyst volume, significantly correlated with glomerular filtration rate decline (r = −0.79, P < 0.005). These findings suggest that intermediate volume may represent a suitable surrogate marker of ADPKD progression and a novel therapeutic target. PMID:21683674

  15. Impact of urine concentration adjustment method on associations between urine metals and estimated glomerular filtration rates (eGFR) in adolescents☆

    PubMed Central

    Weaver, Virginia M.; Vargas, Gonzalo García; Silbergeld, Ellen K.; Rothenberg, Stephen J.; Fadrowski, Jeffrey J.; Rubio-Andrade, Marisela; Parsons, Patrick J.; Steuerwald, Amy J.; Navas-Acien, Ana; Guallar, Eliseo

    2014-01-01

    Positive associations between urine toxicant levels and measures of glomerular filtration rate (GFR) have been reported recently in a range of populations. The explanation for these associations, in a direction opposite that of traditional nephrotoxicity, is uncertain. Variation in associations by urine concentration adjustment approach has also been observed. Associations of urine cadmium, thallium and uranium in models of serum creatinine- and cystatin-C-based estimated GFR (eGFR) were examined using multiple linear regression in a cross-sectional study of adolescents residing near a lead smelter complex. Urine concentration adjustment approaches compared included urine creatinine, urine osmolality and no adjustment. Median age, blood lead and urine cadmium, thallium and uranium were 13.9 years, 4.0 μg/dL, 0.22, 0.27 and 0.04 g/g creatinine, respectively, in 512 adolescents. Urine cadmium and thallium were positively associated with serum creatinine-based eGFR only when urine creatinine was used to adjust for urine concentration (β coefficient=3.1 mL/min/1.73 m2; 95% confidence interval=1.4, 4.8 per each doubling of urine cadmium). Weaker positive associations, also only with urine creatinine adjustment, were observed between these metals and serum cystatin-C-based eGFR and between urine uranium and serum creatinine-based eGFR. Additional research using non-creatinine-based methods of adjustment for urine concentration is necessary. PMID:24815335

  16. The impact of serum uric acid on the natural history of glomerular filtration rate: a retrospective study in the general population

    PubMed Central

    Xu, Ying; Liu, Xiang; Sun, Xiaohe

    2016-01-01

    Serum uric acid (SUA) level has been proposed to have important connections with chronic kidney disease (CKD), while the impact of SUA level on the natural history of glomerular filtration rate (GFR) decline remains unknown. The present study aims to study the association of the SUA level with the GFR decline in a general population. Two thousand, seven hundred and eighty-nine subjects who visited the Health Checkup Clinic both at 2008 and 2013 were identified. A significant inverse correlation was observed between change in SUA from 2008–2013 (ΔSUA) and change in eGFR (ΔeGFR) during the same period. Multivariate regression analysis of ΔeGFR indicated that the increase in SUA over time were a negative predictor of the change in eGFR. Our result indicates that the decline of eGFR over years is larger in subjects with an increased SUA level, which helps to underline the importance of SUA level management in the context of kidney function preservation. PMID:27069799

  17. Use of gadolinium diethylene triamine penta-acetic acid, as measured by ELISA, in the determination of glomerular filtration rates in cats.

    PubMed

    Sox, Erika M; Chiotti, Ruthanne; Goldstein, Richard E

    2010-10-01

    The goal of this study was to evaluate a commercially available assay for gadolinium diethylene triamine penta-acetic acid (Gd-DTPA) for use in estimating glomerular filtration rate (GFR) in cats (Gd-DTPA GFR) with a wide range of GFRs. Eighteen adult cats (11 healthy and seven with chronic kidney disease) were included. Plasma concentrations of Gd-DTPA following intravenous injection were measured with an ELISA kit (FIT-GFR). Results for Gd-DTPA GFR were compared with simultaneously obtained values for plasma clearance of iohexol (iohexol GFR), plasma blood urea nitrogen (BUN) and creatinine concentrations. A negative correlation existed between iohexol GFR and plasma concentrations of BUN and creatinine. A positive correlation existed between Gd-DTPA GFR and iohexol GFR. There was no correlation between Gd-DTPA GFR and plasma concentrations of BUN and creatinine. In this study plasma clearance of Gd-DTPA assayed by FIT-GFR did not appear to provide a sufficiently accurate estimation of GFR in cats when compared with plasma clearance of iohexol, and plasma concentrations of BUN and creatinine. PMID:20724186

  18. A Comparative Study of Sonographic Grading of Renal Parenchymal Changes and Estimated Glomerular Filtration Rate (eGFR) using Modified Diet in Renal Disease Formula

    PubMed Central

    Shivalli, Siddharudha; Pai, B.H. Santhosh; Acharya, Koteshwara Devadasa; Gopalakrishnan, Ravichandra; Srikanth, Vivek; Reddy, Vishwanath; Haris, Arafat

    2016-01-01

    Introduction The sonographic findings are of help in evaluating the nephrological diseases. Glomerular filtration rate is another parameter for assessing the reserved renal function and an indicator of prognosis. In clinical practice GFR estimation (eGFR) is done by using a mathematical formula. In our study, we compared the sonographic grading of renal parenchymal changes with eGFR calculated using Modified Diet in Renal Diseases formula based on serum creatinine, age, gender and ethnicity. Aim To evaluate the relevance of sonographic grading of renal parenchymal changes in assessing the severity of the renal disease and comparing it to the eGFR calculated using MDRD formula based on the age, gender and serum creatinine value of the patient. Materials and Methods The adult patients with suspected kidney disease referred for sonography of abdomen were our study participants. As per our study design following strict inclusion and exclusion criteria, patients were selected as study participants and for each of the patient’s renal parenchymal status, serum creatinine, age, gender and ethnicity were documented. Results A total of 70 patients were our study participants, out of which 67.1% were males and 32.9% were females. Our study showed a linear correlation between sonographic grading of renal parenchymal changes with eGFR. Conclusion We conclude that by evaluating the kidneys with sonography and calculating eGFR using MDRD formula the renal status will be more accurately interpreted. PMID:27042555

  19. Glomerular filtration rate in adults estimated from 123iodine-hippuran and 99mtechnetium-diethylenetriaminepenta-acetic acid gamma camera renography.

    PubMed

    Carlsen, O; Nathan, E

    1988-08-01

    In a retrospective study a close relationship was found between the rate constant for renal clearance of the radioactive indicator (lambda pk) and the glomerular filtration rate (GFR) measured by 51Cr-EDTA plasma clearance. The material comprised eighteen adult subjects submitted to 123I-hippuran gamma camera renography (IHGR) and twenty-two adult subjects to 99mTc-DTPA gamma camera renography (TDGR). The rate constant was calculated from a bi-exponential decomposition of the activity-time curve recorded within a small region of interest over the left ventricle. The total cleared renal fraction (TCRF) of the cardiac output with respect to the radioactive indicator has previously been shown to be closely related to GFR. A pooled estimate of GFR (GFRp) was calculated from the stochastically independent estimates of GFR based on lambda pk and TCRF. The comparison of GFRp with measured GFR was satisfactory and yielded substantially smaller standard deviations (SD) of GFRp than estimates based on lambda pk and TCRF separately. The standard deviations of GFRp were about 7 and 12 ml/min/1.73 m2 in IHGR for GFR equal to 50 and 100 ml/min/1.73 m2, respectively. The corresponding SD in TDGR were about 7 and 11 ml/min/1.73 m2. These standard deviations are sufficiently small for many clinical purposes and the method requires no blood samples or urine collections. PMID:3044675

  20. Bone Density Is Directly Associated With Glomerular Filtration and Metabolic Acidosis but Do Not Predict Fragility Fractures in Men With Moderate Chronic Kidney Disease.

    PubMed

    Lima, Guilherme Alcantara Cunha; de Paula Paranhos-Neto, Francisco; Silva, Luciana Colonese; de Mendonça, Laura Maria Carvalho; Delgado, Alvimar Gonçalves; Leite, Maurilo; Gomes, Carlos Perez; Farias, Maria Lucia Fleiuss

    2016-01-01

    Hyperparathyroidism, vitamin D deficiency, increased fibroblast growth factor-23 (FGF-23), and metabolic acidosis promote bone fragility in chronic kidney disease (CKD). Although useful in predicting fracture risk in the general population, the role of dual-energy X-ray absorptiometry (DXA) in CKD remains uncertain. This cross-sectional study included 51 men aged 50-75 yr with moderate CKD. The stage 4 CKD patients had higher levels of parathyroid hormone (p<0.001), FGF-23 (p=0.029), and lowest 25-hydroxyvitamin D (p=0.016), bicarbonate (p<0.001), total femur (p=0.003), and femoral neck (p=0.011) T-scores compared with stage 3 CKD patients. Total femur and femoral neck T-scores were directly correlated with serum bicarbonate (p=0.003, r=0.447 and p=0.005, r=0.427, respectively) and estimated glomerular filtration rate (p=0.024, r=0.325 and p=0.003, r=0.313, respectively) but were not significantly associated with parathyroid hormone, 25-hydroxyvitamin D, or FGF-23. Only 3.9% of the participants had osteoporosis on DXA scan, whereas 31.4% reported a low-impact fracture. Our data point to a pivotal role of metabolic acidosis for bone impairment and to the inadequacy of DXA to evaluate bone fragility in CKD patients. PMID:24709549

  1. Tamm-Horsfall Protein Regulates Circulating and Renal Cytokines by Affecting Glomerular Filtration Rate and Acting as a Urinary Cytokine Trap*

    PubMed Central

    Liu, Yan; El-Achkar, Tarek M.; Wu, Xue-Ru

    2012-01-01

    Although few organ systems play a more important role than the kidneys in cytokine catabolism, the mechanism(s) regulating this pivotal physiological function and how its deficiency affects systemic cytokine homeostasis remain unclear. Here we show that elimination of Tamm-Horsfall protein (THP) expression from mouse kidneys caused a marked elevation of circulating IFN-γ, IL1α, TNF-α, IL6, CXCL1, and IL13. Accompanying this were enlarged spleens with prominent white-pulp macrophage infiltration. Lipopolysaccharide (LPS) exacerbated the increase of serum cytokines without a corresponding increase in their urinary excretion in THP knock-out (KO) mice. This, along with the rise of serum cystatin C and the reduced inulin and creatinine clearance from the circulation, suggested that diminished glomerular filtration may contribute to reduced cytokine clearance in THP KO mice both at the baseline and under stress. Unlike wild-type mice where renal and urinary cytokines formed specific in vivo complexes with THP, this “trapping” effect was absent in THP KO mice, thus explaining why cytokine signaling pathways were activated in renal epithelial cells in such mice. Our study provides new evidence implicating an important role of THP in influencing cytokine clearance and acting as a decoy receptor for urinary cytokines. Based on these and other data, we present a unifying model that underscores the role of THP as a major regulator of renal and systemic immunity. PMID:22451664

  2. Initial formal toxicity evaluation of APC-2, a novel fluorescent tracer agent for real-time measurement of glomerular filtration rate in preparation for a first-in-man clinical trial

    NASA Astrophysics Data System (ADS)

    Bugaj, Joseph E.; Dorshow, Richard B.

    2014-03-01

    The fluorescent tracer agent 2,5-bis[N-(1-carboxy-2-hydroxy)]carbamoyl-3,6-diaminopyrazine, designated APC-2, has been developed with properties and attributes necessary for use as a direct measure of glomerular filtration rate (GFR). Comparison to known standard exogenous GFR agents in animal models has demonstrated an excellent correlation. A clinical trial to demonstrate this same correlation in humans is in preparation. A battery of formal toxicity tests necessary for regulatory clearance to proceed with a clinical trial has been recently completed on this new fluorescent tracer agent. These include single dose toxicity studies in rats and dogs to determine overall toxicity and toxicokinetics of the compound. Blood compatibility, mutation assay, chromosomal aberration assay, and several other assays were also completed. Toxicity assessments were based on mortality, clinical signs, body weight, food consumption and anatomical pathology. Blood samples were collected to assess pharmacokinetic parameters including half-life, area under the curve, and clearance. Urine samples were collected to assess distribution. Doses of up to 200-300 times the estimated human dose were administered. No test-article related effects were noted on body weight, food consumption, ophthalmic observations and no abnormal pathology was seen in either macroscopic or microscopic evaluations of any organs or tissues. All animals survived to scheduled sacrifice. Transient discoloration of skin and urine was noted at the higher dose levels in both species as expected from a highly fluorescent compound and was not considered pathological. Thus initial toxicology studies of this new fluorescent tracer agent APC-2 have resulted in no demonstrable pathological test article concerns.

  3. Differential effect of T-type voltage-gated Ca2+ channel disruption on renal plasma flow and glomerular filtration rate in vivo.

    PubMed

    Thuesen, Anne D; Andersen, Henrik; Cardel, Majken; Toft, Anja; Walter, Steen; Marcussen, Niels; Jensen, Boye L; Bie, Peter; Hansen, Pernille B L

    2014-08-15

    Voltage-gated Ca(2+) (Cav) channels play an essential role in the regulation of renal blood flow and glomerular filtration rate (GFR). Because T-type Cav channels are differentially expressed in pre- and postglomerular vessels, it was hypothesized that they impact renal blood flow and GFR differentially. The question was addressed with the use of two T-type Cav knockout (Cav3.1(-/-) and Cav3.2(-/-)) mouse strains. Continuous recordings of blood pressure and heart rate, para-aminohippurate clearance (renal plasma flow), and inulin clearance (GFR) were performed in conscious, chronically catheterized, wild-type (WT) and Cav3.1(-/-) and Cav3.2(-/-) mice. The contractility of afferent and efferent arterioles was determined in isolated perfused blood vessels. Efferent arterioles from Cav3.2(-/-) mice constricted significantly more in response to a depolarization compared with WT mice. GFR was increased in Cav3.2(-/-) mice with no significant changes in renal plasma flow, heart rate, and blood pressure. Cav3.1(-/-) mice had a higher renal plasma flow compared with WT mice, whereas GFR was indistinguishable from WT mice. No difference in the concentration response to K(+) was observed in isolated afferent and efferent arterioles from Cav3.1(-/-) mice compared with WT mice. Heart rate was significantly lower in Cav3.1(-/-) mice compared with WT mice with no difference in blood pressure. T-type antagonists significantly inhibited the constriction of human intrarenal arteries in response to a small depolarization. In conclusion, Cav3.2 channels support dilatation of efferent arterioles and affect GFR, whereas Cav3.1 channels in vivo contribute to renal vascular resistance. It is suggested that endothelial and nerve localization of Cav3.2 and Cav3.1, respectively, may account for the observed effects. PMID:24966091

  4. Impact of urine concentration adjustment method on associations between urine metals and estimated glomerular filtration rates (eGFR) in adolescents

    SciTech Connect

    Weaver, Virginia M.; Vargas, Gonzalo García; Silbergeld, Ellen K.; Rothenberg, Stephen J.; Fadrowski, Jeffrey J.; Rubio-Andrade, Marisela; Parsons, Patrick J.; Steuerwald, Amy J.; and others

    2014-07-15

    Positive associations between urine toxicant levels and measures of glomerular filtration rate (GFR) have been reported recently in a range of populations. The explanation for these associations, in a direction opposite that of traditional nephrotoxicity, is uncertain. Variation in associations by urine concentration adjustment approach has also been observed. Associations of urine cadmium, thallium and uranium in models of serum creatinine- and cystatin-C-based estimated GFR (eGFR) were examined using multiple linear regression in a cross-sectional study of adolescents residing near a lead smelter complex. Urine concentration adjustment approaches compared included urine creatinine, urine osmolality and no adjustment. Median age, blood lead and urine cadmium, thallium and uranium were 13.9 years, 4.0 μg/dL, 0.22, 0.27 and 0.04 g/g creatinine, respectively, in 512 adolescents. Urine cadmium and thallium were positively associated with serum creatinine-based eGFR only when urine creatinine was used to adjust for urine concentration (β coefficient=3.1 mL/min/1.73 m{sup 2}; 95% confidence interval=1.4, 4.8 per each doubling of urine cadmium). Weaker positive associations, also only with urine creatinine adjustment, were observed between these metals and serum cystatin-C-based eGFR and between urine uranium and serum creatinine-based eGFR. Additional research using non-creatinine-based methods of adjustment for urine concentration is necessary. - Highlights: • Positive associations between urine metals and creatinine-based eGFR are unexpected. • Optimal approach to urine concentration adjustment for urine biomarkers uncertain. • We compared urine concentration adjustment methods. • Positive associations observed only with urine creatinine adjustment. • Additional research using non-creatinine-based methods of adjustment needed.

  5. Areca Nut Chewing and an Impaired Estimated Glomerular Filtration Rate as Significant Risk Factors for Non-Muscle-Invasive Bladder Cancer Recurrence

    PubMed Central

    Cao, Jian; Xu, Ran; Zhao, Xiaokun; Zhong, Zhaohui; Zhang, Lei; Zhu, Xuan; Wu, Shuiqing; Ai, Kai

    2016-01-01

    The present study sought to investigate the predictive value of preoperative clinicopathological variables, with a special focus on areca nut chewing, on disease recurrence and progression in patients with non-muscle-invasive bladder cancer (NMIBC). Data from 242 patients diagnosed with NMIBC between 2008 and 2013 were analyzed retrospectively. Fifteen clinicopathological variables were analyzed to evaluate their prognostic value. During a mean observation period of 21 months, disease recurrence occurred in 140 patients (57.9%). On multivariate analysis, heavy-areca nut chewing (HR = 2.18, 95% CI: 1.37–3.47), current smoking (HR = 3.09, 95% CI: 1.99–4.80), moderately impaired estimated glomerular filtration rate (eGFR) (HR = 1.76, 95% CI: 1.09–2.83), severely impaired eGFR (HR = 3.32, 95% CI: 1.70–6.48) and tumor grade (HR = 1.94, 95% CI: 1.36–2.77) were independent factors for recurrence, based on which a risk factor model was developed to stratify patients into high, medium and low risk groups. In conclusion, our study suggests that in addition to quitting smoking, quitting areca nut chewing may also reduce the risk of first recurrence in NMBIC patients, monitoring and preserving their renal function may be beneficial as well. Further prospective studies are needed to verify the prognostic significance of these factors and the risk stratification model in this population. PMID:27385379

  6. Proteinuria and Reduced Estimated Glomerular Filtration Rate Independently Predict Risk for Acute Myocardial Infarction: Findings from a Population-Based Study in Keelung, Taiwan

    PubMed Central

    Chang, Shu-Hsuan; Tsai, Chia-Ti; Yen, Amy Ming-Fang; Lei, Meng-Huan; Chen, Hsiu-Hsi; Tseng, Chuen-Den

    2015-01-01

    Background The aim of this study was to evaluate the independent roles of proteinuria and reduced estimated glomerular filtration rate (GFR) in the development of acute myocardial infarction in a northern Taiwanese population. Methods We conducted a community-based prospective cohort study in Keelung, the northernmost county of Taiwan. A total of 63,129 subjects (63% women) ≥ 20 years of age who had no history of coronary heart disease were recruited and followed-up. Univariate and multivariate proportional hazards regression analysis was performed to assess the association between proteinuria and estimated GFR and the risk of acute myocardial infarction. Results There were 305 new cases of acute myocardial infarction (114 women and 191 men) documented during a four-year follow-up period. After adjustment of potential confounding covariates, heavier proteinuria (dipstick urinalysis reading 3+) and estimated GFR of less than 60 ml/min/1.73 m2 independently predicted increased risk of developing acute myocardial infarction. The adjusted hazard ratio (aHR) of heavier proteinuria for occurrence of acute myocardial infarction was 1.85 [95% confidence intervals (CI), 1.17-2.91, p < 0.01] (vs. the reference group: negative dipstick proteinuria). The aHR of estimated GFR of 30-59 ml/min/1.73 m2 for occurrence of acute myocardial infarction was 2.4 (95% CI, 1.31-4.38, p < 0.01) (vs. the reference group: estimated GFR ≥ 90 ml/ min/1.73 m2), and that of estimated GFR of 15-29 ml/min/1.73 m2 was 5.26 (95% CI, 2.26-12.26, p < 0.01). Conclusions We demonstrated that both heavier proteinuria and lower estimated GFR are significant independent predictors of developing future acute myocardial infarction in a northern Taiwanese population. PMID:27122856

  7. Glomerular filtration rate estimated by creatinine, cystatin C, or both markers and the risk of clinical events in HIV-infected individuals

    PubMed Central

    Lucas, Gregory M.; Cozzi-Lepri, Alessandro; Wyatt, Christina M.; Post, Frank A.; Bormann, Alison M.; Crum-Cianflone, Nancy F.; Ross, Michael J.

    2013-01-01

    Background The accuracy and precision of glomerular filtration rate (GFR) estimating equations based on plasma creatinine (GFRcr), cystatin C (GFRcys), and the combination of these markers (GFRcr-cys) has recently been assessed in HIV-infected individuals. Methods We compared the associations of baseline GFRcr, GFRcys, and GFRcr-cys (using the CKD-EPI equations) with mortality, cardiovascular events (CVE), and opportunistic diseases (OD) in the Strategies for the Management of Antiretroviral Therapy (SMART) study. We used Cox proportional hazards models to estimate unadjusted and adjusted hazard ratios per standard deviation (SD) change in GFR. Results 4,614 subjects from the SMART trial with available baseline creatinine and cystatin C data were included in this analysis. Of these, 99 died, 111 had a CVE and 121 had an OD. GFRcys was weakly to moderately correlated with HIV RNA, CD4 cell count, high sensitivity C-reactive protein, interleukin-6, and D-dimer, while GFRcr had little or no correlation with these factors. GFRcys had the strongest associations with the three clinical outcomes, followed closely by GFRcr-cys, with GFRcr having the weakest associations with clinical outcomes. In a model adjusting for demographics, cardiovascular risk factors, HIV-related factors, and inflammation markers, a 1-SD lower GFRcys was associated with a 55% (95% confidence interval [CI], 27% -90%) increased risk of mortality, a 21% (95% CI, 0% -47%) increased risk of CVE, and a 22% (95% CI, 0% -48%) increased risk of OD. Conclusions Of the three CKD-EPI GFR equations, GFRcys had the strongest associations with mortality, CVE, and OD. PMID:24024499

  8. Long-Term Follow-Up of Proteinuria and Estimated Glomerular Filtration Rate in HIV-Infected Patients with Tubular Proteinuria

    PubMed Central

    Peyriere, Hélène; Cournil, Amandine; Casanova, Marie-Laure; Badiou, Stéphanie; Cristol, Jean-Paul; Reynes, Jacques

    2015-01-01

    Objective The objective of this prospective observational study was to describe the evolution of tubular proteinuria detected in HIV-infected patients, and to evaluate the impact of tenofovir disoproxil fumarate (TDF) discontinuation. Methods Proteinuria and estimated glomerular filtration rate (eGFR) were followed during a median duration of 32 months, in 81 HIV-infected patients with tubular proteinuria and eGFR ≥ 60 ml/min/1.73 m2 (determined using the Chronic Kidney Disease Epidemiology (CKD-EPI) Collaboration equation). Tubular proteinuria was defined by urine protein to creatinine ratio (uPCR) ≥200 mg/g and albumin to protein ratio (uAPR) <0.4. Results Twenty per cent of patients had persistence of tubular proteinuria: TDF continuation was the main factor associated with this persistence [OR 9.0; 95%CI: 1.9–41.4; p = 0.01]. Among the 23 patients who discontinued TDF, uPCR returned below the threshold of 200 mg/g in 11 patients. Overall, eGFR decreased with a mean rate of decline of 3.8 ml/min/1.73m2/year. The decline in eGFR was lesser after discontinuation of TDF (5.8 ml/min/1.73m2/year during TDF exposure versus 3 ml/min/1.73m2/year after TDF discontinuation; p = 0.01). Conclusions The continuation of TDF was the main factor associated with the persistence of proteinuria. Moreover, proteinuria was normalized in only half of the patients who discontinued TDF. The clinical significance of TDF-related low level of proteinuria as a factor associated with renal disease progression and bone loss remains poorly understood. PMID:26571117

  9. Evaluation of creatinine-based and cystatin C-based equations for estimation of glomerular filtration rate in type 1 diabetic patients.

    PubMed

    Domingueti, Caroline Pereira; Fóscolo, Rodrigo Bastos; Simões E Silva, Ana Cristina; Dusse, Luci Maria S; Reis, Janice Sepúlveda; Carvalho, Maria das Graças; Fernandes, Ana Paula; Gomes, Karina Braga

    2016-04-01

    Objective Several formulas based in different biomarkers may be used to estimate glomerular filtration rate (GRF). However, all of them have some limitations, and it is very important to evaluate their performances in different groups of patients. Therefore, we compared GFR, as estimated by creatinine-based and cystatin C-based equations, according to albuminuria, in type 1 diabetes (T1DM), in an observational case-control study. Subjects and methods T1DM patients were classified according to albuminuria: normoalbuminuric (n = 63), microalbuminuric (n = 30), macroalbuminuric (n = 32). GFR was calculated using creatinine-based and cystatin C-based (aMDRD, CKD-EPIcr, CKD-EPIcys, MacIsaac, Tan and CKD-EPIcrcys) equations. Spearman Correlation was used to evaluate the correlation of GFR estimated by the formulas with albuminuria. ROC curves were constructed to compare AUCs of GFR estimated by equations, in reference to macroalbuminuria. Sensibility, specificity and accuracy were calculated for a cut-off < 60 mL/min/1.73 m2. Results GFR estimated by creatinine-based and cystatin C-based equations significantly differed among normoalbuminuric, microalbuminuric and macroalbuminuric patients. Spearman correlation and AUCs of GFR estimated by creatinine-based and cystatin C-based formulas were very similar to each other, though cystatin C-based equations presented better correlation with albuminuria and higher AUCs than the creatinine-based ones, and the best accuracy to detect macroalbuminuric patients. Conclusion Although GFR estimated by all creatinine-based and cystatin C-based equations permitted the differentiation between T1DM patients, according to albuminuria, cystatin C-based equations presented best accuracy to detect macroalbuminuria in T1DM patients and should be considered in the clinical routine in order to increase the possibility of early diagnostic of chronic renal disease. PMID:27191046

  10. Polymorphisms in the Non-Muscle Myosin Heavy Chain Gene (MYH9) Are Associated with Lower Glomerular Filtration Rate in Mixed Ancestry Diabetic Subjects from South Africa

    PubMed Central

    Matsha, Tandi Edith; Masconi, Katya; Yako, Yandiswa Yolanda; Hassan, Mogamat Shafick; Macharia, Muiriri; Erasmus, Rajiv Timothy; Kengne, Andre Pascal

    2012-01-01

    Objective Though single nucleotide polymorphisms (SNPs) in the non-muscle myosin gene (MYH9) have been reported to explain most of the excess risk of nondiabetic chronic kidney disease (CKD), in African-Americans, some studies have also shown associations with diabetic end-stage renal disease. We investigated the association of MYH9 SNPs with renal traits in a mixed-ancestry South African population prone to diabetes. Research Design and Methods Three SNPs known to be associated with CKD (rs4821480, rs5756152 and rs12107) were genotyped using Taqman assay in 716 adults (198 with diabetes) from the Bellville-South community, Cape Town. Glomerular filtration rate was estimated (eGFR) and urinary albumin/creatinine ratio (ACR) assessed. Multivariable regressions were used to relate the SNPs with renal traits. Results Mean age was 53.6 years, with the expected differences observed in characteristics by diabetic status. Significant associations were found between rs575152 and serum creatinine, and eGFR in the total population, and in diabetic participants (all p≤0.003), but not in non-diabetics (all p≥0.16), with significant interactions by diabetes status (interaction-p≤0.009). The association with ACR was borderline in diabetic participants (p = 0.05) and non-significant in non-diabetics (p = 0.85), with significant interaction (interaction p = 0.02). rs12107 was associated with fasting-, 2-hour glucose and HbA1c in diabetic participants only (interaction-p≤0.003), but not with renal traits. Conclusion MYH9 SNPs were associated with renal traits only in diabetic participants in this population. Our findings and other studies suggest that MYH9 may have a broader genetic risk effect on kidney diseases. PMID:23285077

  11. Treatment of metabolic acidosis in patients with stage 3 chronic kidney disease with fruits and vegetables or oral bicarbonate reduces urine angiotensinogen and preserves glomerular filtration rate.

    PubMed

    Goraya, Nimrit; Simoni, Jan; Jo, Chan-Hee; Wesson, Donald E

    2014-11-01

    Alkali therapy of metabolic acidosis in patients with chronic kidney disease (CKD) with plasma total CO2 (TCO2) below 22 mmol/l per KDOQI guidelines appears to preserve estimated glomerular filtration rate (eGFR). Since angiotensin II mediates GFR decline in partial nephrectomy models of CKD and even mild metabolic acidosis increases kidney angiotensin II in animals, alkali treatment of CKD-related metabolic acidosis in patients with plasma TCO2 over 22 mmol/l might preserve GFR through reduced kidney angiotensin II. To test this, we randomized 108 patients with stage 3 CKD and plasma TCO2 22-24 mmol/l to Usual Care or interventions designed to reduce dietary acid by 50% using sodium bicarbonate or base-producing fruits and vegetables. All were treated to achieve a systolic blood pressure below 130 mm Hg with regimens including angiotensin converting enzyme inhibition and followed for 3 years. Plasma TCO2 decreased in Usual Care but increased with bicarbonate or fruits and vegetables. By contrast, urine excretion of angiotensinogen, an index of kidney angiotensin II, increased in Usual Care but decreased with bicarbonate or fruits and vegetables. Creatinine-calculated and cystatin C-calculated eGFR decreased in all groups, but loss was less at 3 years with bicarbonate or fruits and vegetables than Usual Care. Thus, dietary alkali treatment of metabolic acidosis in CKD that is less severe than that for which KDOQI recommends therapy reduces kidney angiotensin II activity and preserves eGFR. PMID:24694986

  12. Comparison of predictive accuracy of teicoplanin concentration using creatinine clearance and glomerular filtration rate estimated by serum creatinine or cystatin C.

    PubMed

    Kozono, Aki; Hiraki, Yoichi; Adachi, Rui; Nagano, Masahisa; Inoue, Daisuke; Tsuji, Yasuhiro; Kamimura, Hidetoshi; Karube, Yoshiharu

    2016-05-01

    We compared the predictive accuracy of TEIC concentrations (TEIC_conc) calculated using either serum cystatin C (CysC) or serum creatinine (SCr) and the population mean method using the mean population parameter of TEIC_conc for Japan. We also compared the predicted TEIC_conc to measured TEIC_conc. Creatinine clearance (CLCr) predicted using the Cockcroft-Gault (C&G) equation with SCr was 45.23 mL/min (interquartile range [IQR]: 32.12-58.28), and the glomerular filtration rate (GFR) predicted using the Hoek equation with CysC was 45.23 mL/min (IQR: 35.40-53.79). The root mean-squared prediction error (IQR) based on CLCr predicted using the C&G equation with SCr was 6.88 (3.80-9.96) μg/mL, and that based on GFR predicted using the Hoek equation with CysC was 6.72 (3.77-9.68) μg/mL. Predicted TEIC_conc did not differ significantly between the two methods. The predictive accuracy of the TEIC_conc using the Hoek equation with CysC was similar to that of CLCr using the C&G equation with SCr. These findings suggest that the predictive accuracy of the TEIC_conc using CLCr based on the G&G equation and SCr might be sufficient for the initial dose adjustment of TEIC. Given that we were unable to confirm that CysC is the optimal method for predicting TEIC_conc, the expensive measurement of CysC might not be necessary. PMID:26923258

  13. Glomerular cell crosstalk

    PubMed Central

    Lennon, Rachel; Hosawi, Salman

    2016-01-01

    Purpose of review Glomerular filtration occurs in specialized, microscopic organelles. Each glomerulus contains unique cells and these cooperate to maintain normal filtration. Phenomenal adaptation is required for the glomerulus to respond to variable mechanical loads and this adaptation requires efficient communication between the resident cells. This review will focus on the latest discoveries related to signalling events that mediate the crosstalk between glomerular cells, and detail how disease processes can influence normal regulation. Recent findings New data indicate that the crosstalk between glomerular cells involves an increasing number of secreted signalling ligands that act in an autocrine or paracrine fashion. Furthermore, extended roles for some of the classical signalling molecules have been described and there is emerging evidence of therapeutic strategies to manipulate cellular crosstalk. The glomerular extracellular matrix harbours many of these signalling ligands, acting as a reservoir and presenting ligands to cell surface receptors. Signals can also be transferred between cells by extracellular vesicles and this is an emerging concept in cellular crosstalk. Summary Recent discoveries are building our understanding about glomerular cell crosstalk, and this review focuses on growth factors and signalling peptides, methods of delivery to target cells, and the potential for developing new therapies for glomerular disease. PMID:27027682

  14. Pathogenesis of glomerular haematuria

    PubMed Central

    Yuste, Claudia; Gutierrez, Eduardo; Sevillano, Angel Manuel; Rubio-Navarro, Alfonso; Amaro-Villalobos, Juan Manuel; Ortiz, Alberto; Egido, Jesus; Praga, Manuel; Moreno, Juan Antonio

    2015-01-01

    Haematuria was known as a benign hallmark of some glomerular diseases, but over the last decade, new evidences pointed its negative implications on kidney disease progression. Cytotoxic effects of oxidative stress induced by hemoglobin, heme, or iron released from red blood cells may account for the tubular injury observed in human biopsy specimens. However, the precise mechanisms responsible for haematuria remain unclear. The presence of red blood cells (RBCs) with irregular contours and shape in the urine indicates RBCs egression from the glomerular capillary into the urinary space. Therefore glomerular haematuria may be a marker of glomerular filtration barrier dysfunction or damage. In this review we describe some key issues regarding epidemiology and pathogenesis of haematuric diseases as well as their renal morphological findings. PMID:25949932

  15. Association of estimated glomerular filtration rate and albuminuria with all-cause and cardiovascular mortality: a collaborative meta-analysis of general population cohorts

    PubMed Central

    Matsushita, Kunihiro; van der Velde, Marije; Astor, Brad C; Woodward, Mark; Levey, Andrew S; de Jong, Paul E; Coresh, Josef; Gansevoort, Ron T

    2014-01-01

    Background A comprehensive evaluation of the independent and combined associations of estimated glomerular filtration rate (eGFR) and albuminuria with mortality is required for assessment of the impact of kidney function on risk in the general population, with implications for improving the definition and staging of chronic kidney disease (CKD). Methods A collaborative meta-analysis of general population cohorts was undertaken to pool standardized data for all-cause and cardiovascular mortality. The two kidney measures and potential confounders from 14 studies (105,872 participants; 730,577 person-years) with urine albumin-to-creatinine ratio (ACR) measurements and seven studies (1,128,310 participants; 4,732,110 person-years) with urine protein dipstick measurements were modeled. Findings In ACR studies, mortality risk was unrelated to eGFR between 75-105 ml/min/1·73 m2 and increased at lower eGFR. Adjusted hazard ratios (HRs) for all-cause mortality at eGFR 60, 45, and 15 (versus 95) ml/min/1·73 m2 were 1·18 (95% CI: 1·05-1·32), 1·57 (1·39-1·78), and 3·14 (2·39-4·13), respectively. ACR was associated with mortality risk linearly on the log-log scale without threshold effects. Adjusted HRs for all-cause mortality at ACR 10, 30, and 300 (versus 5) mg/g were 1·20 (1·15-1·26), 1·63 (1·50-1·77), and 2·22 (1·97-2·51). eGFR and ACR were multiplicatively associated with mortality without evidence of interaction. Similar findings were observed for cardiovascular mortality and in dipstick studies. Interpretation Lower eGFR (<60 ml/min/1·73 m2) and higher albuminuria (ACR ≥10 mg/g) were independent predictors of mortality risk in the general population. This study provides quantitative data for using both kidney measures for risk evaluation and CKD definition and staging. PMID:20483451

  16. Measurement of glomerular filtration rate by dynamic contrast-enhanced magnetic resonance imaging using a subject-specific two-compartment model.

    PubMed

    Tipirneni-Sajja, Aaryani; Loeffler, Ralf B; Oesingmann, Niels; Bissler, John; Song, Ruitian; McCarville, Beth; Jones, Deborah P; Hudson, Melissa; Spunt, Sheri L; Hillenbrand, Claudia M

    2016-04-01

    Measuring glomerular filtration rate (GFR) by dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) as part of standard of care clinicalMRIexams (e.g., in pediatric solid tumor patients) has the potential to reduce diagnostic burden. However, enthusiasm for this relatively newGFRtest may be curbed by the limited amount of cross-calibration studies with referenceGFRtechniques and the vast variety ofMRtracer model algorithms causing confusion on the choice of model. To advanceMRI-basedGFRquantification via improvedGFRmodeling and comparison with associated(99m)Tc-DTPA-GFR, 29 long-term Wilms' tumor survivors (19.0-43.3 years, [median 32.0 ± 6.0 years]) treated with nephrectomy, nonnephrotoxic chemotherapy ± radiotherapy underwentMRIwith Gd-DTPAadministration and a(99m)Tc-DTPA GFRtest. ForDCE-MRI-basedGFRestimation, a subject-specific two-compartment (SS-2C) model was developed that uses individual hematocrit values, automatically defines subject-specific uptake intervals, and fits tracer-uptake curves by incorporating these measures. The association between reference(99m)Tc-DTPA GFRandMR-GFRs obtained bySS-2C, three published 2C uptake, and inflow-outflow models was investigated via linear regression analysis. Uptake intervals varied from 64 sec to 141 sec [96 sec ± 21 sec] and hematocrit values ranged from 30% to 49% [41% ± 4%]; these parameters can therefore not be assumed as constants in 2C modeling. OurMR-GFRestimates using theSS-2C model showed accordingly the highest correlation with(99m)Tc-DTPA-GFRs (R(2) = 0.76,P < 0.001) compared with other models (R(2)-range: 0.36-0.66). In conclusion,SS-2C modeling ofDCE-MRIdata improved the association betweenGFRobtained by(99m)Tc-DTPAand Gd-DTPA DCE-MRIto such a degree that this approach could turn into a viable, diagnosticGFRassay without radiation exposure to the patient. PMID:27081161

  17. Association of estimated glomerular filtration rate with all‐cause and cardiovascular mortality: the role of malnutrition–inflammation–cachexia syndrome

    PubMed Central

    Ou, Shuo‐Ming; Chen, Yung‐Tai; Hung, Szu‐Chun; Shih, Chia‐Jen; Lin, Chi‐Hung; Chiang, Chih‐Kang

    2016-01-01

    Abstract Background Previous studies have demonstrated that high estimated glomerular filtration rate (eGFR) is paradoxically associated with an increased risk of mortality, and the association becomes more predominant in older people. However, the role of malnutrition–inflammation–cachexia syndrome (MICS) in the association between eGFR and mortality has never been explored. Methods We conducted a community‐based cohort study using data from the Taipei City Elderly Health Examination Database, collected during the period 2001–10. All participants aged ≥65 years were included and stratified by the absence or presence of MICS, which is defined as the presence of at least one of the following markers: body mass index <22 kg/m2, serum albumin <3.0 mg/dL, or Geriatric Nutritional Risk Index (GNRI) <98. The study endpoints were all‐cause and cardiovascular mortality. Results A total of 131 354 participants were identified and categorized according to the chronic kidney disease stage based on eGFR. Compared with the reference eGFR of 60–89 mL/min/1.73 m2, the overall and cardiovascular mortality risks were markedly high in the groups with eGFR of <30 mL/min/1.73 m2 [overall: adjusted hazard ratio (aHR), 1.86; 95% confidence interval (CI), 1.72–2.00; cardiovascular: aHR, 1.87; 95% CI, 1.60–2.19] and ≥90 mL/min/1.73 m2 (overall: aHR, 1.23; 95% CI, 1.13–1.34; cardiovascular: aHR, 1.28; 95% CI, 1.06–1.54). In the absence of MICS, high eGFR was associated with lower mortality risk (aHR, 0.71; 95% CI, 0.62–0.80), and the U‐shaped relationship disappeared. Subgroup analyses produced consistent results. Conclusions MICS could influence the association observed between high eGFR and mortality in older people, particularly in those with low body mass index, albumin level, GNRI, and very low serum creatinine level. PMID:27493868

  18. [Measurement of glomerular filtration rate (GFR) after administration of iodine contrast medium with the Renalyzer PRX90 in healthy cats and cats with kidney diseases].

    PubMed

    Meyer-Lindenberg, A; Westhoff, A; Wohlsein, P; Pohlenz, J; Nolte, I

    1998-09-01

    In the present study, the measurement of the glomerular filtration rate (GFR) in the cat with the aid of an iodine contrast medium clearance with the renalyzer PRX90 is introduced. Investigations on the accuracy of measurement showed that even repeated measurement of plasma samples after two days of storage at room temperature yielded reproducible clearance results. Also, partial dilution of the plasma sample (2 ml with 1 ml Aqua bidest.) to reduce the volume of blood withdrawn still produced reliable results. Further dilution of the plasma volume (1 ml with 2 ml Aqua bidest.) however did not allow for accurate measurements. A total of 59 cats of different age and sex were included in the study. 31 cats had healthy kidneys with urea and creatinine values within the reference range, unchanged urine findings and physiologic urine protein patterns (SDS-PAGE). These cats served as reference group. The GFR reference value ascertained for these animals was 2.1 ml/min/kg BW (mean = 3.45 ml/min/kg with s = +/- 1.0 ml/min/kg). 28 cats had elevated values of urea and creatinine in the blood, as well as partially changed urine findings. For further diagnosis of renal disease, separation of urine proteins was done with the SDS-PAGE in the PhastSystem, which in all cases yielded a pathologic urine protein pattern. In 11 cases the renal disease could be further confirmed by histological investigation. GFR in these patients was clearly lowered compared with healthy cats, with measured values between 0 and 1.8 ml/min/kg. It can be concluded that the renalyzer allows reliable determination of the GFR also in the cat. To what extent measurement of the GFR is also helpful to diagnose nephropathies in the stage of compensation needs to be further investigated. In cats with high grade uremia and a GFR below 1 ml/min however, an exact calculation is not possible, since the accuracy of measurement within this range is inadequate. Thus, in severe disease no correct assessment is possible

  19. Urinary Albumin-Creatinine Ratio, Estimated Glomerular Filtration Rate, and All-Cause Mortality Among US Adults With Obstructive Lung Function

    PubMed Central

    Ford, Earl S.

    2015-01-01

    BACKGROUND Elevated urinary albumin-creatinine ratio (UACR) and decreased estimated glomerular filtration rate (eGFR) predict all-cause mortality, but whether these markers of kidney damage and function do so in adults with obstructive lung function (OLF) is unclear. The objective of this study was to examine the associations between UACR and eGFR and all-cause mortality in adults with OLF. METHODS Data of 5,711 US adults aged 40 to 79 years, including 1,390 adults with any OLF who participated in the National Health and Nutrition Examination Survey III (1988–1994), were analyzed. Mortality follow-up was conducted through 2006. RESULTS During the median follow-up of 13.7 years, 650 adults with OLF died. After maximal adjustment, mean levels of UACR were higher in adults with moderate-severe OLF (7.5 mg/g; 95% CI, 6.7–8.5) than in adults with normal pulmonary function (6.2 mg/g; 95% CI, 5.8–6.6) (P = .003) and mild OLF (6.2 mg/g; 95% CI, 5.5–6.9) (P = .014). Adjusted mean levels of eGFR were lower in adults with moderate-severe OLF (87.6 mL/min/1.73 m2; < 95% CI, 86.0–89.1) than in adults with normal lung function (89.6 mL/min/1.73 m2; < 95% CI, 88.9–90.3) (P = .015). Among adults with OLF, hazard ratios for all-cause mortality increased as levels of UACR, modeled as categorical or continuous variables, increased (maximally adjusted hazard ratio for quintile 5 vs 1: 2.23; 95% CI, 1.56–3.18). eGFR, modeled as a continuous variable but not as quintiles, was significantly associated with mortality. CONCLUSIONS UACR and eGFR, in continuous form, were associated with all-cause mortality among US adults with OLF. PMID:25079336

  20. Mortality Prediction in the Oldest Old with Five Different Equations to Estimate Glomerular Filtration Rate: The Health and Anemia Population-based Study

    PubMed Central

    Mandelli, Sara; Riva, Emma; Tettamanti, Mauro; Detoma, Paolo; Giacomin, Adriano; Lucca, Ugo

    2015-01-01

    Background Kidney function declines considerably with age, but little is known about its clinical significance in the oldest-old. Objectives To study the association between reduced glomerular filtration rate (GFR) estimated according to five equations with mortality in the oldest-old. Design Prospective population-based study. Setting Municipality of Biella, Piedmont, Italy. Participants 700 subjects aged 85 and older participating in the “Health and Anemia” Study in 2007–2008. Measurements GFR was estimated using five creatinine-based equations: the Cockcroft-Gault (C-G), Modification of Diet in Renal Disease (MDRD), MAYO Clinic, Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and Berlin Initiative Study-1 (BIS-1). Survival analysis was used to study mortality in subjects with reduced eGFR (<60 mL/min/1.73m2) compared to subjects with eGFR ≥60 mL/min/1.73m2. Results Prevalence of reduced GFR was 90.7% with the C-G, 48.1% with MDRD, 23.3% with MAYO, 53.6% with CKD-EPI and 84.4% with BIS-1. After adjustment for confounders, two-year mortality was significantly increased in subjects with reduced eGFR using BIS-1 and C-G equations (adjusted HRs: 2.88 and 3.30, respectively). Five-year mortality was significantly increased in subjects with eGFR <60 mL/min/1.73m2 using MAYO, CKD-EPI and, in a graduated fashion in reduced eGFR categories, MDRD. After 5 years, oldest old with an eGFR <30 mL/min/1.73m2 showed a significantly higher risk of death whichever equation was used (adjusted HRs between 2.04 and 2.70). Conclusion In the oldest old, prevalence of reduced eGFR varies noticeably depending on the equation used. In this population, risk of mortality was significantly higher for reduced GFR estimated with the BIS-1 and C-G equations over the short term. Though after five years the MDRD appeared on the whole a more consistent predictor, differences in mortality prediction among equations over the long term were less apparent. Noteworthy, subjects with

  1. A pilot study to assess the feasibility of transcutaneous glomerular filtration rate measurement using fluorescence-labelled sinistrin in dogs and cats.

    PubMed

    Steinbach, Sarah; Krolop, Nora; Strommer, Sellyn; Herrera-Pérez, Zeneida; Geraci, Stefania; Friedemann, Jochen; Gretz, Norbert; Neiger, Reto

    2014-01-01

    In dogs and cats an assessment of renal function is often needed, however, existing methods including urine and plasma clearances are invasive, cumbersome and time consuming. This pilot study evaluated the feasibility of a transcutaneous glomerular filtration rate (GFR) measurement in dogs and cats. Additionally the optimal dose and location for the transcutaneous measurement device were investigated. Renal elimination of fluorescein-isothiocyanate-labelled sinistrin (FITC-S) was measured transcutaneously for 4 hours. The procedures were performed in awake, freely moving animals using escalating doses of FITC-S (10 mg/kg, 30 mg/kg, 50 mg/kg) with a wash-out period of at least 24 h in between. Multiple devices were placed on each animal. The resulting FITC-S disappearance curves were visually assessed to determine the most suitable location and the appropriate dose to reach an adequate transcutaneous peak signal for kinetic analysis. In both species 30 mg/kg were adequate for kinetic calculation. The most suitable place for the device was the lateral thoracic wall in dogs and the ventral abdominal wall in cats, respectively. Transcutaneous FITC-S clearance was then repeated using the optimal dose and location and in parallel with an additional plasma sinistrin clearance. Plasma elimination half-lives [min] were 26, 31 and 35, and corresponding transcutaneous elimination half-lives [min] were 26, 34 and 55, respectively in the dogs. Plasma elimination half-lives [min] were 51, 60 and 61, and corresponding transcutaneous elimination half-lives [min] were 75, 96 and 83, respectively in the cats. In conclusion, transcutaneous FITC-S clearance is a feasible method for the assessment of GFR in awake dogs and cats. It is noninvasive, well tolerated and easy to perform even in a clinical setting with results being readily available. A dose of 30 mg/kg of FITC-S seems adequate for kinetic assessment. Further studies are now needed to establish reference values and evaluate

  2. Glomerular filtration rate after alpha-radioimmunotherapy with 211At-MX35-F(ab')2: a long-term study of renal function in nude mice.

    PubMed

    Bäck, Tom; Haraldsson, Börje; Hultborn, Ragnar; Jensen, Holger; Johansson, Martin E; Lindegren, Sture; Jacobsson, Lars

    2009-12-01

    Besides bone marrow, the kidneys are often dose-limiting organs in internal radiotherapy. The effects of high-linear energy transfer (LET) radiation on the kidneys after alpha-radioimmunotherapy (alpha-RIT) with the alpha-particle emitter, (211)At, were studied in nude mice by serial measurements of the glomerular filtration rate (GFR). The renal toxicity was evaluated at levels close to the dose limit for the bone marrow and well within the range for therapeutic efficacy on tumors. Astatinated MX35-F(ab')(2) monoclonal antibodies were administered intravenously to nude mice. Both non-tumor-bearing animals and animals bearing subcutaneous xenografts of the human ovarian cancer cell line, OVCAR-3, were used. The animals received approximately 0.4, 0.8, or 1.2 MBq in one, two, or three fractions. The mean absorbed doses to the kidneys ranged from 1.5 to 15 Gy. The renal function was studied by serial GFR measurements, using plasma clearance of (51)Cr-EDTA, up to 67 weeks after the first astatine injection. A dose-dependent effect on GFR was found and at the time interval 8-30 weeks after the first administration of astatine, the absorbed doses causing a 50% decrease in GFR were 16.4 +/- 3.3 and 14.0 +/- 4.1 Gy (mean +/- SEM), tumor- and non-tumor-bearing animals, respectively. The reduction in GFR progressed with time, and at the later time interval, (31-67 weeks) the corresponding absorbed doses were 7.5 +/- 2.4 and 11.3 +/- 2.3 Gy, respectively, suggesting that the effects of radiation on the kidneys were manifested late. Examination of the kidney sections showed histologic changes that were overall subdued. Following alpha-RIT with (211)At-MX35-F(ab')(2) at levels close to the dose limit of severe myelotoxicity, the effects found on renal function were relatively small, with only minor to moderate reductions in GFR. These results suggest that a mean absorbed dose to the kidneys of approximately 10 Gy is acceptable, and that the kidneys would not be the primary

  3. Relationship between Kidney Dysfunction and Ischemic Stroke Outcomes: Albuminuria, but Not Estimated Glomerular Filtration Rate, Is Associated with the Risk of Further Vascular Events and Mortality after Stroke

    PubMed Central

    Lee, Dong-Geun

    2016-01-01

    Background and Objective Estimated glomerular filtration rate (eGFR) and albuminuria are known to be associated with ischemic stroke outcomes. In this study, we investigated the longitudinal relationships of the two markers with mortality, vascular events and functional outcomes in a stroke cohort. Methods A total of 295 patients with acute ischemic stroke were prospectively recruited in a single center between May 2012 and February 2015. Renal dysfunction was defined as a decreased eGFR (<60 mL/min/1.73 m2) or albuminuria (urine albumin-to-creatinine ratio ≥ 30 mg/g). Good functional outcome at 6 months was defined as a modified Rankin scale score ≤ 2, and the occurrence of major vascular events (stroke, acute coronary syndrome or peripheral artery occlusion) or death was monitored. The associations between renal dysfunction and mortality, major vascular events, and 6-month functional outcome were evaluated by the Cox proportional hazards model and logistic regression analysis. Unadjusted and adjusted hazards ratios (HRs), odds ratios (ORs), and 95% confidence intervals (CIs) were obtained. A Kaplan–Meier survival curve for composite adverse events (major vascular events or death) was also computed according to the presence or absence of albuminuria. Results Albuminuria, not eGFR, was significantly associated with mortality (P = 0.028; HR 2.15; 95% CI 1.09–4.25) and major vascular events (P = 0.044; HR 2.24; 95% CI 1.02–4.94) in the multivariate Cox proportional hazards models adjusting for age, sex, diabetes, hypertension, current smoking, atrial fibrillation, previous stroke, alcohol history, initial National Institutes of Health Stroke Scale (NIHSS) score and eGFR. In addition, albuminuria was negatively associated with 6-month functional outcome in the multivariate logistic regression analysis adjusting for age, sex, diabetes, hypertension, current smoking, atrial fibrillation, previous stroke, alcohol history and eGFR (P = 0.001; OR 0.36; 95% CI 0

  4. Effect of A Reduction in glomerular filtration rate after NEphrectomy on arterial STiffness and central hemodynamics: Rationale and design of the EARNEST study☆

    PubMed Central

    Moody, William E.; Tomlinson, Laurie A.; Ferro, Charles J.; Steeds, Richard P.; Mark, Patrick B.; Zehnder, Daniel; Tomson, Charles R.; Cockcroft, John R.; Wilkinson, Ian B.; Townend, Jonathan N.

    2014-01-01

    Background There is strong evidence of an association between chronic kidney disease (CKD) and cardiovascular disease. To date, however, proof that a reduction in glomerular filtration rate (GFR) is a causative factor in cardiovascular disease is lacking. Kidney donors comprise a highly screened population without risk factors such as diabetes and inflammation, which invariably confound the association between CKD and cardiovascular disease. There is strong evidence that increased arterial stiffness and left ventricular hypertrophy and fibrosis, rather than atherosclerotic disease, mediate the adverse cardiovascular effects of CKD. The expanding practice of live kidney donation provides a unique opportunity to study the cardiovascular effects of an isolated reduction in GFR in a prospective fashion. At the same time, the proposed study will address ongoing safety concerns that persist because most longitudinal outcome studies have been undertaken at single centers and compared donor cohorts with an inappropriately selected control group. Hypotheses The reduction in GFR accompanying uninephrectomy causes (1) a pressure-independent increase in aortic stiffness (aortic pulse wave velocity) and (2) an increase in peripheral and central blood pressure. Methods This is a prospective, multicenter, longitudinal, parallel group study of 440 living kidney donors and 440 healthy controls. All controls will be eligible for living kidney donation using current UK transplant criteria. Investigations will be performed at baseline and repeated at 12 months in the first instance. These include measurement of arterial stiffness using applanation tonometry to determine pulse wave velocity and pulse wave analysis, office blood pressure, 24-hour ambulatory blood pressure monitoring, and a series of biomarkers for cardiovascular and bone mineral disease. Conclusions These data will prove valuable by characterizing the direction of causality between cardiovascular and renal disease. This

  5. Reduction in Estimated Glomerular Filtration Rate (eGFR) Results in an Increased Risk of Spontaneous Hemorrhagic Transformation in Patients with Large-artery Atherosclerosis Stroke.

    PubMed

    Liu, Bian; Wang, Deren; Hao, Zilong; Li, Dan; Zhang, Junhuai; Liu, Junfeng; Liu, Ming

    2016-01-01

    The association between chronic kidney disease and spontaneous hemorrhagic transformation (HT) in patients with acute ischemic stroke is seldom reported. We performed this study to identify whether reduced estimated glomerular filtration rate (eGFR) is associated with spontaneous HT in acute ischemic stroke patients, and examine whether the association depends on stroke etiology. Patients diagnosed with acute ischemic stroke whose serum creatinine levels at admission were available were consecutively and prospectively enrolled in the Chengdu Stroke Registry Database. All were analyzed on admission by cranial computed tomography (CT) scanning, followed by regular magnetic resonance imaging (MRI) 2-3 days later and afterwards CT scan if neurological symptoms deteriorated. HT was defined based on the MRI or later CT, and eGFR was calculated using the Modification of Diet in Renal Disease equation. Univariate analysis and multivariable logistic regression were performed to determine whether reduced eGFR, defined as < 60 ml/min/1.73m2, was associated with spontaneous HT. The association was also assessed in subgroups of patients classified according to the criteria of the Trial of Org 10172 in Acute Stroke Treatment (TOAST). Of the 1,645 patients enrolled, 123 (7.5%) developed spontaneous HT and 215 (13.1%) had reduced eGFR. Reduced eGFR was significantly associated with increased risk of spontaneous HT in all ischemic stroke patients (OR 1.821, 95% CI 1.081 to 3.06, P=0.024), and in the subgroup of large artery atherosclerosis, not in the cardio-embolism stroke group (OR 1.588, 95% CI 0.642 to 3.782, P=0.327). Reduced eGFR did not increase the risk of symptomatic hemorrhagic transformation (OR 0.937, 95%CI 0.247 to 3.577, P=0.924). In conclusion, reduced eGFR was significantly associated with increased risk of spontaneous HT in all ischemic stroke patients, and in large artery atherosclerosis, not in cardio-embolism stroke. Reduced eGFR did not increase the risk of

  6. [Methods for determining the glomerular filtration rate in experiments with small animals: position report of the Animal Experiment Diagnosis of Kidney Function Study Group of the Society of Nephrology of East Germany].

    PubMed

    Hagemann, I; Wüstenberg, P W

    1987-10-01

    The methods of the investigation of the glomerular filtration rate (GFR) in the animal experiment on cats and rats used at present are demonstrated as survey and the results of the basic investigations are compared. The values in cats lie between 20 and 30 ml/min/100 g kidney, in rats GFR values are between 0.6 and 1.0 ml/min/100 g body mass and 0.6-0.3 ml/min/1 g kidney. The basic values are essentially influenced by the experimental conditions and determination methods so that only clearance values within the working team concerned are comparable. PMID:3433988

  7. Sexual differences in glomerular ultrafiltration: effect of androgen administration in ovariectomized rats.

    PubMed

    Blantz, R C; Peterson, O W; Blantz, E R; Wilson, C B

    1988-03-01

    The glomerular ultrafiltration rate varies as a function of age and sex. To further elucidate the basis for the sexual difference, an androgen [Deca-Durabolin (DECA)] was administered to female ovariectomized rats, and glomerular hemodynamics were evaluated by renal micropuncture after 6 and 16 weeks of therapy. Results were compared to those in control ovariectomized female rats injected with vehicle. Therapy did not produce significant differences in body weight, but kidney size was modestly increased in DECA-treated rats at 6 weeks (0.68 +/- 0.03 vs. 0.86 +/- 0.03 g wet weight; P less than 0.05); at 16 weeks major differences in renal size were documented (0.69 +/- 0.03 vs. 1.18 +/- 0.05 g wet weight; P less than 0.01). The increase in size was primarily due to tubular hypertrophy, with more modest increases in glomerular size. After 6 weeks of therapy, the single nephron glomerular filtration rate (SNGFR) was increased in DECA-treated ovariectomized rats (24.8 +/- 1.0 vs. 32.9 +/- 1.1 nl/min; P less than 0.01). Whole kidney glomerular filtration rate also rose in proportion to increases in kidney size. The greater SNGFR was attributed to higher rates of nephron plasma flow and a numerical increase in the glomerular ultrafiltration coefficient. However, after 16 weeks of androgen therapy, in spite of marked renal hypertrophy, SNGFR did not further rise in proportion to renal size, and the rate of nephron plasma flow and the glomerular ultrafiltration coefficient actually fell relative to those in control untreated rats. Light microscopic evaluation of renal tissue revealed no abnormalities in DECA-treated rats. Thus, 6-week androgen therapy to ovariectomized female rats increased both glomerular ultrafiltration rates and renal size. However, with prolonged administration a glomerular dysfunction may have ensued whereby glomerular ultrafiltration was dissociated from increases in renal size. PMID:3342752

  8. Glomerular nephrotoxicity of aminoglycosides

    SciTech Connect

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

    2007-08-15

    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.

  9. Estimated Glomerular Filtration Rate Trajectories in HIV-Infected Subjects Treated With Different Ritonavir-Boosted Protease Inhibitors and Tenofovir Disoproxil Fumarate or Abacavir.

    PubMed

    Gianotti, Nicola; Galli, Laura; Poli, Andrea; Salpietro, Stefania; Nozza, Silvia; Carbone, Alessia; Merli, Marco; Ripa, Marco; Lazzarin, Adriano; Castagna, Antonella

    2016-05-01

    The aim of the study was to evaluate in human immunodeficiency virus (HIV)-infected patients estimated glomerular filtration rate (eGFR) trajectories during treatment with different protease inhibitors (PIs) or a non-nucleoside reverse transcriptase inhibitor (NNRTI) plus tenofovir (TDF) or abacavir (ABC) and lamivudine or emtricitabine (xTC).Retrospective study of patients followed at a single clinical center; all patients who started TDF or ABC for the first time with a NNRTI or lopinavir/r (LPV/r) or atazanavir/r (ATV/r) or darunavir/r (DRV/r), for whom at least 1 eGFR value before the start and during the studied treatment was known, were included in this analysis. eGFR was calculated by means of the CKD-EPI formula. Univariate and multivariate mixed linear model (MLM) was applied to estimate eGFR slope with the considered antiretroviral treatment.In the 1658 patients treated with TDF/xTC (aged 43 [37-48] years, with an eGFR of 105 [96; 113] mL/min/1.73 m, 80% males, 92% Caucasians, 10% coinfected with HCV, 4% with diabetes, 11% with hypertension, 38% naive for antiretroviral therapy (ART), 37% with HIV-RNA <50 copies/mL) the median follow-up was 2.5 (1.2-4.6) years. Their adjusted eGFR slopes (95% CI) were -1.26 (-1.58; -0.95), -0.43 (-1.20; +0.33), -0.86 (-1.28; -0.44), and -0.20 (-0.42; +0.02) mL/min/1.73 m per year in patients treated with ATV/r, DRV/r, LPV/r, and NNRTI, respectively. Patients receiving ATV/r or LPV/r had a greater adjusted decline in eGFR compared with those receiving NNRTIs (difference -1.06 [-1.44; -0.69] mL/min/1.73 m per year, P <0.001; and -0.66 [-1.13; -0.20] mL/min/1.73 m per year, P = 0.005, respectively); adjusted eGFR slopes were similar in patients receiving DRV/r and in those receiving NNRTIs. Patients receiving ATV/r had a greater adjusted eGFR decline than those treated with DRV/r (difference -0.83 [-1.65; -0.02] mL/min/1.73 m per year; P = 0.04), but not than those receiving LPV/r; no significant difference was

  10. Estimated Glomerular Filtration Rate Trajectories in HIV-Infected Subjects Treated With Different Ritonavir-Boosted Protease Inhibitors and Tenofovir Disoproxil Fumarate or Abacavir

    PubMed Central

    Gianotti, Nicola; Galli, Laura; Poli, Andrea; Salpietro, Stefania; Nozza, Silvia; Carbone, Alessia; Merli, Marco; Ripa, Marco; Lazzarin, Adriano; Castagna, Antonella

    2016-01-01

    Abstract The aim of the study was to evaluate in human immunodeficiency virus (HIV)-infected patients estimated glomerular filtration rate (eGFR) trajectories during treatment with different protease inhibitors (PIs) or a non-nucleoside reverse transcriptase inhibitor (NNRTI) plus tenofovir (TDF) or abacavir (ABC) and lamivudine or emtricitabine (xTC). Retrospective study of patients followed at a single clinical center; all patients who started TDF or ABC for the first time with a NNRTI or lopinavir/r (LPV/r) or atazanavir/r (ATV/r) or darunavir/r (DRV/r), for whom at least 1 eGFR value before the start and during the studied treatment was known, were included in this analysis. eGFR was calculated by means of the CKD-EPI formula. Univariate and multivariate mixed linear model (MLM) was applied to estimate eGFR slope with the considered antiretroviral treatment. In the 1658 patients treated with TDF/xTC (aged 43 [37–48] years, with an eGFR of 105 [96; 113] mL/min/1.73 m2, 80% males, 92% Caucasians, 10% coinfected with HCV, 4% with diabetes, 11% with hypertension, 38% naive for antiretroviral therapy (ART), 37% with HIV-RNA <50 copies/mL) the median follow-up was 2.5 (1.2–4.6) years. Their adjusted eGFR slopes (95% CI) were −1.26 (−1.58; −0.95), −0.43 (−1.20; +0.33), −0.86 (−1.28; −0.44), and −0.20 (−0.42; +0.02) mL/min/1.73 m2 per year in patients treated with ATV/r, DRV/r, LPV/r, and NNRTI, respectively. Patients receiving ATV/r or LPV/r had a greater adjusted decline in eGFR compared with those receiving NNRTIs (difference −1.06 [−1.44; −0.69] mL/min/1.73 m2 per year, P <0.001; and −0.66 [−1.13; −0.20] mL/min/1.73 m2 per year, P = 0.005, respectively); adjusted eGFR slopes were similar in patients receiving DRV/r and in those receiving NNRTIs. Patients receiving ATV/r had a greater adjusted eGFR decline than those treated with DRV/r (difference −0.83 [−1.65; −0.02] mL/min/1.73 m2 per year; P = 0.04), but not

  11. Association of Estimated Glomerular Filtration Rate with Hemoglobin Level in Korean Adults: The 2010–2012 Korea National Health and Nutrition Examination Survey

    PubMed Central

    Han, Sang Youb; Oh, Se Won; Hong, Jae Won; Yi, Seong Yoon; Noh, Jung Hyun; Lee, Hye Ran; Kim, Dong-Jun

    2016-01-01

    Purpose Little is known about anemia in patients with early renal dysfunction. We aimed to investigate the association of hemoglobin level and anemia prevalence with estimated glomerular filtration rate (eGFR) decline using a nation-wide representative sample of the adult Korean population. Methods In total, 17,373 participants (7,296 men; weighted n = 18,330,187; mean age, 44.2±0.3 years; 9,886 women, weighted n = 18,317,454; mean age, 46.9±0.3 years) were included. eGFR was divided into 5 groups: Group 1, ≥105; Group 2, 90–104; 75–89; Group 4, 60–74; and Group 5, <60 mL/min/1.73m2. Results The weighted anemia prevalence rates were 2.6% in men and 12.8% in women. In men, the weighted hemoglobin level increased with a decrease in eGFR; this value peaked at an eGFR of 60–89 mL/min/1.73m2 and decreased thereafter at an eGFR of <60 mL/min/1.73m2 (15.19±0.03, 15.35±0.03, 15.53±0.03, 15.52±0.06, and 14.90±0.12 g/dL from Groups 1 to 5) after adjustment for age, college graduation, cancer history, current smoking, waist circumference, serum cholesterol level, serum triglyceride level, and diastolic blood pressure. In women, the weighted hemoglobin level increased with a decrease in eGFR; this value peaked with an eGFR of 75–89 mL/min/1.73m2 and decreased thereafter (12.90±0.03, 13.08±0.02, 13.20±0.04, 13.14±0.05, and 12.47±0.11 g/dL from Groups 1 to 5) after adjustment for menstruation, pregnancy, estrogen replacement, and the above-mentioned variables. In both sexes, the weighted prevalence of anemia with an eGFR of 60–104 mL/min/1.73m2 was significantly lower than that with an eGFR of ≥105 mL/min/1.73m2 (men, 3.2±0.4%, 1.9±0.3%, 1.8±0.3%, 2.0±0.9%, and 18.1±3.1%; women, 14.0±0.8%, 11.2±0.7%, 10.5±1.0%, 13.2±1.6%, and 32.3±3.2% from Groups 1 to 5). Conclusions We noted a compensatory increase in the hemoglobin level with a minor decline in kidney function (in the range of eGFR ≥60 mL/min/1.73m2) prior to a marked decrease in

  12. Comparison of the Schwartz and CKD-EPI Equations for Estimating Glomerular Filtration Rate in Children, Adolescents, and Adults: A Retrospective Cross-Sectional Study

    PubMed Central

    Selistre, Luciano; Rabilloud, Muriel; Cochat, Pierre; de Souza, Vandréa; Iwaz, Jean; Lemoine, Sandrine; Beyerle, Françoise; Poli-de-Figueiredo, Carlos E.; Dubourg, Laurence

    2016-01-01

    Background Estimating kidney glomerular filtration rate (GFR) is of utmost importance in many clinical conditions. However, very few studies have evaluated the performance of GFR estimating equations over all ages and degrees of kidney impairment. We evaluated the reliability of two major equations for GFR estimation, the CKD-EPI and Schwartz equations, with urinary clearance of inulin as gold standard. Methods and Findings The study included 10,610 participants referred to the Renal and Metabolic Function Exploration Unit of Edouard Herriot Hospital (Lyon, France). GFR was measured by urinary inulin clearance (only first measurement kept for analysis) then estimated with isotope dilution mass spectrometry (IDMS)–traceable CKD-EPI and Schwartz equations. The participants’ ages ranged from 3 to 90 y, and the measured GFRs from 3 to 160 ml/min/1.73 m2. A linear mixed-effects model was used to model the bias (mean ratio of estimated GFR to measured GFR). Equation reliability was also assessed using precision (interquartile range [IQR] of the ratio) and accuracy (percentage of estimated GFRs within the 10% [P10] and 30% [P30] limits above and below the measured GFR). In the whole sample, the mean ratio with the CKD-EPI equation was significantly higher than that with the Schwartz equation (1.17 [95% CI 1.16; 1.18] versus 1.08 [95% CI 1.07; 1.09], p < 0.001, t-test). At GFR values of 60–89 ml/min/1.73 m2, the mean ratios with the Schwartz equation were closer to 1 than the mean ratios with the CKD-EPI equation whatever the age class (1.02 [95% CI 1.01; 1.03] versus 1.15 [95% CI 1.13; 1.16], p < 0.001, t-test). In young adults (18–40 y), the Schwartz equation had a better precision and was also more accurate than the CKD-EPI equation at GFR values under 60 ml/min/1.73 m2 (IQR: 0.32 [95% CI 0.28; 0.33] versus 0.40 [95% CI 0.36; 0.44]; P30: 81.4 [95% CI 78.1; 84.7] versus 63.8 [95% CI 59.7; 68.0]) and also at GFR values of 60–89 ml/min/1.73 m2. In all patients

  13. Elevated resistin levels in chronic kidney disease are associated with decreased glomerular filtration rate and inflammation, but not with insulin resistance.

    PubMed

    Axelsson, J; Bergsten, A; Qureshi, A R; Heimbürger, O; Bárány, P; Lönnqvist, F; Lindholm, B; Nordfors, L; Alvestrand, A; Stenvinkel, P

    2006-02-01

    In the present study, we explore the role of decreased renal function and a genetic polymorphism on the recently discovered protein resistin, apparently able to inhibit hepatic insulin action in mice. We also investigate possible links with inflammation and the insulin resistance present in patients with chronic kidney disease (CKD). This is a post hoc, cross-sectional study comparing 239 prevalent CKD patients with varying degrees of renal function impairment with an age- and gender-matched randomly selected control group of 25 individuals. Glomerular filtration rate (GFR) was estimated by the mean of urea and creatinine clearance (24-h urine samples) (n=204) or by iohexol clearance (n=60). Plasma analysis of blood lipids, insulin, glucose, inflammatory markers (high-sensitivity C-reactive protein, interleukin-6, tumor necrosis factor-alpha, vascular cellular adhesion molecule, intercellular adhesion molecule) and resistin (kit from LINCO Research, St Charles, MS) was performed using commercially available assays or routine methods. Insulin resistance was estimated by quantitative insulin-sensitivity check index (QUICKI) and homeostasis model assessment for insulin resistance (HOMA-IR) and body composition by dual-energy X-ray absorptiometry. Genotyping of a C/G promoter single nucleotide polymorphism (n=168) at position -180 of the resistin gene was performed by PyroSequencing. Serum levels of resistin were markedly elevated in the CKD patients with both advanced (39.9+/-1.3 ng/ml) and mild to moderate (23.2+/-1.0 ng/ml) renal function impairment, as compared to controls (8.5+/-0.7 ng/ml; P<0.001). In a multiple linear regression model in patients (adjusted r(2)=0.60), only GFR (beta=3.4; P<0.0001), lean body mass (beta=2.2; P<0.001) and the inflammatory markers were independently associated with circulating resistin levels. There was a weak but significant impact of -180 C/G genotype on plasma levels of resistin (median 43.0+/-2.4 ng/ml in CC, 37.5+/-2.0 ng

  14. Glomerular disease.

    PubMed

    Vaden, Shelly L

    2011-08-01

    Glomerular diseases are a leading cause of chronic kidney disease in dogs but seem to be less common in cats. Glomerular diseases are diverse, and a renal biopsy is needed to determine the specific glomerular disease that is present in any animal. Familial glomerulopathies occur in many breeds of dogs. However, most dogs with glomerular disease have acquired glomerular injury that is either immune-complex mediated or due to systemic factors, both of which are believed to be the result of a disease process elsewhere in the body (i.e., neoplastic, infectious, and noninfectious inflammatory disorders). A thorough clinical evaluation is indicated in all dogs suspected of having glomerular disease and should include an extensive evaluation for potential predisposing disorders. Nonspecific management of dogs with glomerular disease can be divided into 3 major categories: (1) treatment of potential predisposing disorders, (2) management of proteinuria, and (3) management of uremia and other complications of glomerular disease and chronic kidney disease. Specific management of specific glomerular diseases has not been fully studied in dogs. However, it may be reasonable to consider immunosuppressive therapy in dogs that have developed a form of glomerulonephritis secondary to a steroid-responsive disease (e.g., systemic lupus erythematosus) or have immune-mediated lesions that have been documented in renal biopsy specimens. Appropriate patient monitoring during therapy is important for maximizing patient care. The prognosis for dogs and cats with glomerular disease is variable and probably dependent on a combination of factors. The purpose of this article is to discuss the general diagnosis and management of dogs with glomerular disease. PMID:21782143

  15. Beta1 integrin expression by podocytes is required to maintain glomerular structural integrity.

    PubMed

    Pozzi, Ambra; Jarad, George; Moeckel, Gilbert W; Coffa, Sergio; Zhang, Xi; Gewin, Leslie; Eremina, Vera; Hudson, Billy G; Borza, Dorin-Bogdan; Harris, Raymond C; Holzman, Lawrence B; Phillips, Carrie L; Fassler, Reinhard; Quaggin, Susan E; Miner, Jeffrey H; Zent, Roy

    2008-04-15

    Integrins are transmembrane heteromeric receptors that mediate interactions between cells and extracellular matrix (ECM). beta1, the most abundantly expressed integrin subunit, binds at least 12 alpha subunits. beta1 containing integrins are highly expressed in the glomerulus of the kidney; however their role in glomerular morphogenesis and maintenance of glomerular filtration barrier integrity is poorly understood. To study these questions we selectively deleted beta1 integrin in the podocyte by crossing beta1(flox/flox) mice with podocyte specific podocin-cre mice (pod-Cre), which express cre at the time of glomerular capillary formation. We demonstrate that podocyte abnormalities are visualized during glomerulogenesis of the pod-Cre;beta1(flox/flox) mice and proteinuria is present at birth, despite a grossly normal glomerular basement membrane. Following the advent of glomerular filtration there is progressive podocyte loss and the mice develop capillary loop and mesangium degeneration with little evidence of glomerulosclerosis. By 3 weeks of age the mice develop severe end stage renal failure characterized by both tubulointerstitial and glomerular pathology. Thus, expression of beta1 containing integrins by the podocyte is critical for maintaining the structural integrity of the glomerulus. PMID:18328474

  16. Associations of blood lead, cadmium, and mercury with estimated glomerular filtration rate in the Korean general population: Analysis of 2008-2010 Korean National Health and Nutrition Examination Survey data

    SciTech Connect

    Kim, Yangho; Lee, Byung-Kook

    2012-10-15

    Introduction: The objective of this study was to evaluate associations between blood lead, cadmium, and mercury levels with estimated glomerular filtration rate in a general population of South Korean adults. Methods: This was a cross-sectional study based on data obtained in the Korean National Health and Nutrition Examination Survey (KNHANES) (2008-2010). The final analytical sample consisted of 5924 participants. Estimated glomerular filtration rate (eGFR) was calculated using the MDRD Study equation as an indicator of glomerular function. Results: In multiple linear regression analysis of log2-transformed blood lead as a continuous variable on eGFR, after adjusting for covariates including cadmium and mercury, the difference in eGFR levels associated with doubling of blood lead were -2.624 mL/min per 1.73 m Superscript-Two (95% CI: -3.803 to -1.445). In multiple linear regression analysis using quartiles of blood lead as the independent variable, the difference in eGFR levels comparing participants in the highest versus the lowest quartiles of blood lead was -3.835 mL/min per 1.73 m Superscript-Two (95% CI: -5.730 to -1.939). In a multiple linear regression analysis using blood cadmium and mercury, as continuous or categorical variables, as independent variables, neither metal was a significant predictor of eGFR. Odds ratios (ORs) and 95% CI values for reduced eGFR calculated for log2-transformed blood metals and quartiles of the three metals showed similar trends after adjustment for covariates. Discussion: In this large, representative sample of South Korean adults, elevated blood lead level was consistently associated with lower eGFR levels and with the prevalence of reduced eGFR even in blood lead levels below 10 {mu}g/dL. In conclusion, elevated blood lead level was associated with lower eGFR in a Korean general population, supporting the role of lead as a risk factor for chronic kidney disease.

  17. Effect of background region of interest and time-interval selection on glomerular filtration ratio estimation by percentage dose uptake of (99m)Tc-DTPA in comparison with (51)Cr-EDTA clearance in healthy cats.

    PubMed

    Debruyn, Katrien; Vandermeulen, Eva; Saunders, Jimmy H; Dobbeleir, André A; Ham, Hamphrey R; Peremans, Kathelijne

    2013-08-01

    Evaluation of glomerular function is a useful part of the diagnostic approach in animals suspected of having renal disease. Time-interval and background region of interest (bg ROI) selection are determining factors when calculating the glomerular filtration ratio (GFR) based on percentage uptake of (99m)technetium-labelled diethylene triamine penta-acetic acid ((99m)Tc-DTPA). Therefore, three different time intervals (60-120 s, 120-180 s, 60-180 s) and three different bg ROIs (C-shape, caudolateral, cranial + caudal) were investigated. In addition, global GFRs based on percentage dose uptake of (99m)Tc-DTPA for the different time-intervals and bg ROIs were compared with the global GFR based on (51)chromium-ethylene diaminic tetra-acetic acid ((51)Cr-EDTA) plasma clearance in nine healthy European domestic shorthair cats. Paired Student's t-tests and linear regression analysis were used to analyse the data. Different time intervals seemed to cause significant variation (P <0.01) in absolute GFR values, regardless of the choice of bg ROI. Significant differences (P <0.01) between bg ROIs were only observed in the 120-180s time interval between the C-shape and cranial + caudal bg ROI, and between the caudolateral and cranial + caudal bg ROI. The caudolateral bg ROI in the 60-180 s time interval showed the highest correlation coefficient (r = 0.882) between (99m)Tc-DTPA and (51)Cr-EDTA, although a significant difference (P <0.05) was present between both techniques. PMID:23349527

  18. The Impact of Admission Serum Creatinine Derived Estimated Glomerular Filtration Rate on Major Adverse Cardiac Events in ST-Segment Elevation Myocardial Infarction Patients Undergoing Primary Percutaneous Coronary Intervention

    PubMed Central

    Uluganyan, Mahmut; Karaca, Gurkan; Ulutas, Turker Kemal; Ekmekci, Ahmet; Tusun, Eyup; Murat, Ahmet; Koroglu, Bayram; Uyarel, Huseyin; Bakhshaliyev, Nijad; Eren, Mehmet

    2016-01-01

    Background The impact of Cockroft-Gault (C-G) derived estimated glomerular filtration rate (eGFR) on mortality and major adverse cardiac events (MACEs) in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI) was assessed. Methods A total of 884 patients were classified into four categories according to admission creatine derived eGFR: < 60, 60 - < 90, 90 - < 120, and ≥ 120 mL/min/1.73 m2. Results In-hospital and long-term MACEs were significantly higher in eGFR < 60 mL/min/1.73 m2 subgroup (P < 0.001 and P = 0.028). Multivariate analysis demonstrated 7.78-fold (95% CI: 0.91 - 66.8) higher mortality risk in eGFR < 60 mL/min/1.73 m2 subgroup. Conclusion As an easily applicable bedside method, C-G derived eGFR could be important for prediction of in-hospital and long-term mortality and MACE in STEMI patients undergoing primary PCI. PMID:26985253

  19. Vascular Growth Factors and Glomerular Disease.

    PubMed

    Bartlett, Christina S; Jeansson, Marie; Quaggin, Susan E

    2016-01-01

    The glomerulus is a highly specialized microvascular bed that filters blood to form primary urinary filtrate. It contains four cell types: fenestrated endothelial cells, specialized vascular support cells termed podocytes, perivascular mesangial cells, and parietal epithelial cells. Glomerular cell-cell communication is critical for the development and maintenance of the glomerular filtration barrier. VEGF, ANGPT, EGF, SEMA3A, TGF-β, and CXCL12 signal in paracrine fashions between the podocytes, endothelium, and mesangium associated with the glomerular capillary bed to maintain filtration barrier function. In this review, we summarize the current understanding of these signaling pathways in the development and maintenance of the glomerulus and the progression of disease. PMID:26863327

  20. Use of 3D DCE-MRI for the estimation of renal perfusion and glomerular filtration rate: an intrasubject comparison of FLASH and KWIC with a comprehensive framework for evaluation.

    PubMed

    Eikefjord, Eli; Andersen, Erling; Hodneland, Erlend; Zöllner, Frank; Lundervold, Arvid; Svarstad, Einar; Rørvik, Jarle

    2015-03-01

    OBJECTIVE. The purpose of this article is to compare two 3D dynamic contrast-enhanced (DCE) MRI measurement techniques for MR renography, a radial k-space weighted image contrast (KWIC) sequence and a cartesian FLASH sequence, in terms of intrasubject differences in estimates of renal functional parameters and image quality characteristics. SUBJECTS AND METHODS. Ten healthy volunteers underwent repeated breath-hold KWIC and FLASH sequence examinations with temporal resolutions of 2.5 and 2.8 seconds, respectively. A two-compartment model was used to estimate MRI-derived perfusion parameters and glomerular filtration rate (GFR). The latter was compared with the iohexol GFR and the estimated GFR. Image quality was assessed using a visual grading characteristic analysis of relevant image quality criteria and signal-to-noise ratio calculations. RESULTS. Perfusion estimates from FLASH were closer to literature reference values than were the KWIC sequences. In relation to the iohexol GFR (mean [± SD], 103 ± 11 mL/min/1.73 m(2)), KWIC produced significant underestimations and larger bias in GFR values (mean, 70 ± 30 mL/min/1.73 m(2); bias = -33.2 mL/min/1.73 m(2)) compared with the FLASH GFR (110 ± 29 mL/min/1.73 m(2); bias = 6.4 mL/min/1.73 m(2)). KWIC was statistically significantly (p < 0.005) more impaired by artifacts than was FLASH (AUC = 0.18). The average signal-enhancement ratio (delta ratio) in the cortex was significantly lower for KWIC (delta ratio = 0.99) than for FLASH (delta ratio = 1.40). Other visually graded image quality characteristics and signal-to-noise ratio measurements were not statistically significantly different. CONCLUSION. Using the same postprocessing scheme and pharmacokinetic model, FLASH produced more accurate perfusion and filtration parameters than did KWIC compared with clinical reference methods. Our data suggest an apparent relationship between image quality characteristics and the degree of stability in the numeric model

  1. Relationship between renal volume calculated by using multislice computed tomography and glomerular filtration rate calculated by using the Cockcroft-Gault and modification of diet in renal disease equations in living kidney donors.

    PubMed

    Adibi, Atoosa; Mortazavi, Mojgan; Shayganfar, Azin; Kamal, Sima; Azad, Roya; Aalinezhad, Marzieh

    2016-01-01

    It is essential to ascertain the state of health and renal function of potential kidney donors before organ removal. In this regard, one of the primary steps is to estimate the donor's glomerular filtration rate (GFR). For this purpose, the modification of diet in renal disease (MDRD) and the Cockcroft-Gault (CG) formulas has been used. However, these two formulas produce different results and finding new techniques with greater accuracy is required. Measuring the renal volume from computed tomography (CT) scan may be a valuable index to assess the renal function. This study was conducted to investigate the correlation between renal volume and the GFR values in potential living kidney donors referred to the multislice imaging center at Alzahra Hospital during 2014. The study comprised 66 subjects whose GFR was calculated using the two aforementioned formulas. Their kidney volumes were measured by using 64-slice CT angiography and the correlation between renal volume and GFR values were analyzed using the Statistical Package for the Social Science software. There was no correlation between the volume of the left and right kidneys and the MDRD-based estimates of GFR (P = 0.772, r = 0.036, P = 0.251, r = 0.143, respectively). A direct linear correlation was found between the volume of the left and right kidneys and the CG-based GFR values (P = 0.001, r = 0.397, P <0.001, r = 0.465, respectively). The kidney volume derived from multislice CT scan can help predict the GFR value in kidney donors with normal renal function. The limitations of our study include the small sample size and the medium resolution of 64-slice multislice scanners. Further studies with larger sample size and using higher resolution scanners are warranted to determine the accuracy of this method in potential kidney donors. PMID:27424682

  2. Individualizing Pharmacotherapy in Patients with Renal Impairment: The Validity of the Modification of Diet in Renal Disease Formula in Specific Patient Populations with a Glomerular Filtration Rate below 60 Ml/Min. A Systematic Review

    PubMed Central

    Kramers, Cornelis; Derijks, Hieronymus J.; Wensing, Michel; Wetzels, Jack F. M.

    2015-01-01

    Background The Modification of Diet in Renal Disease (MDRD) formula is widely used in clinical practice to assess the correct drug dose. This formula is based on serum creatinine levels which might be influenced by chronic diseases itself or the effects of the chronic diseases. We conducted a systematic review to determine the validity of the MDRD formula in specific patient populations with renal impairment: elderly, hospitalized and obese patients, patients with cardiovascular disease, cancer, chronic respiratory diseases, diabetes mellitus, liver cirrhosis and human immunodeficiency virus. Methods and Findings We searched for articles in Pubmed published from January 1999 through January 2014. Selection criteria were (1) patients with a glomerular filtration rate (GFR) < 60 ml/min (/1.73m2), (2) MDRD formula compared with a gold standard and (3) statistical analysis focused on bias, precision and/or accuracy. Data extraction was done by the first author and checked by a second author. A bias of 20% or less, a precision of 30% or less and an accuracy expressed as P30% of 80% or higher were indicators of the validity of the MDRD formula. In total we included 27 studies. The number of patients included ranged from 8 to 1831. The gold standard and measurement method used varied across the studies. For none of the specific patient populations the studies provided sufficient evidence of validity of the MDRD formula regarding the three parameters. For patients with diabetes mellitus and liver cirrhosis, hospitalized patients and elderly with moderate to severe renal impairment we concluded that the MDRD formula is not valid. Limitations of the review are the lack of considering the method of measuring serum creatinine levels and the type of gold standard used. Conclusion In several specific patient populations with renal impairment the use of the MDRD formula is not valid or has uncertain validity. PMID:25741695

  3. Association Between Serum Long-Chain n-3 and n-6 Polyunsaturated Fatty Acid Profiles and Glomerular Filtration Rate Assessed by Serum Creatinine and Cystatin C Levels in Japanese Community-Dwellers

    PubMed Central

    Higashiyama, Aya; Kubota, Yoshimi; Marumo, Mikio; Konishi, Masami; Yamashita, Yoshiko; Nishimura, Kunihiro; Fukuda, Yoshihiro; Okamura, Tomonori; Wakabayashi, Ichiro

    2015-01-01

    Background Plasma concentration of n-3 polyunsaturated fatty acids (PUFAs) has been reported to be associated with renal function in Western populations. However, few studies have investigated the association between serum long-chain n-3 and n-6 PUFA profiles and renal function in a Japanese population with high marine-derived long-chain n-3 PUFA intake. Methods A cross-sectional study was performed in 549 Japanese rural community-dwellers aged 40 to 64 years. In adjusted analysis of covariance, we assessed the relationship between estimated glomerular filtration rate (eGFR) and tertiles of serum long-chain n-3 and n-6 PUFA profiles ([eicosapentaenoic acid {EPA} + docosahexaenoic acid {DHA}]:arachidonic acid [AA]). GFR was estimated by Japanese specific equations using serum creatinine and cystatin C (eGFRcre and eGFRcys). Using multivariate-adjusted linear regression models, we also assessed the relationships between eGFRs and several n-3 and n-6 PUFAs, which have been suggested to be associated with renal function. Results In all participants, higher dietary fish intake as assessed by a semi-quantitative questionnaire was associated with higher serum value of (EPA+DHA):AA. Participants in the higher (EPA+DHA):AA tertiles had non-significantly higher eGFRcre and significantly higher eGFRcys (P = 0.016). In addition, eGFRcys in T2+T3 of (EPA+DHA):AA was significantly higher than that in T1 (adjusted mean eGFRcys, T1: 87 ml/min/1.73 m2, T2+T3: 91 ml/min/1.73 m2; P < 0.01). Among the PUFAs, only (EPA+DHA) was significantly associated with eGFRcys. Conclusions Serum (EPA+DHA):AA, which reflects an individual’s fish intake, might be associated with eGFRcys in Japanese community-dwellers. PMID:25728619

  4. Null mutation of the nicotinamide adenine dinucleotide phosphate-oxidase subunit p67phox protects the Dahl-S rat from salt-induced reductions in medullary blood flow and glomerular filtration rate.

    PubMed

    Evans, Louise C; Ryan, Robert P; Broadway, Elizabeth; Skelton, Meredith M; Kurth, Theresa; Cowley, Allen W

    2015-03-01

    Null mutations in the p67(phox) subunit of nicotinamide adenine dinucleotide phosphate-oxidase confer protection from salt sensitivity on Dahl salt-sensitive rats. Here, we track the sequential changes in medullary blood flow (MBF), glomerular filtration rate (GFR), urinary protein, and mean arterial pressure in SSp67(phox) null rats and wild-type littermates during 21 days of 4.0% NaCl high-salt (HS) diet. Optical fibers were implanted in the renal medulla and MBF was measured in conscious rats by laser Doppler flowmetry. Separate groups of rats were prepared with femoral venous catheters and GFR was measured by the transcutaneous assessment of fluorescein isothiocyanate-sinistrin disappearance curves. Mean arterial blood pressure was measured by telemetry. In wild-type rats, HS caused a rapid reduction in MBF, which was significantly lower than control values by HS day-6. Reduced MBF was associated with a progressive increase in mean arterial pressure, averaging 170±5 mm Hg by HS salt day-21. A significant reduction in GFR was evident on day-14 HS, after the onset of hypertension and reduced MBF. In contrast, HS had no significant effect on MBF in SSp67(phox) null rats and the pressor response to sodium was blunted, averaging 150±3 mm Hg on day-21 HS. GFR was maintained throughout the study and proteinuria was reduced. In summary, when p67(phox) is not functional in the salt-sensitive rats, HS does not cause reduced MBF and salt-sensitive hypertension is attenuated, and consequently renal injury is reduced and GFR is maintained. PMID:25489057

  5. Spironolactone use and higher hospital readmission for Medicare beneficiaries with heart failure, left ventricular ejection fraction <45%, and estimated glomerular filtration rate <45 ml/min/1.73 m(2.).

    PubMed

    Inampudi, Chakradhari; Parvataneni, Sridivya; Morgan, Charity J; Deedwania, Prakash; Fonarow, Gregg C; Sanders, Paul W; Prabhu, Sumanth D; Butler, Javed; Forman, Daniel E; Aronow, Wilbert S; Allman, Richard M; Ahmed, Ali

    2014-07-01

    Although randomized controlled trials have demonstrated benefits of aldosterone antagonists for patients with heart failure and reduced ejection fraction (HFrEF), they excluded patients with serum creatinine >2.5 mg/dl, and their use is contraindicated in those with advanced chronic kidney disease (CKD). In the present analysis, we examined the association of spironolactone use with readmission in hospitalized Medicare beneficiaries with HFrEF and advanced CKD. Of the 1,140 patients with HFrEF (EF <45%) and advanced CKD (estimated glomerular filtration rate [eGFR] <45 ml/min/1.73 m(2)), 207 received discharge prescriptions for spironolactone. Using propensity scores (PSs) for the receipt of discharge prescriptions for spironolactone, we estimated PS-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for spironolactone-associated outcomes. Patients (mean age 76 years, 49% women, 25% African-American) had mean EF 28%, mean eGFR 31 ml/min/1.73 m(2), and mean potassium 4.5 mEq/L. Spironolactone use had significant PS-adjusted association with higher risk of 30-day (HR 1.41, 95% CI 1.04 to 1.90) and 1-year (HR 1.36, 95% CI 1.13 to 1.63) all-cause readmissions. The risk of 1-year all-cause readmission was higher among 106 patients with eGFR <15 ml/min/1.73 m(2) (HR 4.75, 95% CI 1.84 to 12.28) than among those with eGFR 15 to 45 ml/min/1.73 m(2) (HR 1.34, 95% CI 1.11 to 1.61, p for interaction 0.003). Spironolactone use had no association with HF readmission and all-cause mortality. In conclusion, among hospitalized patients with HFrEF and advanced CKD, spironolactone use was associated with higher all-cause readmission but had no association with all-cause mortality or HF readmission. PMID:24846806

  6. Protein Diet Restriction Slows Chronic Kidney Disease Progression in Non-Diabetic and in Type 1 Diabetic Patients, but Not in Type 2 Diabetic Patients: A Meta-Analysis of Randomized Controlled Trials Using Glomerular Filtration Rate as a Surrogate

    PubMed Central

    Rughooputh, Mahesh Shumsher; Zeng, Rui; Yao, Ying

    2015-01-01

    Background/ Objective Studies, including various meta-analyses, on the effect of Protein Diet Restriction on Glomerular Filtration Rate (GFR) in Chronic Kidney Disease (CKD) have reported conflicting results. In this paper, we have provided an update on the evidence available on this topic. We have investigated the reasons why the effect has been inconsistent across studies. We have also compared the effect on GFR in various subgroups including type 1 diabetics, type 2 diabetics and non-diabetics. Method We searched for Randomized Controlled Trials on this intervention from MEDLINE, EMBASE, and other information sources. The PRISMA guidelines, as well as recommended meta-analysis practices were followed in the selection process, analysis and reporting of our findings. The effect estimate used was the change in mean GFR. Heterogeneity across the considered studies was explored using both subgroup analyses and meta-regression. Quality assessment was done using the Cochrane risk of bias tool and sensitivity analyses. Results 15 randomized controlled trials, including 1965 subjects, were analyzed. The pooled effect size, as assessed using random-effects model, for all the 15 studies was -0.95 ml/min/1.73m2/year (95% CI: -1.79, -0.11), with a significant p value of 0.03. The combined effect estimate for the non-diabetic and type 1 diabetic studies was -1.50 ml/min/1.73m2/year (95% CI: -2.73, -0.26) with p value of 0.02. The effect estimate for the type 2 diabetic group was -0.17 ml/min/1.73m2/year (95% CI: -1.88, 1.55) with p value of 0.85. There was significant heterogeneity across the included studies (I2 = 74%, p value for Q < 0.0001), explained by major variations in the percentage of type 2 diabetic subjects, the number of subjects and overall compliance level to diet prescribed. Conclusion Our findings suggest that protein diet restriction slows chronic renal disease progression in non-diabetic and in type 1 diabetic patients, but not in type 2 diabetic patients

  7. Exploratory Analysis for the Evaluation of Estimated Glomerular Filtration Rate, Cholesterol and Triglycerides after Switching from Tenofovir/Emtricitabine plus Atazanavir/Ritonavir (ATV/r) to Abacavir/Lamivudine plus ATV/r in Patients with Preserved Renal Function

    PubMed Central

    Postorino, Maria Concetta; Quiros-Roldan, Eugenia; Maggiolo, Franco; Di Giambenedetto, Simona; Ladisa, Nicoletta; Lapadula, Giuseppe; Lorenzotti, Silvia; Sighinolfi, Laura; Castelnuovo, Filippo; Di Pietro, Massimo; Gotti, Daria; Mazzini, Nicola; Torti, Carlo

    2016-01-01

    Background and Objectives: Renal toxicity due to tenofovir (TDF) has been largely described in patients with HIV infection. However, other antiretroviral drugs (such as atazanavir [ATV], especially when boosted by ritonavir, ATV/r) could perpetuate some degrees of renal impairment with or without TDF co-administration. Also, possible benefits of stopping TDF in patients without renal diseases is not well known. This study aimed at exploring evolution of renal function and lipid profile after switching from tenofovir/emtricitabine (TDF/FTC) to abacavir/lamivudine (ABC/3TC), maintaining the ATV/r component of the regimen. Methods: Patients in the Italian MASTER Cohort, who switched from TDF/FTC plus ATV/r to ABC/3TC plus ATV/r were included, provided that major renal diseases were not diagnosed before switching (i.e., baseline). Serum creatinine, estimated glomerular filtration rate (eGFR), total cholesterol, HDL and triglycerides were evaluated at baseline and at month 18 after switching. Results: 126 patients were selected (80% males). Patients were mostly Italians (92%). 79% had undetectable HIV-RNA and 44% were co-infected by HBV and/or HCV. Median age at switch was 47 years (IQR 43-55). A small but significant decrease in serum creatinine [from 1.06 mg/dl (SD: 0.3) to 0.94 mg/dl (SD: 0.2); p<0.001] with an improvement in eGFR [from 86.8 ml/min (SD: 33) to 96.4 ml/min (SD: 37); p<0.001] were observed in per protocol analysis at month 18. Also ITT analysis showed a decrease in mean serum creatinine [from 1.08 mg/dl (SD: 0.35) to 0.95 mg/dl (SD: 0.24); p<0.001] with an improvement in mean eGFR [from 86.9 ml/min/1.73m2 (SD: 24.11) to 95.8 ml/min/1.73m2 (SD: 19.99); p<0.001]. Total cholesterol increased [from 188 mg/dl (SD: 42) to 206 mg/dl (SD: 44); p<0.001] but also HDL increased as well [from 46 mg/dl (SD: 14) to 54 mg/dl (SD: 19); p=0.015]. An increase in triglycerides concentration was observed [from 162 mg/dl (SD: 144) to 214 mg/dl (SD: 109); p=0.027] in per

  8. Documentation of angiotensin II receptors in glomerular epithelial cells

    NASA Technical Reports Server (NTRS)

    Sharma, M.; Sharma, R.; Greene, A. S.; McCarthy, E. T.; Savin, V. J.; Cowley, A. W. (Principal Investigator)

    1998-01-01

    Angiotensin II decreases glomerular filtration rate, renal plasma flow, and glomerular capillary hydraulic conductivity. Although angiotensin II receptors have been demonstrated in mesangial cells and proximal tubule cells, the presence of angiotensin II receptors in glomerular epithelial cells has not previously been shown. Previously, we have reported that angiotensin II caused an accumulation of cAMP and a reorganization of the actin cytoskeleton in cultured glomerular epithelial cells. Current studies were conducted to verify the presence of angiotensin II receptors by immunological and non-peptide receptor ligand binding techniques and to ascertain the activation of intracellular signal transduction in glomerular epithelial cells in response to angiotensin II. Confluent monolayer cultures of glomerular epithelial cells were incubated with angiotensin II, with or without losartan and/or PD-123,319 in the medium. Membrane vesicle preparations were obtained by homogenization of washed cells followed by centrifugation. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of membrane proteins followed by multiscreen immunoblotting was used to determine the presence of angiotensin II receptor type 1 (AT1) or type 2 (AT2). Angiotensin II-mediated signal transduction in glomerular epithelial cells was studied by measuring the levels of cAMP, using radioimmunoassay. Results obtained in these experiments showed the presence of both AT1 and AT2 receptor types in glomerular epithelial cells. Angiotensin II was found to cause an accumulation of cAMP in glomerular epithelial cells, which could be prevented only by simultaneous use of losartan and PD-123,319, antagonists for AT1 and AT2, respectively. The presence of both AT1 and AT2 receptors and an increase in cAMP indicate that glomerular epithelial cells respond to angiotensin II in a manner distinct from that of mesangial cells or proximal tubular epithelial cells. Our results suggest that glomerular epithelial

  9. Reactive oxygen species as glomerular autacoids.

    PubMed

    Baud, L; Fouqueray, B; Philippe, C; Ardaillou, R

    1992-04-01

    There is considerable evidence suggesting that reactive oxygen species (ROS; superoxide anion, hydrogen peroxide, hydroxyl radical, hypochlorous acid) are implicated in the pathogenesis of toxic, ischemic, and immunologically mediated glomerular injury. The capacity of glomerular cells, especially mesangial cells, to generate ROS in response to several stimuli suggests that these autacoids may play a role in models of glomerular injury that are independent of infiltrating polymorphonuclear leukocytes and monocytes. The mechanisms whereby ROS formation results in morphologic lesions and in modifications of glomerular permeability, blood flow, and filtration rate have been inferred from in vitro studies. They involve direct and indirect injury to resident cells (mesangiolysis) and glomerular basement membrane (in concert with metalloproteases) and alteration of both the release and binding of vasoactive substances, such as bioactive lipids (e.g., prostaglandin E2, prostacyclin, thromboxane), cytokines (e.g., tumor necrosis factor alpha), and possibly endothelium-derived relaxing factor. The importance of such processes appears to be modulated by the intrinsic antioxidant defenses of the glomeruli. Further studies are needed to address the role of ROS in human glomerular diseases. PMID:1600128

  10. The cell biology of renal filtration

    PubMed Central

    Quaggin, Susan E.

    2015-01-01

    The function of the kidney, filtering blood and concentrating metabolic waste into urine, takes place in an intricate and functionally elegant structure called the renal glomerulus. Normal glomerular function retains circulating cells and valuable macromolecular components of plasma in blood, resulting in urine with just trace amounts of proteins. Endothelial cells of glomerular capillaries, the podocytes wrapped around them, and the fused extracellular matrix these cells form altogether comprise the glomerular filtration barrier, a dynamic and highly selective filter that sieves on the basis of molecular size and electrical charge. Current understanding of the structural organization and the cellular and molecular basis of renal filtration draws from studies of human glomerular diseases and animal models of glomerular dysfunction. PMID:25918223

  11. Advances in apheresis therapy for glomerular diseases.

    PubMed

    Yokoyama, Hitoshi; Wada, Takashi; Zhang, Wei; Yamaya, Hideki; Asaka, Mitsuhiro

    2007-06-01

    This article is an overview of the immunomodulatory effects of apheresis in renal diseases, especially primary and secondary glomerulonephritis, and the clinical evidence for the efficacy of apheresis therapy. Permeability factor(s) derived from circulating T cells are speculated to have a crucial role in the proteinuria of nephrotic syndrome (NS). Plasma exchange (PE); immunoadsorption plasmapheresis (IAPP), using protein A sepharose cartridges; low-density lipoprotein apheresis; and lymphocytapheresis (LCAP) have been used to remove such factors or pathogenic T cells. Other glomerular diseases induced by specific antibodies such as anti-glomerular basement membrane antibodies, anti-neutrophil cytoplasmic antibodies, and immune-complexes have also been treated with PE, double-filtration plasmapheresis, IAPP, and LCAP. Recommendations, based on the evidence from recent randomized controlled studies, have been established in apheresis therapy for various glomerular diseases. PMID:17593511

  12. Transforming growth factor-beta. Murine glomerular receptors and responses of isolated glomerular cells.

    PubMed Central

    MacKay, K; Striker, L J; Stauffer, J W; Doi, T; Agodoa, L Y; Striker, G E

    1989-01-01

    Proliferation of resident glomerular cells and the accumulation of mesangial matrix are histologic abnormalities which are observed in the course of many progressive glomerular diseases. We explored the potential regulatory effects of transforming growth factor-beta (TGF-beta) on these processes. We found that cultured mouse glomerular endothelial, mesangial, and epithelial cells as well as isolated intact rat glomeruli possess high-affinity receptors for TGF-beta. We also found that, although TGF-beta consistently inhibited the proliferation of glomerular endothelial and epithelial cells, it acted as a bifunctional regulator of mesangial cell proliferation. TGF-beta significantly increased the production of collagen and fibronectin by glomerular mesangial cells whereas only fibronectin production was augmented in glomerular epithelial cells. The presence of TGF-beta receptors on intact glomeruli and on each glomerular cell type and the demonstrated responsiveness of these cells to TGF-beta combine to suggest that potentially important interactions may occur between resident glomerular cells and TGF-beta in vivo. Images PMID:2539392

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

    SciTech Connect

    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.

  14. Molecular and Cellular Events Mediating Glomerular Podocyte Dysfunction and Depletion in Diabetes Mellitus

    PubMed Central

    Anil Kumar, P.; Welsh, Gavin I.; Saleem, Moin A.; Menon, Ram K.

    2014-01-01

    The essential function of the kidney is to ensure formation of a relatively protein-free ultra-filtrate, urine. The rate of filtration and composition of the primary renal filtrate is determined by the transport of fluid and solutes across the glomerular filtration barrier consisting of endothelial cells, the glomerular basement membrane, and podocyte foot processes. In diabetes mellitus (DM), components of the kidney that enable renal filtration get structurally altered and functionally compromised resulting in proteinuria that often progresses to end-stage renal disease. Histological alterations in DM include early hypertrophy of glomerular and tubular components, subsequent thickening of basement membrane in glomeruli and tubules, progressive accumulation of extracellular matrix proteins in the glomerular mesangium and loss of podocytes, together constituting a clinical condition referred to as diabetic nephropathy (DN). The glomerulus has become the focus of research investigating the mechanism of proteinuria. In particular, the progressive dysfunction and/or loss of podocytes that is contemporaneous with proteinuria in DN have attracted intense scientific attention. The absolute number of podocytes predicts glomerular function and podocyte injury is a hallmark of various glomerular diseases. This review discusses the importance of podocytes in normal renal filtration and details the molecular and cellular events that lead to podocyte dysfunction and decreased podocyte count in DN. PMID:25309512

  15. The beneficial role of retinoids in glomerular disease.

    PubMed

    Mallipattu, Sandeep K; He, John Cijiang

    2015-01-01

    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 and HIV-associated nephropathy. 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. PMID:25853135

  16. Water Filtration

    ERIC Educational Resources Information Center

    Jacobsen, Erica K.

    2004-01-01

    A water filtration column is devised by students using a two-liter plastic bottle containing gravel, sand, and activated charcoal, to test the filtration potential of the column. Results indicate that the filtration column eliminates many of the contaminating materials, but does not kill bacteria.

  17. Filtration Fundamentals.

    ERIC Educational Resources Information Center

    Ward, Ken; Hunsaker, Scot

    1997-01-01

    Examines how choice of commercial swimming-pool filtration systems is driven by the project-specific needs of the pools. Also highlighted are definitions of specific terms used when discussing filtration systems. Questions that pool designers can answer to make filtration-system purchasing decisions are listed. (GR)

  18. Measuring the intrarenal distribution of glomerular volumes from histological sections.

    PubMed

    Hann, Bradley D; Baldelomar, Edwin J; Charlton, Jennifer R; Bennett, Kevin M

    2016-06-01

    Glomerular volume is an important metric reflecting glomerular filtration surface area within the kidney. Glomerular hypertrophy, or increased glomerular volume, may be an important marker for renal stress. Current stereological techniques report the average glomerular volume (AVglom) within the kidney. These techniques cannot assess the spatial or regional heterogeneity common in developing renal pathology. Here, we report a novel "unfolding" technique to measure the actual distribution of individual glomerular volumes in a kidney from the two-dimensional glomerulus profiles observed by optical microscopy. The unfolding technique was first developed and tested for accuracy with simulations and then applied to measure the number of glomeruli (Nglom), AVglom, and intrarenal distribution of individual glomerular volume (IVglom) in the oligosyndactyl (Os/(+)) mouse model compared with wild-type (WT) controls. The Os/(+) mice had fewer and larger glomeruli than WT mice: Nglom was 12,126 ± 1,658 (glomeruli/kidney) in the WT mice and 5,516 ± 899 in the Os/(+) mice; AVglom was 2.01 ± 0.28 × 10(-4) mm(3) for the WT mice and 3.47 ± 0.35 × 10(-4) mm(3) for the Os/(+) mice. Comparing the glomerular volume distributions in Os/(+) and WT kidneys, we observed that the Os/(+) distribution peaked at a higher value of IVglom than the WT distribution peak, and glomeruli with a radius greater than 55 μm were more prevalent in the Os/(+) mice (3.4 ± 1.6% of total glomeruli vs. 0.6 ± 1.2% in WT). Finally, the largest profiles were more commonly found in the juxtamedullary region. Unfolding is a novel stereological technique that provides a new quantitative view of glomerular volume distribution in the individual kidney. PMID:26984953

  19. Glomerular pathology and the progression of chronic kidney disease.

    PubMed

    Lemley, Kevin V

    2016-06-01

    Structural studies of the glomerulus, largely undertaken in animal models, have informed our understanding of the progression of chronic kidney disease (CKD) for decades. A fundamental tenet of that understanding is that a loss of podocytes underlies progression in many or most cases of progressive CKD. Recent attempts have been made to reconcile earlier findings from glomerular physiology (the primacy of glomerular capillary hypertension in causation of secondary glomerular sclerosis) with structural findings and have suggested a more detailed model of the mechanisms underlying podocyte detachment as viable cells. A new appreciation of the main locus of mechanical challenges to the podocyte (in the filtration slit) may both explain the renoprotective action of some current therapies and help to suggest novel therapeutic strategies. PMID:27122538

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

    SciTech Connect

    Chagnac, A.; Kiberd, B.A.; Farinas, M.C.; Strober, S.; Sibley, R.K.; Hoppe, R.; Myers, B.D. )

    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.

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

    PubMed

    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. PMID:23903370

  2. Glomerular hemodynamics in established glycerol-induced acute renal failure in the rat.

    PubMed Central

    Wolfert, A I; Oken, D E

    1989-01-01

    The glomerular dynamic correlates of failed filtration were studied in volume replete rats with established glycerol-induced acute renal failure (ARF). Over one-half of all nephrons formed virtually no filtrate, while the single nephron glomerular filtration rate (SNGFR) of fluid-filled nephrons, measured at the glomerulotubular junction to preclude the possibility of covert tubular leakage, averaged one-sixth of control (P less than 0.001). Even that low mean value was elevated by a few nephrons with a near normal SNGFR. Renal failure thus reflected both total filtration failure in the majority of nephrons and massively reduced filtration in most of the remainder. Glomerular capillary pressure (Pg) averaged some 14 mmHg below control (P less than 0.001), whereas the arterial colloid osmotic and Bowman's space pressures were not significantly altered. Renocortical and whole kidney blood flow were also unchanged. Marked internephron functional heterogeneity precluded estimates of the ultrafiltration coefficient. However, the fall in SNGFR correlated well with the markedly depressed Pg and afferent net filtration pressure (delta PnetA, P less than 0.001), which in turn were caused by increased preglomerular resistance and a reciprocal fall in efferent arteriolar resistance. This complex change in intrarenal resistances was largely, if not entirely, responsible for failed filtration in this ARF model. PMID:2592568

  3. Septic acute kidney injury: the glomerular arterioles.

    PubMed

    Bellomo, Rinaldo; Wan, Li; Langenberg, Christoph; Ishikawa, Ken; May, Clive N

    2011-01-01

    Acute kidney injury (AKI) is a serious condition that affects many intensive care unit (ICU) patients. The most common causes of AKI in the ICU are severe sepsis and septic shock. The mortality of AKI in septic critically ill patients remains high despite our increasing ability to support vital organs. This is partly due to our poor understanding of the pathogenesis of sepsis-induced renal dysfunction. However, new concepts are emerging to explain the pathogenesis of septic AKI, which challenge previously held dogma. Throughout the past half century, septic AKI has essentially been considered secondary to tubular injury, which, in turn, has been considered secondary to renal ischemia. This belief is curious because the hallmark of septic AKI and AKI in general is the loss of glomerular filtration rate (GFR). It would seem logical, therefore, to focus on the glomerulus in trying to understand why such loss of GFR occurs. Recent experimental observations suggest that, at least in the initial phases of septic AKI, profound changes occur which involve glomerular hemodynamics and lead to loss of GFR. These observations imply that changes in the vasoconstrictor tone of both the afferent and efferent arterioles are an important component of the pathogenesis of septic AKI. PMID:21921614

  4. Glomerular IgG deposition predicts renal outcome in patients with IgA nephropathy.

    PubMed

    Shin, Dong Ho; Lim, Beom Jin; Han, In Mi; Han, Seung Gyu; Kwon, Young Eun; Park, Kyoung Sook; Lee, Mi Jung; Oh, Hyung Jung; Park, Jung Tak; Han, Seung Hyeok; Kang, Shin-Wook; Yoo, Tae-Hyun

    2016-07-01

    Glomerular IgG deposition is frequently observed in patients with IgA nephropathy. However, the association between glomerular IgG deposition and progression of IgA nephropathy is uncertain. Six hundred and twenty-seven patients with biopsy-proven IgA nephropathy were recruited. Histological variables of the Oxford classification (Oxford-MEST) and the presence of glomerular IgG deposits were assessed. Renal progression defined as end-stage renal disease or 50% reduction in estimated glomerular filtration rate was analyzed using Kaplan-Meier methods and Cox regression analysis. Of the study population, 200 patients (31.9%) had glomerular IgG deposition on immunofluorescence staining. During a mean follow-up of 56.8±37.5 months, the rate of renal progression was significantly higher in the IgA nephropathy patients with glomerular IgG deposition compared with the IgA nephropathy patients without glomerular IgG deposition (39.8 vs 12.3 per 1000 patient-years; P<0.001). Of patients with IgG deposition, 178 (28.3%), 20 (3.2%), and 2 (0.3%) patients had mild, moderate, and marked glomerular IgG deposits, receptively. Kaplan-Meier analysis revealed that cumulative renal survival was significantly lower in IgA nephropathy patients with the higher intensity of glomerular IgG deposits (P<0.001). In addition, Cox regression analysis revealed that moderate and marked glomerular IgG deposits significantly predicted renal outcome independent of Oxford-MEST and clinical variables (HR, 2.97; 95% CI, 1.01-8.77; P=0.04). This study showed that that glomerular IgG deposition was independently associated with poor renal outcome in patient with IgA nephropathy. PMID:27102346

  5. Persistent haematuria and proteinuria due to glomerular disease in related Abyssinian cats.

    PubMed

    White, Joanna D; Norris, Jacqueline M; Bosward, Katrina L; Fleay, R; Lauer, Chris; Malik, Richard

    2008-07-01

    Eight cases of glomerular disease in young, related Abyssinian cats are described. Haematuria was the most consistent feature. Six cats developed the nephrotic syndrome. The short-term prognosis was good for cats with haematuria and fair for cats with the nephrotic syndrome as oedema resolved in three of the six cats. Light microscopic examination of renal biopsies from three cats was considered normal or revealed only mild abnormalities. In the three cases subjected to necropsy, histological abnormalities included mild mesangial hypercellularity and adhesions between the glomerular tuft and Bowman's capsule consistent with a focal proliferative glomerulopathy. Further investigation into this glomerulopathy will require ultrastructural and immunohistochemical studies to characterise the glomerular abnormality and genetic analyses to investigate its potential to be an inherited disease. Glomerular disease, potentially a familial one, should be considered in the investigation of persistent haematuria or proteinuria in Abyssinian and related cats. PMID:18455462

  6. Podocyte Pathology and Nephropathy – Sphingolipids in Glomerular Diseases

    PubMed Central

    Merscher, Sandra; Fornoni, Alessia

    2014-01-01

    Sphingolipids are components of the lipid rafts in plasma membranes, which are important for proper function of podocytes, a key element of the glomerular filtration barrier. Research revealed an essential role of sphingolipids and sphingolipid metabolites in glomerular disorders of genetic and non-genetic origin. The discovery that glucocerebrosides accumulate in Gaucher disease in glomerular cells and are associated with clinical proteinuria initiated intensive research into the function of other sphingolipids in glomerular disorders. The accumulation of sphingolipids in other genetic diseases including Tay–Sachs, Sandhoff, Fabry, hereditary inclusion body myopathy 2, Niemann–Pick, and nephrotic syndrome of the Finnish type and its implications with respect to glomerular pathology will be discussed. Similarly, sphingolipid accumulation occurs in glomerular diseases of non-genetic origin including diabetic kidney disease (DKD), HIV-associated nephropathy, focal segmental glomerulosclerosis (FSGS), and lupus nephritis. Sphingomyelin metabolites, such as ceramide, sphingosine, and sphingosine-1-phosphate have also gained tremendous interest. We recently described that sphingomyelin phosphodiesterase acid-like 3b (SMPDL3b) is expressed in podocytes where it modulates acid sphingomyelinase activity and acts as a master modulator of danger signaling. Decreased SMPDL3b expression in post-reperfusion kidney biopsies from transplant recipients with idiopathic FSGS correlates with the recurrence of proteinuria in patients and in experimental models of xenotransplantation. Increased SMPDL3b expression is associated with DKD. The consequences of differential SMPDL3b expression in podocytes in these diseases with respect to their pathogenesis will be discussed. Finally, the role of sphingolipids in the formation of lipid rafts in podocytes and their contribution to the maintenance of a functional slit diaphragm in the glomerulus will be discussed. PMID:25126087

  7. Podocyte pathology and nephropathy - sphingolipids in glomerular diseases.

    PubMed

    Merscher, Sandra; Fornoni, Alessia

    2014-01-01

    Sphingolipids are components of the lipid rafts in plasma membranes, which are important for proper function of podocytes, a key element of the glomerular filtration barrier. Research revealed an essential role of sphingolipids and sphingolipid metabolites in glomerular disorders of genetic and non-genetic origin. The discovery that glucocerebrosides accumulate in Gaucher disease in glomerular cells and are associated with clinical proteinuria initiated intensive research into the function of other sphingolipids in glomerular disorders. The accumulation of sphingolipids in other genetic diseases including Tay-Sachs, Sandhoff, Fabry, hereditary inclusion body myopathy 2, Niemann-Pick, and nephrotic syndrome of the Finnish type and its implications with respect to glomerular pathology will be discussed. Similarly, sphingolipid accumulation occurs in glomerular diseases of non-genetic origin including diabetic kidney disease (DKD), HIV-associated nephropathy, focal segmental glomerulosclerosis (FSGS), and lupus nephritis. Sphingomyelin metabolites, such as ceramide, sphingosine, and sphingosine-1-phosphate have also gained tremendous interest. We recently described that sphingomyelin phosphodiesterase acid-like 3b (SMPDL3b) is expressed in podocytes where it modulates acid sphingomyelinase activity and acts as a master modulator of danger signaling. Decreased SMPDL3b expression in post-reperfusion kidney biopsies from transplant recipients with idiopathic FSGS correlates with the recurrence of proteinuria in patients and in experimental models of xenotransplantation. Increased SMPDL3b expression is associated with DKD. The consequences of differential SMPDL3b expression in podocytes in these diseases with respect to their pathogenesis will be discussed. Finally, the role of sphingolipids in the formation of lipid rafts in podocytes and their contribution to the maintenance of a functional slit diaphragm in the glomerulus will be discussed. PMID:25126087

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

    PubMed

    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. PMID:7289407

  9. Genetic Ablation of Calcium-independent Phospholipase A2γ Induces Glomerular Injury in Mice.

    PubMed

    Elimam, Hanan; Papillon, Joan; Kaufman, Daniel R; Guillemette, Julie; Aoudjit, Lamine; Gross, Richard W; Takano, Tomoko; Cybulsky, Andrey V

    2016-07-01

    Glomerular visceral epithelial cells (podocytes) play a critical role in the maintenance of glomerular permselectivity. Podocyte injury, manifesting as proteinuria, is the cause of many glomerular diseases. We reported previously that calcium-independent phospholipase A2γ (iPLA2γ) is cytoprotective against complement-mediated glomerular epithelial cell injury. Studies in iPLA2γ KO mice have demonstrated an important role for iPLA2γ in mitochondrial lipid turnover, membrane structure, and metabolism. The aim of the present study was to employ iPLA2γ KO mice to better understand the role of iPLA2γ in normal glomerular and podocyte function as well as in glomerular injury. We show that deletion of iPLA2γ did not cause detectable albuminuria; however, it resulted in mitochondrial structural abnormalities and enhanced autophagy in podocytes as well as loss of podocytes in aging KO mice. Moreover, after induction of anti-glomerular basement membrane nephritis in young mice, iPLA2γ KO mice exhibited significantly increased levels of albuminuria, podocyte injury, and loss of podocytes compared with wild type. Thus, iPLA2γ has a protective functional role in the normal glomerulus and in glomerulonephritis. Understanding the role of iPLA2γ in glomerular pathophysiology provides opportunities for the development of novel therapeutic approaches to glomerular injury and proteinuria. PMID:27226532

  10. Glomerular involvement in the arthrogryposis, renal dysfunction and cholestasis syndrome

    PubMed Central

    Holme, Amelia; Hurcombe, Jennifer A.; Straatman-Iwanowska, Anna; Inward, Carol I.; Gissen, Paul; Coward, Richard J.

    2013-01-01

    Background Arthrogryposis, renal dysfunction and cholestasis (ARC) syndrome is a multisystem autosomal-recessive disorder caused by defects in the VPS33B and VIPAR genes, involved in localization of apical membrane proteins. Affected children usually die by 1 year of age, often secondary to infective complications. The classic renal manifestation previously described in ARC syndrome is proximal–tubular dysfunction. The aim of this study is to gain further insight into the renal manifestations of this syndrome. Methods Clinical review of three cases of ARC syndrome presenting to a tertiary centre. Together with measurement of VPS33B and VIPAR protein expression in the human glomerulus. Results The cases demonstrated severe failure to thrive and in addition to commonly described features profound proteinuria and albuminuria, together with hypoalbuminaemia, suggesting glomerular involvement of this syndrome. Western blotting of conditionally immortalized human glomerular cells and ex vivo immunofluorescent analysis of the human glomerulus revealed that VPS33B and VIPAR were highly expressed in glomerular endothelium, and podocytes, but not in the mesangium. Conclusions ARC syndrome affects the glomerulus as well as the proximal tubule in the kidney. Our molecular studies suggest that both cell types that constitute the glomerular filtration barrier are affected in this condition, providing an explanation for the albuminuria that we have observed in our cases. PMID:26019847

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

    PubMed Central

    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

  12. Circadian glomerular function: from physiology to molecular and therapeutical aspects.

    PubMed

    Wuerzner, Grégoire; Firsov, Dmitri; Bonny, Olivier

    2014-08-01

    Life on earth is rhythmic by essence due to day/night alternation, and many biological processes are also cyclic. The kidney has a special role in the organism, controlling electrolytes and water balance, blood pressure, elimination of metabolic waste and xenobiotics and the production of several hormones. The kidney is submitted to changes throughout 24 h with periods of intense activity followed by calmer periods. Filtration, reabsorption and secretion are the three components determining renal function. Here, we review circadian changes related to glomerular function and proteinuria and emphasize the role of the clock in these processes. PMID:24516223

  13. Glomerular disease: looking beyond pathology.

    PubMed

    Wiggins, Roger C; Alpers, Charles E; Holzman, Lawrence B; He, John C; Salant, David J; Chugh, Sumant S; Natarajan, Rama; Trachtman, Howard; Brasile, Lauren; Star, Robert A; Rys-Sikora, Krystyna E; Moxey-Mims, Marva M; Flessner, Michael F

    2014-06-01

    The National Institute of Diabetes and Digestive and Kidney Diseases-supported Kidney Research National Dialogue asked the scientific community to formulate and prioritize research objectives aimed at improved understanding of kidney function and disease progression. Over the past 2 years, 1600 participants posted almost 300 ideas covering all areas of kidney disease. An overriding theme that evolved through these discussions is the need to move beyond pathology to take advantage of basic science and clinical research opportunities to improve diagnostic classification and therapeutic options for people with primary glomerular disease. High-priority research areas included focus on therapeutic targets in glomerular endothelium and podocytes, regenerating podocytes through developmental pathways, use of longitudinal phenotypically defined disease cohorts to improve classification schemes, identifying biomarkers, disease-specific therapeutics, autoantibody triggers, and changing the clinical research culture to promote participation in clinical trials. Together, these objectives provide a path forward for improving clinical outcomes of glomerular disease. PMID:24700796

  14. Glomerular Disease: Looking beyond Pathology

    PubMed Central

    Wiggins, Roger C.; Alpers, Charles E.; Holzman, Lawrence B.; He, John C.; Salant, David J.; Chugh, Sumant S.; Natarajan, Rama; Trachtman, Howard; Brasile, Lauren; Star, Robert A.; Rys-Sikora, Krystyna E.; Moxey-Mims, Marva M.

    2014-01-01

    The National Institute of Diabetes and Digestive and Kidney Diseases–supported Kidney Research National Dialogue asked the scientific community to formulate and prioritize research objectives aimed at improved understanding of kidney function and disease progression. Over the past 2 years, 1600 participants posted almost 300 ideas covering all areas of kidney disease. An overriding theme that evolved through these discussions is the need to move beyond pathology to take advantage of basic science and clinical research opportunities to improve diagnostic classification and therapeutic options for people with primary glomerular disease. High-priority research areas included focus on therapeutic targets in glomerular endothelium and podocytes, regenerating podocytes through developmental pathways, use of longitudinal phenotypically defined disease cohorts to improve classification schemes, identifying biomarkers, disease-specific therapeutics, autoantibody triggers, and changing the clinical research culture to promote participation in clinical trials. Together, these objectives provide a path forward for improving clinical outcomes of glomerular disease. PMID:24700796

  15. Unraveling the immunopathogenesis of glomerular disease.

    PubMed

    Dickinson, Bonny L

    2016-08-01

    Immune-mediated damage to glomerular structures is largely responsible for the pathology associated with the majority of glomerular diseases. Therefore, a detailed understanding of the basic immune mechanisms responsible for glomerular damage is needed to inform the design of novel intervention strategies. Glomerular injury of immune origin is complex and involves both inflammatory and non-inflammatory processes driven by elements of the innate and adaptive immune system. This review summarizes the basic immune mechanisms that cause glomerular injury leading to the nephritic and nephrotic syndromes. A major focus of the review is to highlight the mechanisms by which antibodies cause glomerular injury through their interactions with glomerular cells, complement proteins, phagocytes bearing complement and Fcγ receptors, and dendritic cells expressing the neonatal receptor for IgG, FcRn. PMID:27373970

  16. Nitric oxide synthase in macula densa regulates glomerular capillary pressure.

    PubMed Central

    Wilcox, C S; Welch, W J; Murad, F; Gross, S S; Taylor, G; Levi, R; Schmidt, H H

    1992-01-01

    Tubular-fluid reabsorption by specialized cells of the nephron at the junction of the ascending limb of the loop of Henle and the distal convoluted tubule, termed the macula densa, releases compounds causing vasoconstriction of the adjacent afferent arteriole. Activation of this tubuloglomerular feedback response reduces glomerular capillary pressure of the nephron and, hence, the glomerular filtration rate. The tubuloglomerular feedback response functions in a negative-feedback mode to relate glomerular capillary pressure to tubular-fluid delivery and reabsorption. This system has been implicated in renal autoregulation, renin release, and longterm body fluid and blood-pressure homeostasis. Here we report that arginine-derived nitric oxide, generated in the macula densa, is an additional intercellular signaling molecule that is released during tubular-fluid reabsorption and counters the vasoconstriction of the afferent arteriole. Antibody to rat cerebellar constitutive nitric oxide synthase stained rat macula densa cells specifically. Microperfusion of the macula densa segment of single nephrons with N omega-methyl-L-arginine (an inhibitor of nitric oxide synthase) or with pyocyanin (a lipid-soluble inhibitor of endothelium-derived relaxation factor) showed that generation of nitric oxide can vasodilate the afferent arteriole and increase glomerular capillary pressure; this effect was blocked by drugs that prevent tubular-fluid reabsorption. We conclude that nitric oxide synthase in macula densa cells is activated by tubular-fluid reabsorption and mediates a vasodilating component to the tubuloglomerular feedback response. These findings imply a role for arginine-derived nitric oxide in body fluid-volume and blood-pressure homeostasis, in addition to its established roles in modulation of vascular tone by the endothelium and in neurotransmission. Images PMID:1281548

  17. The effects of PTK787/ZK222584, an inhibitor of VEGFR and PDGFRβ pathways, on intussusceptive angiogenesis and glomerular recovery from Thy1.1 nephritis.

    PubMed

    Wnuk, Monika; Hlushchuk, Ruslan; Tuffin, Gérald; Huynh-Do, Uyen; Djonov, Valentin

    2011-04-01

    The aim of our study was to investigate the phenomenon of intussusceptive angiogenesis with a focus on its molecular regulation by vascular endothelial growth factor receptor (VEGFR)/platelet-derived growth factor receptor β (PDGFRβ) pathways and biological significance for glomerular recovery after acute injury. Glomerular healing by intussusception was examined in a particular setting of Thy1.1 nephritis, where the lysis of mesangial cells results in an initial collapse and successive rebuilding of glomerular capillary structure. Restoration of capillary structure after induction of Thy1.1 nephritis occurred by intussusceptive angiogenesis resulting in i) rapid expansion of the capillary plexus with reinstatement of the glomerular filtration surface and ii) restoration of the archetypical glomerular vascular pattern. Glomerular capillaries of nephritic rats after combined VEGFR2 and PDGFRβ inhibition by PTK787/ZK222584 (PTK/ZK) were tortuous and irregular. However, the onset of intussusceptive angiogenesis was influenced only after long-term PTK/ZK treatment, providing an important insight into differential molecular regulation between sprouting and intussusceptive angiogenesis. PTK/ZK treatment abolished α-smooth muscle actin and tensin expression by injured mesangial cells, impaired glomerular filtration of microspheres, and led to the reduction of glomerular volume and the presence of multiple hemorrhages detectable in the tubular system. Collectively, treatment of nephritic patients with PTK/ZK compound is not recommended. PMID:21435466

  18. Release of glomerular heparan-/sup 35/SO/sub 4/ proteoglycan by heparin from glomeruli of streptozocin-induced diabetic rats

    SciTech Connect

    Klein, D.J.; Oegema, T.R. Jr.; Brown, D.M.

    1989-01-01

    Abnormalities in the incorporation of heparan sulfate proteoglycan into the glomerular basement membrane have been implicated in the pathogenesis of various proteinuric states, including diabetes mellitus. To understand further the interactions between proteoglycans and glomerular extracellular matrices, glomeruli were isolated from normal and streptozocin-induced diabetic rats after in vivo exposure to 35S-labeled sulfate and were treated with heparin in vitro. Heparin treatment released a unique heparan sulfate proteoglycan from glomerular cell surface or extracellular matrix proteoglycan receptors. Another, smaller heparan sulfate proteoglycan was the most abundant proteoglycan released into medium and was released constitutively in medium with or without added heparin. While the two heparin-extracted proteoglycans copurified on anion-exchange and gel-filtration chromatographic columns, they were resolved by composite 0.6% agarose--1.8% polyacrylamide gel electrophoresis. Glomeruli from diabetic rats contained decreased proportions of the heparin-releasable heparan sulfate proteoglycan and more constitutively released heparan sulfate proteoglycan. The apparent molecular weight and intrinsic charge of the heparin-released proteoglycan mixture and the apparent molecular weight and sulfation pattern of their 35S-labeled glycosaminoglycan chains after nitrous acid deaminative cleavage were similar in the two groups. A brief trypsin digestion of heparin-treated glomeruli released proportionately less integral membrane and extracellular matrix 35S-labeled proteoglycans and 35S-labeled glycopeptides from diabetic glomeruli than form control glomeruli. Elution of these 35S-labeled macromolecules from anion-exchange columns and migration in agarose-polyacrylamide gels were similar in the two groups.

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

    PubMed

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

    2012-05-01

    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. PMID:22349487

  20. Cytoplasmic Calcium in the Mediation of Macula Densa Tubulo-Glomerular Feedback Responses

    NASA Astrophysics Data System (ADS)

    Darwin Bell, P.; Navar, L. Gabriel

    1982-02-01

    Within each nephron of the mammalian kidney, a feedback mechanism operating between the macula densa segment of the distal tubule and the afferent arteriole participates in the regulation of glomerular filtration rate. Retrograde microperfusion studies in rats were conducted to test the hypothesis that activation of macula densa cytoplasmic calcium is involved in the transmission of feedback signals to the vascular elements. Perfusion into distal tubules with a hypotonic solution (70 milliosmolar) elicited moderate decreases in glomerular pressure of 6 ± 0.8 millimeters of mercury. With the addition of a calcium ionophore (A23187) glomerular pressure decreased by 16 ± 1.1 millimeters of mercury. When a solution devoid of calcium but containing A23187 was used, the feedback response was inhibited. Thus, cytoplasmic calcium within the receptor cells may participate in the transmission of feedback signals to the contractile cells.

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

    PubMed Central

    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

  2. The podocyte as a direct target for treatment of glomerular disease?

    PubMed

    Mallipattu, Sandeep K; He, John C

    2016-07-01

    The Centers for Disease Control and Prevention estimates more than 10% of adults in the United States, over 20 million Americans, have chronic kidney disease (CKD). A failure to maintain the glomerular filtration barrier directly contributes to the onset of CKD. The visceral epithelial cells, podocytes, are integral to the maintenance of this renal filtration barrier. Direct podocyte injury contributes to the onset and progression of glomerular diseases such as minimal change disease (MCD), focal segmental glomerular sclerosis (FSGS), diabetic nephropathy, and HIV-associated nephropathy (HIVAN). Since podocytes are terminally differentiated with minimal capacity to self-replicate, they are extremely sensitive to cellular injury. In the past two decades, our understanding of the mechanism(s) by which podocyte injury occurs has greatly expanded. With this newfound knowledge, therapeutic strategies have shifted to identifying targets directed specifically at the podocyte. Although the systemic effects of these agents are important, their direct effect on the podocyte proves to be essential in ameliorating glomerular disease. In this review, we highlight the mechanisms by which these agents directly target the podocyte independent of its systemic effects. PMID:27097894

  3. Rituximab in immunologic glomerular diseases

    PubMed Central

    Ejaz, A Ahsan; Asmar, Abdo; Alsabbagh, Mourad M

    2012-01-01

    Experimental data suggest that the B-cell antigen CD20 may play a significant role in the pathogenesis of many diseases including glomerular diseases. These and other findings underpin the central concept of B-cell-depleting therapies that target CD20 antigen as treatments for lupus nephritis, idiopathic membranous nephropathy, focal segmental glomerulosclerosis, cryglobulinemic glomerulonephritis, antibody mediated renal allograft rejection and recurrent glomerulonephritis in renal allograft. Use of rituximab as a B-cell depleting therapy has been associated with clinical improvement and has emerged as a possible adjunct or alternative treatment option in this field of nephrology. PMID:22377738

  4. [Renal abnormalities in HIV infected patients].

    PubMed

    Pernasetti, María Marta; Chiurchiu, Carlos; Fuente, Jorge de la; Arteaga, Javier de; Douthat, Walter; Bardosy, Cecilia; Zarate, Abel; Massari, Pablo U

    2010-01-01

    Several renal complications may occur during HIV infection, especially in advanced stages related to HIV, to other infectious agents and/or drugs. Little is known about the prevalence of renal diseases that may occur as a complication of or related to HIV infection in asymptomatic patients. This is a single center cross-sectional study of asymptomatic HIV(+) patients referred to a nefrology care service at an Argentine hospital to look for the presence of renal abnormalities. Fifty two consecutive patients were studied between April and November 2008. Patients underwent plasma and urine analysis, ultrasound, and kidney biopsy as needed. Mean age was 39.9 +/- 10.6 years, 88% were male, time from HIV diagnosis 53.2 +/- 41.2 months (2-127); 71% had HIV-disease and 77% were on antiretroviral therapy. Mean plasma HIV-RNA copies number was 7.043 +/- 3.322 and CD4+ cell count: 484 +/- 39. Pathologic findings in urine analysis were present in 30.7% of patients: albuminuria 16.6%, microscopic hematuria 11.5%, hypercalciuria 10.8% and crystalluria 6%. Mean glomerular filtration rate was 102.2 +/- 22.95 ml/min (34-149) and 41% of patients could be classified in stages 1 to 3 of chronic kidney disease. Renal abnormalities prevaled in older patients without relationship with presence of HIV-disease. Two patients were biopsied and the findings included: tubulointerstitial nephritis with presence of crystal deposition in one and IgA nephropathy in the other. No HIV-associated nephropathy was detected. The broad spectrum and the high prevalence of lesions found in this series suggest that asymptomatic HIV-infected patients should routinely undergo renal evaluation. PMID:20529774

  5. Genetic Analysis of Intracapillary Glomerular Lipoprotein Deposits in Aging Mice

    PubMed Central

    Noordmans, Gerda A.; Huang, Yuan; Savage, Holly; van Dijk, Marcory C. R. F.; Schaart, Gert; van den Bergh Weerman, Marius A.; Heeringa, Peter; Hillebrands, Jan-Luuk; Korstanje, Ron; van Goor, Harry

    2014-01-01

    Background 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. Methods 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. Results 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. Conclusions 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. PMID:25353171

  6. Effects of Therapy on Urine Neutrophil Gelatinase-Associated Lipocalin in Nondiabetic Glomerular Diseases with Proteinuria

    PubMed Central

    Vanavanan, Somlak; Chittamma, Anchalee; Phakdeekitcharoen, Bunyong; Lertrit, Amornpan; Sathirapongsasuti, Nuankanya

    2016-01-01

    Urine neutrophil gelatinase-associated lipocalin (NGAL) is widely used as a biomarker for acute kidney injury. Cross-sectional studies have shown that NGAL may be elevated in glomerular diseases, but there is limited information on the value of NGAL in predicting treatment response or on the changes of NGAL levels after therapy. We prospectively evaluated the effects of therapy on NGAL in nondiabetic glomerular diseases. Urine NGAL was collected at biopsy and follow-up at 12 months. At baseline, NGAL in glomerular disease patients (n = 43) correlated with proteinuria, but not with glomerular filtration rate (GFR). After therapy with renin-angiotensin blockers and/or immune modulating agents, change of NGAL correlated with change of proteinuria, but not with change of GFR. NGAL at baseline was not different between patients in complete remission (CR) at follow-up compared to those not in remission (NR). Compared to baseline, NGAL at follow-up decreased in CR (n = 10), but not in NR. Change of NGAL was greater in CR than NR. In conclusion, the change of urine NGAL correlated with the change of proteinuria. Baseline NGAL was not a predictor of complete remission. Future studies will be necessary to determine the role of NGAL as a predictor of long term outcome in proteinuric glomerular diseases. PMID:27525120

  7. Effect of Acetazolamide on Obesity-Induced Glomerular Hyperfiltration: A Randomized Controlled Trial

    PubMed Central

    Erman, Arie; Bar Sheshet Itach, Sarit; Ori, Yaacov; Rozen-Zvi, Benaya; Gafter, Uzi; Chagnac, Avry

    2015-01-01

    Aims Obesity is an important risk factor for the development of chronic kidney disease. One of the major factors involved in the pathogenesis of obesity-associated kidney disease is glomerular hyperfiltration. Increasing salt-delivery to the macula densa is expected to decrease glomerular filtration rate (GFR) by activating tubuloglomerular feedback. Acetazolamide, a carbonic anhydrase inhibitor which inhibits salt reabsorption in the proximal tubule, increases distal salt delivery. Its effects on obesity-related glomerular hyperfiltration have not previously been studied. The aim of this investigation was to evaluate whether administration of acetazolamide to obese non diabetic subjects reduces glomerular hyperfiltration. Materials and Methods The study was performed using a randomized double-blind crossover design. Obese non-diabetic men with glomerular hyperfiltration were randomized to receive intravenously either acetazolamide or furosemide at equipotent doses. Twelve subjects received the allocated medications. Two weeks later, the same subjects received the drug which they had not received during the first study. Inulin clearance, p-aminohippuric acid clearance and fractional lithium excretion were measured before and after medications administration. The primary end point was a decrease in GFR, measured as inulin clearance. Results GFR decreased by 21% following acetazolamide and did not decrease following furosemide. Renal vascular resistance increased by 12% following acetazolamide, while it remained unchanged following furosemide administration. Natriuresis increased similarly following acetazolamide and furosemide administration. Sodium balance was similar in both groups. Conclusions Intravenous acetazolamide decreased GFR in obese non-diabetic men with glomerular hyperfiltration. Furosemide, administered at equipotent dose, did not affect GFR, suggesting that acetazolamide reduced glomerular hyperfiltration by activating tubuloglomerular feedback

  8. Abdominal Adipose Tissue was Associated with Glomerular Hyperfiltration among Non- Diabetic and Normotensive Adults with a Normal Body Mass Index.

    PubMed

    Lee, Jeonghwan; Kim, Hye Jin; Cho, Belong; Park, Jin Ho; Choi, Ho Chun; Lee, Cheol Min; Oh, Seung Won; Kwon, Hyuktae; Heo, Nam Ju

    2015-01-01

    Glomerular hyperfiltration is recognized as an early marker of progressive kidney dysfunction in the obese population. This study aimed to identify the relationship between glomerular hyperfiltration and body fat distribution measured by computed tomography (CT) in healthy Korean adults. The study population included individuals aged 20-64 years who went a routine health check-up including an abdominal CT scan. We selected 4,378 individuals without diabetes and hypertension. Glomerular filtration rate was estimated using the CKD-EPI equation, and glomerular hyperfiltration was defined as the highest quintile of glomerular filtration rate. Abdominal adipose tissue areas were measured at the level of the umbilicus using a 16-detector CT scanner, and the cross-sectional area was calculated using Rapidia 2.8 CT software. The prevalence of glomerular hyperfiltration increased significantly according to the subcutaneous adipose tissue area in men (OR = 1.74 (1.16-2.61), P for trend 0.016, for the comparisons of lowest vs. highest quartile) and visceral adipose tissue area in women (OR = 2.34 (1.46-3.75), P for trend < 0.001) in multivariate analysis. After stratification by body mass index (normal < 23 kg/m2, overweight ≥ 23 kg/m2), male subjects with greater subcutaneous adipose tissue, even those in the normal BMI group, had a higher prevalence of glomerular hyperfiltration (OR = 2.11 (1.17-3.80), P for trend = 0.009). Among women, the significance of visceral adipose tissue area on glomerular hyperfiltration resulted from the normal BMI group (OR = 2.14 (1.31-3.49), P for trend = 0.002). After menopause, the odds ratio of the association of glomerular hyperfiltration with subcutaneous abdominal adipose tissue increased (OR = 2.96 (1.21-7.25), P for trend = 0.013). Subcutaneous adipose tissue areas and visceral adipose tissue areas are positively associated with glomerular hyperfiltration in healthy Korean adult men and women, respectively. In post-menopausal women

  9. Glomerular hemodynamic alterations during acute hyperinsulinemia in normal and diabetic rats

    NASA Technical Reports Server (NTRS)

    Tucker, B. J.; Anderson, C. M.; Thies, R. S.; Collins, R. C.; Blantz, R. C.

    1992-01-01

    Treatment of insulin dependent diabetes invariably requires exogenous insulin to control blood glucose. Insulin treatment, independent of other factors associated with insulin dependent diabetes, may induce changes that affect glomerular function. Due to exogenous delivery of insulin in insulin dependent diabetes entering systemic circulation prior to the portal vein, plasma levels of insulin are often in excess of that observed in non-diabetics. The specific effects of hyperinsulinemia on glomerular hemodynamics have not been previously examined. Micropuncture studies were performed in control (non-diabetic), untreated diabetic and insulin-treated diabetic rats 7 to 10 days after administration of 65 mg/kg body weight streptozotocin. After the first period micropuncture measurements were obtained, 5 U of regular insulin (Humulin-R) was infused i.v., and glucose clamped at euglycemic values (80 to 120 mg/dl). Blood glucose concentration in non-diabetic controls was 99 +/- 6 mg/dl. In control rats, insulin infusion and glucose clamp increased nephron filtration rate due to decreases in both afferent and efferent arteriolar resistance (afferent greater than efferent) resulting in increased plasma flow and increased glomerular hydrostatic pressure gradient. However, insulin infusion and glucose clamp produced the opposite effect in both untreated and insulin-treated diabetic rats with afferent arteriolar vasoconstriction resulting in decreases in plasma flow, glomerular hydrostatic pressure gradient and nephron filtration rate. Thromboxane A2 (TX) synthetase inhibition partially decreased the vasoconstrictive response due to acute insulin infusion in diabetic rats preventing the decrease in nephron filtration rate.(ABSTRACT TRUNCATED AT 250 WORDS).

  10. Rotary filtration system

    DOEpatents

    Herman, David T.; Maxwell, David N.

    2011-04-19

    A rotary filtration apparatus for filtering a feed fluid into permeate is provided. The rotary filtration apparatus includes a container that has a feed fluid inlet. A shaft is at least partially disposed in the container and has a passageway for the transport of permeate. A disk stack made of a plurality of filtration disks is mounted onto the shaft so that rotation of the shaft causes rotation of the filtration disks. The filtration disks may be made of steel components and may be welded together. The shaft may penetrate a filtering section of the container at a single location. The rotary filtration apparatus may also incorporate a bellows seal to prevent leakage along the shaft, and an around the shaft union rotary joint to allow for removal of permeate. Various components of the rotary filtration apparatus may be removed as a single assembly.

  11. Glomerular injury is exacerbated in diabetic integrin alpha1-null mice.

    PubMed

    Zent, R; Yan, X; Su, Y; Hudson, B G; Borza, D-B; Moeckel, G W; Qi, Z; Sado, Y; Breyer, M D; Voziyan, P; Pozzi, A

    2006-08-01

    Excessive glomerular collagen IV and reactive oxygen species (ROS) production are key factors in the development of diabetic nephropathy. Integrin alpha1beta1, the major collagen IV receptor, dowregulates collagen IV and ROS production, suggesting this integrin might determine the severity of diabetic nephropathy. To test this possibility, wild-type and integrin alpha1-null mice were rendered diabetic with streptozotocin (STZ) (100 mg/kg single intraperitoneal injection), after which glomerular filtration rate (GFR), glomerular collagen deposition, and glomerular basement membrane (GBM) thickening were evaluated. In addition, ROS and collagen IV production by mesangial cells as well as their proliferation was measured in vitro. Diabetic alpha1-null mice developed worse renal disease than diabetic wild-type mice. A significant increase in GFR was evident in the alpha1-null mice at 6 weeks after the STZ injection; it started to decrease by week 24 and reached levels of non-diabetic mice by week 36. In contrast, GFR only increased in wild-type mice at week 12 and its elevation persisted throughout the study. Diabetic mutant mice also showed increased glomerular deposition of collagen IV and GBM thickening compared to diabetic wild-type mice. Primary alpha1-null mesangial cells exposed to high glucose produced more ROS than wild-type cells, which led to decreased proliferation and increased collagen IV synthesis, thus mimicking the in vivo finding. In conclusion, this study suggests that lack of integrin alpha1beta1 exacerbates the glomerular injury in a mouse model of diabetes by modulating GFR, ROS production, cell proliferation, and collagen deposition. PMID:16775606

  12. Direct effects of platelet-activating factor on glomerular capillary permeability.

    PubMed

    Sharma, R; Sharma, M; Li, J Z; McCarthy, E T; Savin, V J

    1997-01-01

    Platelet-activating factor (PAF) is an important mediator of injury in acute renal failure and glomerulonephritis. Intrarenal infusion of PAF reduces glomerular filtration rate and renal plasma flow and increases glomerular permselectivity via its renal hemodynamic and/or immunologic effects. Direct effects of PAF on glomerular capillary permeability are not known. We studied the direct effects of PAF on mesangial contraction (a measure of filtration area), glomerular capillary hydraulic conductivity (L[p]) and capillary albumin permeability (P[albumin]). Glomeruli were isolated from Sprague-Dawley rats and incubated with or without various concentrations of PAF (10[-9], 10[-7] and 10[-5] M) for up to 5 h at 37 degrees C. Mesangial contraction (percent change in glomerular volume) was assessed from the gradual decrease in volume of glomeruli during 20 min of incubation with PAF. L(p) was calculated from the rate of change in glomerular volume during the 0.1 s of capillary expansion in response to a transcapillary oncotic gradient. P(albumin) was calculated from a change in relative volume of glomeruli in response to an oncotic gradient. Mesangial contraction was maximal after 20 min of incubation and was concentration dependent (5.2+/-0.9, 7.9+/-1.0 and 10.0+/-1.0%, respectively, with PAF 10(-9), 10(-7) and 10(-5) M). Incubation of glomeruli with PAF 10(-7) M for 60 min at 37 degrees C caused a significant decrease in L(p) (2.25+/-0.30 vs. control 3.12+/-0.28 microl x min(-1) x mm Hg(-1) x cm(-1), n = 5). P(albumin) of glomeruli incubated with PAF was unchanged up to 2 h but increased significantly with the highest concentration of PAF (10(-5) M) after 3 h of incubation (0.60+/-0.18, n=15, vs. control 0.00+/-0.08, n = 20), whereas lower concentrations of PAF (10[-7] or 10[-9] M) required at least 5 h of incubation with glomeruli to cause a significant increase in P(albumin) (0.45+/-0.09 and 0.48+/-0.07, respectively, n=15, vs. control 0.00+/-0.08, n=15). We

  13. Dynamics of Glomerular Ultrafiltration in the Rat. IV. DETERMINATION OF THE ULTRAFILTRATION COEFFICIENT

    PubMed Central

    Deen, William M.; Troy, Julia L.; Robertson, Channing R.; Brenner, Barry M.

    1973-01-01

    Pressures and flow rates were measured in accessible surface glomeruli of mutant Wistar rats under conditions deliberately designed to prevent achievement of filtration pressure equilibrium, that is, the equalization of transcapillary hydrostatic and oncotic pressures by the efferent end of the glomerulus as typically observed in the normal hydropenic rat. Disequilibrium was obtained at elevated levels of glomerular plasma flow (GPF) brought about by acute expansion of plasma volume with a volume of rat plasma equal to 5% of body weight. Glomerular hydrostatic and oncotic pressures measured at high GPF were used to calculate the ultrafiltration coefficient, Kf, the product of effective hydraulic permeability and surface area. GPF was then either lowered (by aortic constriction) or raised (by carotid occlusion) in order to examine the dependence of Kf on GPF. The value of Kf per glomerulus, 0.08 nl/(s·mm Hg), was found not to vary over an approximately twofold range of GPF. This finding, taken together with data from previous studies from this laboratory, leads us to conclude that plasma-flow dependence of glomerular filtration rate (GFR) results primarily from flow-induced changes in mean ultrafiltration pressure, rather than large changes in Kf. PMID:4703234

  14. Ernest Henry Starling (1866-1927) on the glomerular and tubular functions of the kidney.

    PubMed

    Fine, Leon G

    2014-01-01

    Around the turn of the 20th century, Ernest Henry Starling (1866-1927) made many fundamental contributions to the understanding of human physiology. With a deep interest in how fluid balance is regulated, he naturally turned to explore the intricacies of kidney function. Early in his career he focused upon the process of glomerular filtration and was able to substantiate the view of Carl Ludwig that this process can be explained entirely upon the basis of hydrostatic and oncotic pressure gradients across the glomerular capillary wall and that the process can be regulated by alterations in the tone of the afferent and efferent arterioles. To explore renal tubular function he employed a heart-lung-kidney model in the dog and was able to infer that certain substances are reabsorbed by the tubules (e.g. sodium chloride) and certain by tubular secretion (e.g. uric acid, indigo carmine dye). By temporarily blocking tubular function using hydrocyanic acid he was able to conclude that secreted substances must be taken up on the peritubular side of the cell and concentrated within the cell to drive the secretory process. Finally, he was able to appreciate that the kidney is an organ which is regulated according to the needs of the organism and that the processes of glomerular filtration, tubular secretion and reabsorption are all subject to regulatory influences, which have evolved to conserve the normal chemical composition of the cells and fluids of the body. PMID:24970544

  15. Anti-glomerular basement membrane blood test

    MedlinePlus

    GBM antibody test; Antibody to human glomerular basement membrane; Anti-GBM antibodies ... Normally, there are none of these antibodies in the blood. Normal ... labs use different measurements or test different samples. Talk ...

  16. Is Abnormal Urine Protein/Osmolality Ratio Associated with Abnormal Renal Function in Patients Receiving Tenofovir Disoproxil Fumarate?

    PubMed Central

    Marcelin, Jasmine R.; Berg, Melody L.; Tan, Eugene M.; Amer, Hatem; Cummins, Nathan W.; Rizza, Stacey A.

    2016-01-01

    Background Risk factors for and optimal surveillance of renal dysfunction in patients on tenofovir disoproxil fumarate (TDF) remain unclear. We investigated whether a urine protein-osmolality (P/O) ratio would be associated with renal dysfunction in HIV-infected persons on TDF. Methods This retrospective, single-center study investigated the relationship between parameters of renal function (estimated glomerular filtration rate (eGFR) and P/O-ratio) and risk factors for development of kidney dysfunction. Subjects were HIV-infected adults receiving TDF with at least one urinalysis and serum creatinine performed between 2010 and 2013. Regression analyses were used to analyze risk factors associated with abnormal P/O-ratio and abnormal eGFR during TDF therapy. Results Patients were predominately male (81%); (65%) were Caucasian. Mean age was 45.1(±11.8) years; median [IQR] TDF duration was 3.3 years. [1.5–7.6]. Median CD4+ T cell count and HIV viral load were 451 cells/μL [267.5–721.5] and 62 copies/mL [0–40,150], respectively. Abnormal P/O-ratio was not associated with low eGFR. 68% of subjects had an abnormal P/O-ratio and 9% had low eGFR. Duration of TDF use, age, diabetes and hypertension were associated with renal dysfunction in this study. After adjustment for age, subjects on TDF > 5 years had almost a four-fold increased likelihood of having an abnormal P/O-ratio than subjects on TDF for < 1yr (OR 3.9; 95% CI 1.2–14.0; p = 0.024). Conclusion Abnormal P/O-ratio is common in HIV-infected patients on TDF but was not significantly associated with low eGFR, suggesting that abnormal P/O-ratio may be a very early biomarker of decreased renal function in HIV infected patients. PMID:26872144

  17. Atubular glomeruli and glomerulotubular junction abnormalities in diabetic nephropathy.

    PubMed

    Najafian, Behzad; Kim, Youngki; Crosson, John T; Mauer, Michael

    2003-04-01

    Atubular glomeruli (AG) have been described in several renal disorders. However, little attention has been paid to AG in diabetic nephropathy (DN). Preliminary studies suggested that tip lesions were frequently present in type 1 diabetic (D) patients with proteinuria. The aim of this study was to determine the frequency of AG and their possible relationship with tip lesions in DN. Renal biopsies from eight proteinuric type 1 D patients with normal to moderately reduced GFR (76 +/- 26 ml/min per 1.73 m(2)) and eight normal subjects were studied by light (LM) and electron microscopy (EM). Glomerular volume, volume of the glomerular corpuscle, which is tuft, and the fractional volumes of proximal, distal, and atrophic tubules per cortex were estimated using appropriate stereologic methods. Glomerulotubular junctions were examined on serial sections and classified into glomeruli attached to: normal tubules (NT); short atrophic tubules (SAT); long atrophic tubules (LAT); atrophic tubules with no observable glomerular opening (ATNO); and atubular glomeruli (AG). EM studies showed typical diabetic changes in biopsies, including increased GBM width (P < 0.00001) and mesangial fractional volume (P < 0.0001) and decreased filtration surface density (P < 0.01) compared with normal subjects. Seventeen percent of glomeruli in the D patients were atubular, and 51% were attached to atrophic tubules. Tip lesions were present in all SAT, 64% of LAT, 82% of ATNO, and only 9% of NT and were never observed in normal subjects. The relative volume of AG was smaller than glomeruli in other categories (P < 0.05). Fractional volume of proximal (P < 0.01) and distal (P <0.01) tubules per cortex were decreased, while fractional volume of cortical interstitium (P <0.00001) and atrophic tubules (P <0.01) were increased in D patients. Fractional volume of atrophic tubules, %AG, and percent of glomeruli with tip lesion explained 94% of the GFR variability in diabetic patients (P <0.05). Thus, AG

  18. WATER FILTRATION AT DULUTH

    EPA Science Inventory

    After partial completion of the Lakewood Filtration Plant at Duluth, studies were begun with funding provided by the demonstration grant. Research covered a variety of topics and was done with a 10 gpm pilot plant located at the filtration plant, with the full scale plant operati...

  19. 7. OBLIQUE INTERIOR VIEW OF FILTRATION ROOM IN FILTRATION PLANT ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    7. OBLIQUE INTERIOR VIEW OF FILTRATION ROOM IN FILTRATION PLANT (#1773), LOOKING NORTHEAST, SHOWING PUMP NO. 1 AND METERING EQUIPMENT - Presidio Water Treatment Plant, Filtration Plant, East of Lobos Creek at Baker Beach, San Francisco, San Francisco County, CA

  20. 8. OBLIQUE INTERIOR VIEW OF FILTRATION ROOM IN FILTRATION PLANT ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    8. OBLIQUE INTERIOR VIEW OF FILTRATION ROOM IN FILTRATION PLANT (#1773), LOOKING SOUTHWEST, SHOWING MEZZANINE WITH FILTER TANKS AT REAR - Presidio Water Treatment Plant, Filtration Plant, East of Lobos Creek at Baker Beach, San Francisco, San Francisco County, CA

  1. Quantifying Glomerular Permeability of Fluorescent Macromolecules Using 2-Photon Microscopy in Munich Wistar Rats

    PubMed Central

    Sandoval, Ruben M.; Molitoris, Bruce A.

    2013-01-01

    Kidney diseases involving urinary loss of large essential macromolecules, such as serum albumin, have long been thought to be caused by alterations in the permeability barrier comprised of podocytes, vascular endothelial cells, and a basement membrane working in unison. Data from our laboratory using intravital 2-photon microscopy revealed a more permeable glomerular filtration barrier (GFB) than previously thought under physiologic conditions, with retrieval of filtered albumin occurring in an early subset of cells called proximal tubule cells (PTC)1,2,3. Previous techniques used to study renal filtration and establishing the characteristic of the filtration barrier involved micropuncture of the lumen of these early tubular segments with sampling of the fluid content and analysis4. These studies determined albumin concentration in the luminal fluid to be virtually non-existent; corresponding closely to what is normally detected in the urine. However, characterization of dextran polymers with defined sizes by this technique revealed those of a size similar to serum albumin had higher levels in the tubular lumen and urine; suggesting increased permeability5. Herein is a detailed outline of the technique used to directly visualize and quantify glomerular fluorescent albumin permeability in vivo. This method allows for detection of filtered albumin across the filtration barrier into Bowman's space (the initial chamber of urinary filtration); and also allows quantification of albumin reabsorption by proximal tubules and visualization of subsequent albumin transcytosis6. The absence of fluorescent albumin along later tubular segments en route to the bladder highlights the efficiency of the retrieval pathway in the earlier proximal tubule segments. Moreover, when this technique was applied to determine permeability of dextrans having a similar size to albumin virtually identical permeability values were reported2. These observations directly support the need to expand

  2. Measuring glomerular number from kidney MRI images

    NASA Astrophysics Data System (ADS)

    Thiagarajan, Jayaraman J.; Natesan Ramamurthy, Karthikeyan; Kanberoglu, Berkay; Frakes, David; Bennett, Kevin; Spanias, Andreas

    2016-03-01

    Measuring the glomerular number in the entire, intact kidney using non-destructive techniques is of immense importance in studying several renal and systemic diseases. Commonly used approaches either require destruction of the entire kidney or perform extrapolation from measurements obtained from a few isolated sections. A recent magnetic resonance imaging (MRI) method, based on the injection of a contrast agent (cationic ferritin), has been used to effectively identify glomerular regions in the kidney. In this work, we propose a robust, accurate, and low-complexity method for estimating the number of glomeruli from such kidney MRI images. The proposed technique has a training phase and a low-complexity testing phase. In the training phase, organ segmentation is performed on a few expert-marked training images, and glomerular and non-glomerular image patches are extracted. Using non-local sparse coding to compute similarity and dissimilarity graphs between the patches, the subspace in which the glomerular regions can be discriminated from the rest are estimated. For novel test images, the image patches extracted after pre-processing are embedded using the discriminative subspace projections. The testing phase is of low computational complexity since it involves only matrix multiplications, clustering, and simple morphological operations. Preliminary results with MRI data obtained from five kidneys of rats show that the proposed non-invasive, low-complexity approach performs comparably to conventional approaches such as acid maceration and stereology.

  3. Leveraging melanocortin pathways to treat glomerular diseases

    PubMed Central

    Gong, Rujun

    2013-01-01

    The melanocortin system is a neuroimmunoendocrine hormone system that constitutes the fulcrum in the homeostatic control of a diverse array of physiological functions, including melanogenesis, inflammation, immunomodulation, adrenocortical steroidogenesis, hemodynamics, natriuresis, energy homeostasis, sexual function and exocrine secretion. The kidney is a quintessential effector organ of the melanocortin hormone system with melanocortin receptors abundantly expressed by multiple renal paranchymal cells, including podocytes, mesangial cells, glomerular endothelial cells and renal tubular cells. Converging evidence unequivocally demonstrates that the melanocortin based therapy by using the melanocortin peptide adrenocorticotropic hormone (ACTH) is prominently effective in inducing remission of steroid resistant nephrotic syndrome caused by a variety of glomerular diseases, including membranous nephropathy and podocytopathies such as minimal change disease and focal segmental glomerulosclerosis, suggesting a steroidogenic independent melanocortin mechanism. Mechanistically, ACTH and other melanocortin peptides as well as synthetic melanocortin analogues possess potent proteinuria reducing and renoprotective effects that could be attributable to both direct protection of glomerular cells and systemic immunomodulation. Thus, leveraging melanocortin signaling pathways by using either the existing U.S. Food and Drug Administration approved melanocorin peptide ACTH or novel synthetic melanocortin analogues represents a promising and pragmatic therapeutic strategy for glomerular diseases. This review article introduces the biophysiology of melanocortin hormone system with emphasis on the kidney as the target organ, discusses the existing clinical and experimental data on melanocortin treatments for glomerular diseases, elucidates the potential mechanisms of action, and describes the potential side effects of melanocortin based therapy. PMID:24602463

  4. Acute hyperglycemia induces rapid, reversible increases in glomerular permeability in nondiabetic rats.

    PubMed

    Axelsson, Josefin; Rippe, Anna; Rippe, Bengt

    2010-06-01

    This study was performed to investigate the impact of acute hyperglycemia (HG) on the permeability of the normal glomerular filtration barrier in vivo. In anesthetized Wistar rats (250-280 g), the left ureter was catheterized for urine collection, while simultaneously blood access was achieved. Rats received an intravenous (iv) infusion of either 1) hypertonic glucose to maintain blood glucose at 20-25 mM (G; n = 8); 2) hypertonic glucose as in 1) and a RhoA-kinase inhibitor (Y-27632; Rho-G; n = 8); 3) 20% mannitol (MANN; n = 7) or 4) hypertonic (12%) NaCl to maintain plasma crystalloid osmotic pressure (pi(cry)) at approximately 320-325 mosmol/l (NaCl; n = 8) or 5) physiological saline (SHAM; n = 8). FITC-Ficoll 70/400 was infused iv for at least 20 min before termination of the experiments, and plasma and urine were collected to determine the glomerular sieving coefficients (theta) for polydisperse Ficoll (molecular radius 15-80 A) by high-performance size-exclusion chromatography. In G there was a marked increase in for Ficoll(55-80A) at 20 min, which was completely reversible within 60 min and abrogated by a Rho-kinase (ROCK) inhibitor, while glomerular permeability remained unchanged in MANN and NaCl. In conclusion, acute HG caused rapid, reversible increases in for large Ficolls, not related to the concomitant hyperosmolarity, but sensitive to ROCK inhibition. The changes observed were consistent with the formation of an increased number of large pores in the glomerular filter. The sensitivity of the permeability changes to ROCK inhibition strongly indicates that the cytoskeleton of the cells in the glomerular barrier may be involved in these alterations. PMID:20237233

  5. Urine synaptopodin excretion is an important marker of glomerular disease progression

    PubMed Central

    Kwon, Soon Kil; Kim, Seung Jung; Kim, Hye-Young

    2016-01-01

    Background/Aims: Podocytes play an important role in maintaining the glomerular filtration barrier and in formation of the slit diaphragm. Podocyte loss is associated with chronic kidney disease progression, but it is not clear whether urinary podocyte proteins in urine reflect the clinical extent of glomerular damage. We investigated the correlation between the amounts of urinary podocyte proteins and renal function and albuminuria. Methods: The study enrolled 33 patients with diabetic kidney disease or glomerular disease and measured urinary podocytes proteins using Western blotting. Urinary podocyte proteins were measured according to the density of the bands on Western blotting. We measured serum creatinine and the spot urine albumin/creatinine ratio as markers of renal damage, and compared the correlation of urinary podocyte protein in the glomerular disease patients. Results: The mean patient age was 49.3 ± 16.5 years, the mean serum creatinine level was 2.30 ± 1.76 mg/dL, and the mean albumin/creatinine ratio was 4.85 ± 3.52. Among the podocyte proteins, urine synaptopodin showed strong correlation with serum creatinine by multivariate regression analysis (p < 0.001) and showed linear correlation (r = 0.429, p < 0.01). Urine podocyte proteins were increased in patients with diabetes, and synaptopodin showed the greatest significant difference (7.68 ± 5.61 vs. 2.56 ± 3.11, p < 0.001), but this might be associated with renal impairment. The urine albumin excretion did not differ between the diabetics and non-diabetics (p = 0.73). Conclusions: Urine synaptopodin is associated with serum creatinine elevation in the patients with glomerulonephritis including diabetic kidney disease regardless of urine albumin excretion. We suggest that the urine synaptopodin level can predict glomerular damage independently of the urine albumin excretion. PMID:27604800

  6. Glomerular tip adhesions predict the progression of IgA nephropathy

    PubMed Central

    2013-01-01

    Background Focal segmental glomerulosclerosis-like lesions have been proposed to be predictive factors for IgA nephropathy. This single center, retrospective cohort study was designed to clarify which clinical and pathological factors are predictive of decreased estimated glomerular filtration rate (eGFR) at 5 and 10 years in IgA nephropathy patients. Methods Of the 229 patients with IgA nephropathy who were admitted to Aichi Medical University Hospital between 1986 and 2010, 57 were included in this study during the 5 to 10 years after renal biopsy. Clinical, laboratory, and pathological parameters were analyzed by multiple linear regression analysis with backward elimination to determine independent risk factors. After identifying such factors, we compared patients with and without each factor using the Student’s t test, Wilcoxon test, or Mann–Whitney U test. Results Four variables were identified as predictive factors for progression of IgA nephropathy: initial eGFR (p = 0.0002), glomerular tip adhesion (p = 0.004), global sclerosis (p = 0.019), and diastolic blood pressure (p = 0.024). The annual decrease in eGFR of patients with (n = 9) or without glomerular tip adhesions (n = 48) was 4.13 ± 3.58 and 1.49 ± 2.89 ml/min/1.73 m2, respectively (p = 0.015). Serum total cholesterol levels were 231 ± 45 mg/dl and 196 ± 42 mg/dl, respectively (two-sided p = 0.064; one-sided p = 0.032). Conclusions The presence of glomerular tip adhesions predicts the progression of IgA nephropathy. High levels of serum total cholesterol may affect glomerular tip adhesions. PMID:24308295

  7. Renal glomerular fibrosis in a cat.

    PubMed

    Nakamura, S; Shibata, S; Shirota, K; Abe, K; Uetsuka, K; Nakayama, H; Goto, N; Doi, K

    1996-11-01

    Renal glomerular fibrosis was observed in a 1-year-old spayed female Japanese domestic cat that showed clinically advanced renal failure. In the glomeruli, increased homogeneous materials were stained strongly with aniline blue by Masson's trichrome and positive for anti-type III collagen antibody by immunohistochemical staining, causing mesangial sclerosis and capillary collapse. By electron microscopy, randomly arranged fibrils were observed in the expanded subendothelial and mesangial areas, and the fibrils showed periodicity characteristic of collagen fibers in longitudinal sections. These findings of glomerular lesions closely resemble those of human "collagenofibrotic glomerulonephropathy," which has recently been described as a new type of glomerulonephropathy. PMID:8952029

  8. Glomerular lesions induced in the rabbit by physicochemically altered homologous IgG.

    PubMed Central

    Cavalot, F.; Miyata, M.; Vladutiu, A.; Terranova, V.; Dubiski, S.; Burlingame, R.; Tan, E.; Brentjens, J.; Milgrom, F.; Andres, G.

    1992-01-01

    Immunization of rabbits with physicochemically altered homologous or even autologous IgG induces formation of antibodies combining with IgG of rabbit and of foreign species. Cardiac but not renal lesions were reported in such animals. This study examined the nephritogenic potential of the immune response to cationized or heat-aggregated homologous IgG of b9 or b4 allotype in rabbits of the b4 allotype. Rabbits injected with either b9 or b4 cationized IgG produced antibodies reactive with rabbit and human IgG and with histones; they also developed abnormal glomerular deposits of IgG b4 and C3 corresponding to alterations of the glomerular basement membranes (GBM). Rabbits injected with either b9 or b4 aggregated IgG developed antibodies reactive with rabbit and human IgG and abnormal glomerular deposits of IgG b4 and C3 in the GBM and in the mesangium with subendothelial and mesangial electron-dense deposits. Some rabbits in both groups had proliferative and exudative glomerulonephritis and proteinuria. The results showed that immunization of rabbits with physicochemically altered homologous IgG induces an immune response to rabbit and human IgG and to histones as well as glomerular deposits of autologous IgG and C3 and other glomerular lesions. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 11 Figure 12 Figure 13 Figure 14 Figure 15 Figure 16 Figure 17 Figure 18 Figure 19 Figure 20 Figure 21 Figure 22 Figure 23 Figure 24 Figure 25 Figure 26 Figure 27 Figure 28 Figure 29 Figure 30 PMID:1546743

  9. Water sample filtration unit

    USGS Publications Warehouse

    Skougstad, M.W.; Scarbro, G.F., Jr.

    1968-01-01

    A readily portable, all plastic, pressure filtration unit is described which greatly facilitates rapid micropore membrane field filtration of up to several liters of water with a minimum risk of inorganic chemical alteration or contamination of the sample. The unit accommodates standard 10.2-cm. (4-inch) diameter filters. The storage and carrying case serves as a convenient filter stand for both field and laboratory use.

  10. Water Filtration Products

    NASA Technical Reports Server (NTRS)

    1986-01-01

    American Water Corporation manufactures water filtration products which incorporate technology originally developed for manned space operations. The formula involves granular activated charcoal and other ingredients, and removes substances by catalytic reactions, mechanical filtration, and absorption. Details are proprietary. A NASA literature search contributed to development of the compound. The technology is being extended to a deodorizing compound called Biofresh which traps gas and moisture inside the unit. Further applications are anticipated.

  11. COMPARISONS OF VARIOUS FILTRATION MEDIA

    EPA Science Inventory

    The report reviews use of filtering materials in diatomaceous earth (DE) filtration, slow sand filtration, and coagulation-rapid rate filtration. For DE filtration, increased effluent clarity (lower turbidity) is generally attained at the expense of increased rates of head loss i...

  12. Epidemiology of Glomerular Disease in Southern Arizona

    PubMed Central

    Murugapandian, Sangeetha; Mansour, Iyad; Hudeeb, Mohammad; Hamed, Khaled; Hammode, Emad; Bijin, Babitha; Daheshpour, Sepehr; Thajudeen, Bijin; Kadambi, Pradeep

    2016-01-01

    Abstract Glomerulonephritis stands third in terms of the etiologies for end-stage kidney disease in the USA. The aim of this study was to look at the patterns of biopsy-proven glomerulonephritis based on data from a single center. Kidney biopsy specimens of all patients above the age of 18 years, over a 10-year period, who had diagnosis of nondiabetic glomerular disease, were selected for the study. The most common histopathological diagnosis was focal and segmental glomerulosclerosis (FSGS) (22.25%, 158/710) followed by membranous nephropathy (20.28%, 144/710) and immunoglobulin (Ig)A nephropathy (19.71%, 140/710). There was male preponderance in all histological variants except IgA nephropathy, lupus nephritis, and pauci-immune glomerulonephritis. The race distribution was uneven, and all histological variants, except minimal change disease and lupus nephritis, were more commonly seen in whites. In a separate analysis of the histological pattern in Hispanics, lupus nephritis was the most common pathology (28.70%, 62/216) followed by FSGS (18.05%, 39/216). In American Indian population, the most common pathology was IgA nephropathy (33.33%, 8/24) followed by FSGS (16.67%, 4/24). This study highlights the histopathological patterns of glomerular disease in southern Arizona. The data suggest regional and ethnic variations in glomerular disease that may point towards genetic or environmental influence in the pathogenesis of glomerular diseases. PMID:27149502

  13. Alterations in glomerular and tubular dynamics at 1 and 14 days simulated microgravity and after acute return to orthostasis

    NASA Technical Reports Server (NTRS)

    Tucker, Bryan J.; Mendonca, Margarida M.

    1995-01-01

    Head-down tilt (HDT) is utilized to simulate microgravity and produces a cephalad fluid shift, which results in alterations in fluid and electrolyte balance. These changes in volume homeostasis are due, in part, to alterations in multiple volume control mechanisms in which renal function is a major participant. We have previously demonstrated that glomerular filtration rate increases early in HDT and eventually returns to values not different from non-tilt measurements. This early increase in glomerular filtration rate was also demonstrated during days 2 and 8 of the SLS-1 mission. However, urine flow and electrolyte excretion does not parallel the alternations in glomerular filtration rate and the site of this change in nephron fluid reabsorption pattern has not been previously examined. Through determination of the location of alterations in tubular fluid reabsorption within the nephron, a more detailed hypothesis can be forwarded as to which specific neuro-humoral agents participating in control or renal function in microgravity conditions. the importance of this type of examination is that measurements in circulating neuro-humoral agents and urinary excretion patterns alone are not accurate predictors of how renal functional response may alter to head-down tilt or other models of simulated weightlessness. To examine this issue, renal micropuncture techniques were utilized in Munich-Wistar rats submitted 24 hour and 14 day head-down tilt, measuring all the determinants of glomerular ultrafiltration and obtaining data regarding segmental tubular fluid reabsorption. Following these measurements, the rats were returned to an orthostatic position and after 60 minutes, the measurements were repeated.

  14. Waste water filtration enhancement

    SciTech Connect

    Martin, H.L.

    1989-01-01

    Removal of submicron particles from process solutions and waste water is now economically achievable using a new Tyvek{reg sign} media in conventional filtration equipment. This new product greatly enhances filtration and allows use of the much improved filter aids and polymers which were recently developed. It has reduced operating costs and ensures a clean effluent discharge to the environment. This significant technical development is especially important to those who discharge to a small stream with low 7Q10 flow and must soon routinely pass the Toxicity tests that are being required by many States for NPDES permit renewal. The Savannah River Plant produces special nuclear materials for the US Government. Aluminum forming and metal finishing operations in M-Area, that manufacture fuel and target assemblies for the nuclear reactors, discharge to a waste water treatment facility using BAT hydroxide precipitation and filtration. The new Tyvek{reg sign} media and filter aids have achieved 55% less solids in the filtrate discharged to Tims Branch Creek, 15% less hazardous waste (dry filter cake), 150%-370% more filtration capacity, 74% lower materials purchase cost, 10% lower total M-Area manufacturing cost, and have improved safety. Performance with the improved polymers is now being evaluated.

  15. Long-term observations on tubular and glomerular function in cadmium-exposed persons.

    PubMed Central

    Piscator, M

    1984-01-01

    Four groups of cadmium-exposed persons, from different workplaces and with different types of exposure, have been followed for periods of 9-20 years. In one group the total observation time is over 30 years, since they were included in Friberg's original study. The studies include determination of inulin or creatinine clearance, protein excretion and specific indicators of renal tubular dysfunction. The results indicate that once tubular dysfunction is established, it is irreversible, even when it is minor. In some persons it was noted that the development of renal dysfunction seemed to be a multistage process. The initial stage is characterized by an increased excretion of low molecular weight proteins like beta 2-microglobulin and ribonuclease. After a period of several years with no or low exposure, there was a relatively sharp increase in excretion of total proteins and albumin and a decrease in glomerular filtration rate. This is interpreted as being the result of further increases in renal concentration of cadmium and in spread of cadmium along the tubules. Metallothionein absorption in the tubules, its catabolism and synthesis must play an important role for the development and progress of the tubular dysfunction. It was not possible to show that a decrease in glomerular filtration rate occurs before low molecular weight proteinuria. PMID:6376091

  16. Microfluidic colloid filtration

    PubMed Central

    Linkhorst, John; Beckmann, Torsten; Go, Dennis; Kuehne, Alexander J. C.; Wessling, Matthias

    2016-01-01

    Filtration of natural and colloidal matter is an essential process in today’s water treatment processes. The colloidal matter is retained with the help of micro- and nanoporous synthetic membranes. Colloids are retained in a “cake layer” – often coined fouling layer. Membrane fouling is the most substantial problem in membrane filtration: colloidal and natural matter build-up leads to an increasing resistance and thus decreasing water transport rate through the membrane. Theoretical models exist to describe macroscopically the hydrodynamic resistance of such transport and rejection phenomena; however, visualization of the various phenomena occurring during colloid retention is extremely demanding. Here we present a microfluidics based methodology to follow filter cake build up as well as transport phenomena occuring inside of the fouling layer. The microfluidic colloidal filtration methodology enables the study of complex colloidal jamming, crystallization and melting processes as well as translocation at the single particle level. PMID:26927706

  17. Microfluidic colloid filtration.

    PubMed

    Linkhorst, John; Beckmann, Torsten; Go, Dennis; Kuehne, Alexander J C; Wessling, Matthias

    2016-01-01

    Filtration of natural and colloidal matter is an essential process in today's water treatment processes. The colloidal matter is retained with the help of micro- and nanoporous synthetic membranes. Colloids are retained in a "cake layer" - often coined fouling layer. Membrane fouling is the most substantial problem in membrane filtration: colloidal and natural matter build-up leads to an increasing resistance and thus decreasing water transport rate through the membrane. Theoretical models exist to describe macroscopically the hydrodynamic resistance of such transport and rejection phenomena; however, visualization of the various phenomena occurring during colloid retention is extremely demanding. Here we present a microfluidics based methodology to follow filter cake build up as well as transport phenomena occuring inside of the fouling layer. The microfluidic colloidal filtration methodology enables the study of complex colloidal jamming, crystallization and melting processes as well as translocation at the single particle level. PMID:26927706

  18. Microfluidic colloid filtration

    NASA Astrophysics Data System (ADS)

    Linkhorst, John; Beckmann, Torsten; Go, Dennis; Kuehne, Alexander J. C.; Wessling, Matthias

    2016-03-01

    Filtration of natural and colloidal matter is an essential process in today’s water treatment processes. The colloidal matter is retained with the help of micro- and nanoporous synthetic membranes. Colloids are retained in a “cake layer” - often coined fouling layer. Membrane fouling is the most substantial problem in membrane filtration: colloidal and natural matter build-up leads to an increasing resistance and thus decreasing water transport rate through the membrane. Theoretical models exist to describe macroscopically the hydrodynamic resistance of such transport and rejection phenomena; however, visualization of the various phenomena occurring during colloid retention is extremely demanding. Here we present a microfluidics based methodology to follow filter cake build up as well as transport phenomena occuring inside of the fouling layer. The microfluidic colloidal filtration methodology enables the study of complex colloidal jamming, crystallization and melting processes as well as translocation at the single particle level.

  19. CENTRIFUGAL MEMBRANE FILTRATION

    SciTech Connect

    Daniel J. Stepan; Bradley G. Stevens; Melanie D. Hetland

    1999-10-01

    The overall project consists of several integrated research phases related to the applicability, continued development, demonstration, and commercialization of the SpinTek centrifugal membrane filtration process. Work performed during this reporting period consisted of Phase 2 evaluation of the SpinTek centrifugal membrane filtration technology and Phase 3, Technology Partnering. During Phase 1 testing conducted at the EERC using the SpinTek ST-IIL unit operating on a surrogate tank waste, a solids cake developed on the membrane surface. The solids cake was observed where linear membrane velocities were less than 17.5 ft/s and reduced the unobstructed membrane surface area up to 25%, reducing overall filtration performance. The primary goal of the Phase 2 research effort was to enhance filtration performance through the development and testing of alternative turbulence promoter designs. The turbulence promoters were designed to generate a shear force across the entire membrane surface sufficient to maintain a self-cleaning membrane capability and improve filtration efficiency and long-term performance. Specific Phase 2 research activities included the following: System modifications to accommodate an 11-in.-diameter, two-disk rotating membrane assembly; Development and fabrication of alternative turbulence promoter designs; Testing and evaluation of the existing and alternative turbulence promoters under selected operating conditions using a statistically designed test matrix; and Data reduction and analysis; The objective of Phase 3 research was to demonstrate the effectiveness of SpinTek's centrifugal membrane filtration as a pretreatment to remove suspended solids from a liquid waste upstream of 3M's WWL cartridge technology for the selective removal of technetium (Tc).

  20. MicroRNA-21 in glomerular injury.

    PubMed

    Lai, Jennifer Y; Luo, Jinghui; O'Connor, Christopher; Jing, Xiaohong; Nair, Viji; Ju, Wenjun; Randolph, Ann; Ben-Dov, Iddo Z; Matar, Regina N; Briskin, Daniel; Zavadil, Jiri; Nelson, Robert G; Tuschl, Thomas; Brosius, Frank C; Kretzler, Matthias; Bitzer, Markus

    2015-04-01

    TGF-β(1) is a pleotropic growth factor that mediates glomerulosclerosis and podocyte apoptosis, hallmarks of glomerular diseases. The expression of microRNA-21 (miR-21) is regulated by TGF-β(1), and miR-21 inhibits apoptosis in cancer cells. TGF-β(1)-transgenic mice exhibit accelerated podocyte loss and glomerulosclerosis. We determined that miR-21 expression increases rapidly in cultured murine podocytes after exposure to TGF-β(1) and is higher in kidneys of TGF-β(1)-transgenic mice than wild-type mice. miR-21-deficient TGF-β(1)-transgenic mice showed increased proteinuria and glomerular extracellular matrix deposition and fewer podocytes per glomerular tuft compared with miR-21 wild-type TGF-β(1)-transgenic littermates. Similarly, miR-21 expression was increased in streptozotocin-induced diabetic mice, and loss of miR-21 in these mice was associated with increased albuminuria, podocyte depletion, and mesangial expansion. In cultured podocytes, inhibition of miR-21 was accompanied by increases in the rate of cell death, TGF-β/Smad3-signaling activity, and expression of known proapoptotic miR-21 target genes p53, Pdcd4, Smad7, Tgfbr2, and Timp3. In American-Indian patients with diabetic nephropathy (n=48), albumin-to-creatinine ratio was positively associated with miR-21 expression in glomerular fractions (r=0.6; P<0.001) but not tubulointerstitial fractions (P=0.80). These findings suggest that miR-21 ameliorates TGF-β(1) and hyperglycemia-induced glomerular injury through repression of proapoptotic signals, thereby inhibiting podocyte loss. This finding is in contrast to observations in murine models of tubulointerstitial kidney injury but consistent with findings in cancer models. The aggravation of glomerular disease in miR-21-deficient mice and the positive association with albumin-to-creatinine ratio in patients with diabetic nephropathy support miR-21 as a feedback inhibitor of TGF-β signaling and functions. PMID:25145934

  1. MicroRNA-21 in Glomerular Injury

    PubMed Central

    Lai, Jennifer Y.; Luo, Jinghui; O’Connor, Christopher; Jing, Xiaohong; Nair, Viji; Ju, Wenjun; Randolph, Ann; Ben-Dov, Iddo Z.; Matar, Regina N.; Briskin, Daniel; Zavadil, Jiri; Nelson, Robert G.; Tuschl, Thomas; Brosius, Frank C.; Kretzler, Matthias

    2015-01-01

    TGF-β1 is a pleotropic growth factor that mediates glomerulosclerosis and podocyte apoptosis, hallmarks of glomerular diseases. The expression of microRNA-21 (miR-21) is regulated by TGF-β1, and miR-21 inhibits apoptosis in cancer cells. TGF-β1–transgenic mice exhibit accelerated podocyte loss and glomerulosclerosis. We determined that miR-21 expression increases rapidly in cultured murine podocytes after exposure to TGF-β1 and is higher in kidneys of TGF-β1–transgenic mice than wild-type mice. miR-21–deficient TGF-β1–transgenic mice showed increased proteinuria and glomerular extracellular matrix deposition and fewer podocytes per glomerular tuft compared with miR-21 wild-type TGF-β1–transgenic littermates. Similarly, miR-21 expression was increased in streptozotocin-induced diabetic mice, and loss of miR-21 in these mice was associated with increased albuminuria, podocyte depletion, and mesangial expansion. In cultured podocytes, inhibition of miR-21 was accompanied by increases in the rate of cell death, TGF-β/Smad3-signaling activity, and expression of known proapoptotic miR-21 target genes p53, Pdcd4, Smad7, Tgfbr2, and Timp3. In American-Indian patients with diabetic nephropathy (n=48), albumin-to-creatinine ratio was positively associated with miR-21 expression in glomerular fractions (r=0.6; P<0.001) but not tubulointerstitial fractions (P=0.80). These findings suggest that miR-21 ameliorates TGF-β1 and hyperglycemia-induced glomerular injury through repression of proapoptotic signals, thereby inhibiting podocyte loss. This finding is in contrast to observations in murine models of tubulointerstitial kidney injury but consistent with findings in cancer models. The aggravation of glomerular disease in miR-21–deficient mice and the positive association with albumin-to-creatinine ratio in patients with diabetic nephropathy support miR-21 as a feedback inhibitor of TGF-β signaling and functions. PMID:25145934

  2. Filtration by eyelashes

    NASA Astrophysics Data System (ADS)

    Vistarakula, Krishna; Bergin, Mike; Hu, David

    2010-11-01

    Nearly every mammalian and avian eye is rimmed with lashes. We investigate experimentally the ability of lashes to reduce airborne particle deposition in the eye. We hypothesize that there is an optimum eyelash length that maximizes both filtration ability and extent of peripheral vision. This hypothesis is tested using a dual approach. Using preserved heads from 36 species of animals at the American Museum of Natural History, we determine the relationship between eye size and eyelash geometry (length and spacing). We test the filtration efficacy of these geometries by deploying outdoor manikins and measuring particle deposition rate as a function of eyelash length.

  3. Magnetic-seeding filtration

    SciTech Connect

    Depaoli, D.

    1996-10-01

    This task will investigate the capabilities of magnetic-seeding filtration for the enhanced removal of magnetic and nonmagnetic particulates from liquids. This technology appies to a wide range of liquid wastes, including groundwater, process waters, and tank supernatant. Magnetic-seeding filtration can be used in several aspects of treatment, such as (1) removal of solids, particularly those in the colloidal-size range that are difficult to remove by conventional means; (2) removal of contaminants by precipitation processes; and (3) removal of contaminants by sorption processes.

  4. Organization of the pronephric filtration apparatus in zebrafish requires Nephrin, Podocin and the FERM domain protein Mosaic eyes

    PubMed Central

    Kramer-Zucker, Albrecht G.; Wiessner, Stephanie; Jensen, Abbie M.; Drummond, Iain A.

    2010-01-01

    Podocytes are specialized cells of the kidney that form the blood filtration barrier in the kidney glomerulus. The barrier function of podocytes depends upon the development of specialized cell–cell adhesion complexes called slit-diaphragms that form between podocyte foot processes surrounding glomerular blood vessels. Failure of the slit-diaphragm to form results in leakage of high molecular weight proteins into the blood filtrate and urine, a condition called proteinuria. In this work, we test whether the zebrafish pronephros can be used as an assay system for the development of glomerular function with the goal of identifying novel components of the slit-diaphragm. We first characterized the function of the zebrafish homolog of Nephrin, the disease gene associated with the congenital nephritic syndrome of the Finnish type, and Podocin, the gene mutated in autosomal recessive steroid-resistant nephrotic syndrome. Zebrafish nephrin and podocin were specifically expressed in pronephric podocytes and required for the development of pronephric podocyte cell structure. Ultrastructurally, disruption of nephrin or podocin expression resulted in a loss of slit-diaphragms at 72 and 96 h post-fertilization and failure to form normal podocyte foot processes. We also find that expression of the band 4.1/FERM domain gene mosaic eyes in podocytes is required for proper formation of slit-diaphragm cell–cell junctions. A functional assay of glomerular filtration barrier revealed that absence of normal nephrin, podocin or mosaic eyes expression results in loss of glomerular filtration discrimination and aberrant passage of high molecular weight substances into the glomerular filtrate. PMID:16102746

  5. Permselectivity of of the glomerular capillary wall. Studies of experimental glomerulonephritis in the rat using neutral dextran.

    PubMed Central

    Chang, R L; Deen, W M; Robertson, C R; Bennett, C M; Glassock, R J; Brenner, B M; Troy, J L; Ueki, I F; Rasmussen, B

    1976-01-01

    Polydisperse [3h] dextran was infused into eight Munich-Wistar rats in the early autologous phase of nephrotoxic serum nephritis (NSN), thereby permitting direct measurements of pressures and flows in surface glomeruli and fractional clearances for dextrans [(U/P) dextran/(U/P) inulin] ranging in radius from 18 to 42 A. Despite glomerular injury, evidenced morphologically and by a marked reduction in the glomerular capillary ultrafiltration coefficient, the glomerular filtration rate remained normal because of a compensating increase in the mean net ultrafiltration pressure. In NSN rats, as in normal controls, inulin was found to permeate the glomerular capillary wall without measurable restriction, and dextrans were shown to be neither secreted nor reabsorbed. For dextran radii of 18, 22, 26, 30, 34, 38, and 42 A, (U/P) dextran/(U/P) inulin in NSN and control rats, respectively, averaged 0.90 vs. 0.99, 0.81 vs. 0.97, 0.63 vs. 0.83, 0.38 vs 0.55, 0.20 vs. 0.30, 0.08 vs. 0.11, and 0.02 vs. 0.03. Using a theory based on macromolecular transport through pores, the results indicate that in NSN rats, effective pore radius is the same as in controls, approximately 50 A. In NSN, however, the ratio of total pore surface area to pore length, a measure of the number of pores, is reduced to approximately 1/3 that of control, probably due to a reduction in capillary surface area. These results suggest that proteinuria in glomerular disease is not due simply to increases in effective pore radius or number of pores, as previously believed. Using a second theoretical approach, based on the Kedem-Katchalsky flux equations, dextran permeability across glomerular capillaries was found to be slightly lower, and reflection coefficient slightly higher in NSN than in control rats. PMID:1262471

  6. Meiotic abnormalities

    SciTech Connect

    1993-12-31

    Chapter 19, describes meiotic abnormalities. These include nondisjunction of autosomes and sex chromosomes, genetic and environmental causes of nondisjunction, misdivision of the centromere, chromosomally abnormal human sperm, male infertility, parental age, and origin of diploid gametes. 57 refs., 2 figs., 1 tab.

  7. Water Treatment Technology - Filtration.

    ERIC Educational Resources Information Center

    Ross-Harrington, Melinda; Kincaid, G. David

    One of twelve water treatment technology units, this student manual on filtration provides instructional materials for six competencies. (The twelve units are designed for a continuing education training course for public water supply operators.) The competencies focus on the following areas: purposes of sedimentation basins and flocculation…

  8. NF-κB signaling maintains the survival of cadmium-exposed human renal glomerular endothelial cells

    PubMed Central

    Zhang, Hongyan; Li, Liqun; Wang, Yifan; Dong, Fengyun; Chen, Xiaocui; Liu, Fuhong; Xu, Dongmei; Yi, Fan; Kapron, Carolyn M.; Liu, Ju

    2016-01-01

    The kidney is one of the primary organs targeted by cadmium (Cd), a widely distributed environmental pollutant. The glomerular endothelium is the major component of the glomerular filtration barrier. However, the effects of Cd on glomerular endothelial cells remain largely unknown. For this purpose, we aimed to determine the effects of low dose Cd on the survival of human renal glomerular endothelial cells (HRGECs). Cultured HRGECs were exposed to 4 µM cadmium chloride (CdCl2) and examined at different time-points. We found that Cd activates the nuclear factor-κB (NF-κB) pathway without inducing the apoptosis of HRGECs. Pre-treating the cells with pyrrolidine dithiocarbamate (PDTC), a potent NF-κB inhibitor, prior to Cd exposure triggered extensive cell death (73.5%). In addition, Cd activates the c-Jun N-terminal kinase (JNK) pathway, and inhibition of the NF-κB pathway significantly elevates Cd-induced JNK phosphorylation in HRGECs (p<0.01). The combination treatment of PDTC and SP600125, a JNK pathway inhibitor, increased the survival of Cd-stimulated HRGECs compared with those cells treated with PDTC alone (p<0.05). Taken together, these findings demonstrate that the NF-κB pathway plays an essential role in maintaining the survival of Cd-exposed HRGECs. PMID:27315281

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

    PubMed

    Kang, Min-Kyung; Lim, Soon Sung; Lee, Jae-Yong; Yeo, Kyung Mok; Kang, Young-Hee

    2013-01-01

    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. PMID:24278186

  10. Congenital Abnormalities

    MedlinePlus

    ... serious health problems (e.g. Down syndrome ). Single-Gene Abnormalities Sometimes the chromosomes are normal in number, ... blood flow to the fetus impair fetal growth. Alcohol consumption and certain drugs during pregnancy significantly increase ...

  11. Craniofacial Abnormalities

    MedlinePlus

    ... of the skull and face. Craniofacial abnormalities are birth defects of the face or head. Some, like cleft ... palate, are among the most common of all birth defects. Others are very rare. Most of them affect ...

  12. Walking abnormalities

    MedlinePlus

    ... include: Arthritis of the leg or foot joints Conversion disorder (a psychological disorder) Foot problems (such as a ... injuries. For an abnormal gait that occurs with conversion disorder, counseling and support from family members are strongly ...

  13. Chromosome Abnormalities

    MedlinePlus

    ... decade, newer techniques have been developed that allow scientists and doctors to screen for chromosomal abnormalities without using a microscope. These newer methods compare the patient's DNA to a normal DNA ...

  14. Nail abnormalities

    MedlinePlus

    Nail abnormalities are problems with the color, shape, texture, or thickness of the fingernails or toenails. ... Fungus or yeast cause changes in the color, texture, and shape of the nails. Bacterial infection may ...

  15. Urinary CYP Eicosanoid Excretion Correlates with Glomerular Filtration in African-Americans with Chronic Kidney Disease

    PubMed Central

    Dreisbach, Albert W; Smith, Stanley V; Kyle, Patrick B; Ramaiah, Manjunath; Amenuke, Margaret; Garrett, Michael R; Lirette, Seth T; Griswold, Michael E; Roman, Richard J

    2015-01-01

    Previous studies have indicated that cytochrome P450 (CYP) metabolites of arachidonic acid (AA), i.e., 20-hydroxyeicosatetraenoic acid (20-HETE) and epoxyeicosatrienoic acids (EETs), play an important role in the regulation of renal tubular and vascular function. The present study for the first time profiled HETEs and epoxygenase derived dihydroxyeicosatetraenoic acid diHETEs levels in spot urines and plasma in 262 African American patients from the University of Mississippi Chronic Kidney Disease Clinic and 31 African American controls. Significant correlations in eGFR and urinary 20-HETE/creatinine and 19-HETE/ creatinine levels were observed. The eGFR increased by 17.47 [p=0.001] and 60.68 [(p=0.005] ml/min/ for each ng/mg increase in 20-HETE and 19-HETE levels, respectively. Similar significant positive associations were found between the other urinary eicosanoids and eGFR and also with 19-HETE/urine creatinine concentration and proteinuria. We found that approximately 80% of plasma HETEs and 30% diHETEs were glucuronidated and the fractional excretion of 20-HETE was less than 1%. These results suggest that there is a significant hepatic source of urinary 20-HETE glucuronide and EETs with extensive renal biotransformation to metabolites which may play a role in the pathogenesis of CKD. PMID:25151892

  16. The impact of hormonal contraceptives on blood pressure, urinary albumin excretion and glomerular filtration rate

    PubMed Central

    Atthobari, Jarir; Gansevoort, Ron T; Visser, Sipke T; de Jong, Paul E; de Jong-van den Berg, Lolkje T W

    2007-01-01

    Aim In short-term studies, hormonal contraceptives (HC) have been suggested to induce a rise in blood pressure (BP) and urinary albumin excretion (UAE), while the effect of HC in renal function (GFR) is still under debate. Data on long-term and withdrawal effects of HC use on these outcomes are, however, not available. We therefore studied whether the start and cessation of HC induce changes in BP, UAE and GFR. Methods We used data from the PREVEND Study, a prospective cohort of subjects aged 28–75 years. Eligible were women aged ≤ 45 years with complete clinical and pharmacy data on baseline and follow-up screening (4 years later). Multivariate regression analysis was used to estimate the effects of HC on BP, UAE and GFR in those who started (n = 73), stopped (n = 117) or continued (n = 183) with those who never used HC (n = 286) as the reference group. Results BP increased among starters and fell in stoppers. These changes compared with never-users were statistically significant, even after adjustment for relevant variables. UAE increased by 14.2% in starters (P = 0.074) and fell by 10.6% in stoppers (P = 0.021), while GFR fell by 6.3% in starters (P < 0.001) and did not change in stoppers. The effects of stopping HC on UAE and GFR were significantly different compared with changes among never-users, even after adjustment for other variables (P = 0.023 and 0.036, respectively). Conclusions The start of HC was independently associated with worsening of BP, UAE and GFR, while stopping HC use resulted in an improvement. These data suggest that long-term HC use (aged 28–45 years) may be deleterious from the cardiovascular and renal point of view, but stopping may result in correction of these effects. PMID:17274790

  17. Quantification of single-kidney glomerular filtration rate with electron-beam computed tomography

    NASA Astrophysics Data System (ADS)

    Lerman, Lilach O.; Ritman, Erik L.; Pelaez, Laura I.; Sheedy, Patrick F., II; Krier, James D.

    2000-04-01

    The ability to accurately and noninvasively quantify single- kidney GFR could be invaluable for assessment of renal function. We developed a model that enables this measurement with EBCT. To examine the reliability of this method, EBCT renal flow and volume studies after contrast media administration were performed in pigs with unilateral renal artery stenosis (Group 1), controls (Group 2), and simultaneously with inulin clearance (Group 3). Renal flow curves, obtained from the bilateral renal cortex and medulla, depicted transit of the contrast through the vascular and tubular compartments, and were fitted using extended gamma- variate functions. Renal blood flow was calculated as the sum of products of cortical and medullary perfusions and volumes. Normalized GFR (mL/min/cc) was calculated using the rate (maximal slope) of proximal tubular contrast accumulation, and EBCT-GFR as normalized GFR* cortical volume. In Group 1, the decreased GFR of the stenotic kidney correlated well with its decreased volume and RBF, and with the degree of stenosis (r equals -0.99). In Group 3, EBCT-GFR correlated well with inulin clearance (slope 1.1, r equals 0.81). This novel approach can be very useful for quantification of concurrent regional hemodynamics and function in the intact kidneys, in a manner potentially applicable to humans.

  18. Sex Differences in Associations Among Obesity, Metabolic Abnormalities, and Chronic Kidney Disease in Japanese Men and Women

    PubMed Central

    Sakurai, Masaru; Kobayashi, Junji; Takeda, Yasuo; Nagasawa, Shin-Ya; Yamakawa, Junichi; Moriya, Junji; Mabuchi, Hiroshi; Nakagawa, Hideaki

    2016-01-01

    Aims The present study aimed to investigate relationships among abdominal obesity, metabolic abnormalities, and the prevalence of chronic kidney disease (CKD) in relatively lean Japanese men and women. Participants and methods The participants included 8133 men and 15 934 women between 40 and 75 years of age recruited from the government health check-up center in Kanazawa City, Japan. The prevalence of abdominal obesity, high blood pressure, dyslipidemia, and high fasting plasma glucose levels were assessed according to the Japanese criteria for metabolic syndrome. The estimated glomerular filtration rate (eGFR) was calculated using the modified Modification of Diet in Renal Disease equation for the Japanese population, and participants with an eGFR <60 mL/min/1.73 m2 and/or proteinuria were diagnosed with CKD. Results Overall, 23% of males and 14% of females met criteria for CKD. Having more numerous complicated metabolic abnormalities was significantly associated with a higher odds ratio (OR) of CKD for men and women, irrespective of abdominal obesity. However, there was a sex difference in the OR of CKD for obese participants without metabolic abnormalities, such that abdominal obesity without metabolic abnormalities was significantly associated with a higher OR for men (multivariate-adjusted OR 1.63; 95% confidence interval [CI], 1.16–2.28) but not for women (OR 1.01; 95% CI, 0.71–1.44). Conclusions The present findings demonstrated that obesity without metabolic abnormalities was associated with a higher risk of CKD in men but not women in a relatively lean Japanese population. PMID:27087606

  19. New Insights into Glomerular Parietal Epithelial Cell Activation and Its Signaling Pathways in Glomerular Diseases

    PubMed Central

    Su, Hua; Chen, Shan; He, Fang-Fang; Wang, Yu-Mei; Bondzie, Philip; Zhang, Chun

    2015-01-01

    The glomerular parietal epithelial cells (PECs) have aroused an increasing attention recently. The proliferation of PECs is the main feature of crescentic glomerulonephritis; besides that, in the past decade, PEC activation has been identified in several types of noninflammatory glomerulonephropathies, such as focal segmental glomerulosclerosis, diabetic glomerulopathy, and membranous nephropathy. The pathogenesis of PEC activation is poorly understood; however, a few studies delicately elucidate the potential mechanisms and signaling pathways implicated in these processes. In this review we will focus on the latest observations and concepts about PEC activation in glomerular diseases and the newest identified signaling pathways in PEC activation. PMID:25866774

  20. Rapid, dynamic changes in glomerular permeability to macromolecules during systemic angiotensin II (ANG II) infusion in rats.

    PubMed

    Axelsson, Josefin; Rippe, Anna; Oberg, Carl M; Rippe, Bengt

    2012-09-15

    The actions of systemic angiotensin II (ANG II) infusions on glomerular permeability were investigated in vivo. In anesthetized Wistar rats (250-280 g), the left ureter was cannulated for urine collection, while simultaneously blood access was achieved. Rats were continuously infused intravenously with either of four doses of ANG II ranging from 16 ng·kg(-1)·min(-1) (Lo-ANG II) to 1.82 μg·kg(-1)·min(-1) (Hi-ANG II), and in separate experiments with aldosterone (Aldo; 0.22 mg·kg(-1)·min(-1)), or with the calcium channel blocker nimodipine, or with the Aldo antagonist spironolactone together with a high ANG II dose (910 ng·kg(-1)·min(-1); Hi-Int-ANG II), respectively, and with polydisperse FITC-Ficoll-70/400 (molecular radius 10-80 Å) and (51)Cr-EDTA. Plasma and urine samples were taken at 5, 15, 30, 60, and 120 min and analyzed by high performance size-exclusion chromatography for determination of glomerular sieving coefficients (θ) to Ficoll. Mean arterial pressure (MAP) and glomerular filtration rate (GFR) were also assessed. For ANG II, there was a rapid, marked, partly reversible increase in glomerular permeability (θ) for Ficoll molecules >34 Å in radius, peaking at 5-15 min, which was completely abrogated by the ANG II blocker candesartan but not affected by spironolactone at 15 and 30 min. For Aldo, the response was similar to that found for the lowest dose of ANG II infused. For the two highest ANG II doses given (Hi-Int-ANG II and Hi-ANG II), GFR decreased transiently, concomitant with marked, sustained increases in MAP. Nimodipine completely blocked all hemodynamic ANG II actions, whereas the glomerular permeability response remained unchanged. Thus ANG II directly increased glomerular permeability independently of its hemodynamic actions and largely independently of the concomitant Aldo response. The ANG II-induced increases in glomerular permeability were, according to a two-pore and a log-normal distributed pore model, compatible with an

  1. Liquid filtration simulation

    SciTech Connect

    Corey, I.; Bergman, W.

    1996-06-01

    We have a developed a computer code that simulates 3-D filtration of suspended particles in fluids in realistic filter structures. This code, being the most advanced filtration simulation package developed to date, provides LLNL and DOE with new capabilities to address problems in cleaning liquid wastes, medical fluid cleaning, and recycling liquids. The code is an integrated system of commercially available and LLNL-developed software; the most critical are the computational fluid dynamics (CFD) solver and the particle transport program. For the CFD solver, we used a commercial package based on Navier-Stokes equations and a LLNL-developed package based on Boltzman-lattice gas equations. For the particle transport program, we developed a cod based on the 3-D Langevin equation of motion and the DLVO theory of electrical interactions. A number of additional supporting packages were purchased or developed to integrate the simulation tasks and to provide visualization output.

  2. Transcriptional Landscape of Glomerular Parietal Epithelial Cells

    PubMed Central

    Gharib, Sina A.; Pippin, Jeffrey W.; Ohse, Takamoto; Pickering, Scott G.; Krofft, Ronald D.; Shankland, Stuart J.

    2014-01-01

    Very little is known about the function of glomerular parietal epithelial cells (PECs). In this study, we performed genome-wide expression analysis on PEC-enriched capsulated vs. PEC-deprived decapsulated rat glomeruli to determine the transcriptional state of PECs under normal conditions. We identified hundreds of differentially expressed genes that mapped to distinct biologic modules including development, tight junction, ion transport, and metabolic processes. Since developmental programs were highly enriched in PECs, we characterized several of their candidate members at the protein level. Collectively, our findings confirm that PECs are multifaceted cells and help define their diverse functional repertoire. PMID:25127402

  3. Urinary Thrombin: A Novel Marker of Glomerular Inflammation for the Diagnosis of Crescentic Glomerulonephritis (Prospective Observational Study)

    PubMed Central

    Kitamoto, Yasunori; Arizono, Kenji; Fukui, Hiroyoshi; Tomita, Kimio; Kitamura, Hiroshi; Taguma, Yoshio; Imamura, Takahisa

    2015-01-01

    Background Crescentic glomerulonephritis (CresGN), an uncommon rapidly progressive disease, is characterized by severe glomerular inflammation with fibrin deposition. The lack of specific CresGN biomarkers delays diagnosis and threatens life. Because fibrin deposits in CresGN glomeruli indicate thrombin generation, we hypothesized that thrombin is excreted in urine and is a specific CresGN biomarker. Methods We measured urinary thrombin activity in 200 untreated patients (17 with CresGN, 183 with primary glomerulonephritis) and controls (8 patients with healed CresGN, 11 with nephrosclerosis, and 10 with tubulointerstitial nephritis, and 66 healthy volunteers). CresGN types included 15 pauci-immune and 2 immune complex. We assessed the diagnostic accuracy of thrombinuria in 169 patients with hematuria and proteinuria. Renal biopsy tissues were immunostained for tissue factor and fibrin. We analyzed the relationship of thrombinuria to plasma thrombin-antithrombin complex, hematuria, proteinuria, glomerular filtration rate, glomerular fibrin deposition, antineutrophil cytoplasmic antibodies (ANCAs), and C-reactive protein (CRP). We studied changes in thrombin activities after glucocorticoid treatment in 12 patients with thrombinuria. Results The highest thrombinuria occurrence was in CresGN (70.6%), followed by membranoproliferative glomerulonephritis (41.7%), IgA nephropathy (9.2%), and acute glomerulonephritis (0%). More than 75% of patients with nonproliferative glomerulonephritis manifested no thrombinuria. No controls had thrombinuria. Thrombinuria showed high CresGN specificity (90.1%) and moderate sensitivity (70.6%) and was detected in 4 of 7 patients with ANCA-negative CresGN. In CresGN, thrombinuria was associated with fibrin deposition in glomerular extracapillary tissue, where monocytes/macrophages expressed tissue factor. Thrombinuria in CresGN was unrelated to plasma thrombin-antithrombin complex, hematuria, proteinuria, glomerular filtration rate, and

  4. Evidence for glomerular actions of epidermal growth factor in the rat.

    PubMed Central

    Harris, R C; Hoover, R L; Jacobson, H R; Badr, K F

    1988-01-01

    postglomerular arterioles, results in acute major reductions in the rates of glomerular filtration and perfusion. Images PMID:3262122

  5. Extracellular purines' action on glomerular albumin permeability in isolated rat glomeruli: insights into the pathogenesis of albuminuria.

    PubMed

    Kasztan, Małgorzata; Piwkowska, Agnieszka; Kreft, Ewelina; Rogacka, Dorota; Audzeyenka, Irena; Szczepanska-Konkel, Mirosława; Jankowski, Maciej

    2016-07-01

    Purinoceptors (adrengeric receptors and P2 receptors) are expressed on the cellular components of the glomerular filtration barrier, and their activation may affect glomerular permeability to albumin, which may ultimately lead to albuminuria, a well-established risk factor for the progression of chronic kidney disease and development of cardiovascular diseases. We investigated the mechanisms underlying the in vitro and in vivo purinergic actions on glomerular filter permeability to albumin by measuring convectional albumin permeability (Palb) in a single isolated rat glomerulus based on the video microscopy method. Primary cultured rat podocytes were used for the analysis of Palb, cGMP accumulation, PKG-Iα dimerization, and immunofluorescence. In vitro, natural nucleotides (ATP, ADP, UTP, and UDP) and nonmetabolized ATP analogs (2-meSATP and ATP-γ-S) increased Palb in a time- and concentration-dependent manner. The effects were dependent on P2 receptor activation, nitric oxide synthase, and cytoplasmic guanylate cyclase. ATP analogs significantly increased Palb, cGMP accumulation, and subcortical actin reorganization in a PKG-dependent but nondimer-mediated route in cultured podocytes. In vivo, 2-meSATP and ATP-γ-S increased Palb but did not significantly affect urinary albumin excretion. Both agonists enhanced the clathrin-mediated endocytosis of albumin in podocytes. A product of adenine nucleotides hydrolysis, adenosine, increased the permeability of the glomerular barrier via adrenergic receptors in a dependent and independent manner. Our results suggest that the extracellular nucleotides that stimulate an increase of glomerular Palb involve nitric oxide synthase and cytoplasmic guanylate cyclase with actin reorganization in podocytes. PMID:27076649

  6. Cross talk between miR-214 and PTEN attenuates glomerular hypertrophy under diabetic conditions.

    PubMed

    Wang, Xiaoxia; Shen, E; Wang, Yanzhe; Li, Junhui; Cheng, Dongsheng; Chen, Yuqiang; Gui, Dingkun; Wang, Niansong

    2016-01-01

    Glomerular mesangial cells (MCs) hypertrophy is one of the earliest pathological abnormalities in diabetic nephropathy (DN), which correlates with eventual glomerulosclerosis. This study aimed to investigate the therapeutic role of miRNA in diabetic glomerular MCs hypertrophy and synthesis of extracellular matrix (ECM). Microarray analysis revealed a significant up-regulation of miR-214 in the renal cortex of diabetic db/db mice, which was confirmed by real-time PCR of isolated glomeruli and primary cultured human MCs. In vitro studies showed that inhibition of miR-214 significantly reduced expression of α-SMA, SM22 and collagen IV, and partially restored phosphatase and tensin homolog (PTEN) protein level in high glucose-stimulated human MCs. Furthermore, we identified PTEN as the target of miR-214 by a luciferase assay in HEK293 cells. Moreover, overexpression of PTEN ameliorated miR-214-mediated diabetic MC hypertrophy while knockdown of PTEN mimicked the MC hypertrophy. In vivo study further confirmed that inhibition of miR-214 significantly decreased the expression of SM22, α-SMA and collagen IV, partially restored PTEN level, and attenuated albuminuria and mesangial expansion in db/db mice. In conclusion, cross talk between miR-214 and PTEN attenuated glomerular hypertrophy under diabetic conditions in vivo and in vitro. Therefore, miR-214 may represent a novel therapeutic target for DN. PMID:27549568

  7. Cross talk between miR-214 and PTEN attenuates glomerular hypertrophy under diabetic conditions

    PubMed Central

    Wang, Xiaoxia; Shen, E.; Wang, Yanzhe; Li, Junhui; Cheng, Dongsheng; Chen, Yuqiang; Gui, Dingkun; Wang, Niansong

    2016-01-01

    Glomerular mesangial cells (MCs) hypertrophy is one of the earliest pathological abnormalities in diabetic nephropathy (DN), which correlates with eventual glomerulosclerosis. This study aimed to investigate the therapeutic role of miRNA in diabetic glomerular MCs hypertrophy and synthesis of extracellular matrix (ECM). Microarray analysis revealed a significant up-regulation of miR-214 in the renal cortex of diabetic db/db mice, which was confirmed by real-time PCR of isolated glomeruli and primary cultured human MCs. In vitro studies showed that inhibition of miR-214 significantly reduced expression of α-SMA, SM22 and collagen IV, and partially restored phosphatase and tensin homolog (PTEN) protein level in high glucose-stimulated human MCs. Furthermore, we identified PTEN as the target of miR-214 by a luciferase assay in HEK293 cells. Moreover, overexpression of PTEN ameliorated miR-214-mediated diabetic MC hypertrophy while knockdown of PTEN mimicked the MC hypertrophy. In vivo study further confirmed that inhibition of miR-214 significantly decreased the expression of SM22, α-SMA and collagen IV, partially restored PTEN level, and attenuated albuminuria and mesangial expansion in db/db mice. In conclusion, cross talk between miR-214 and PTEN attenuated glomerular hypertrophy under diabetic conditions in vivo and in vitro. Therefore, miR-214 may represent a novel therapeutic target for DN. PMID:27549568

  8. Glomerular adaptations to renal injury or ablation. Role of capillary hypertension in the pathogenesis of progressive glomerulosclerosis.

    PubMed

    Rennke, H G

    1988-01-01

    A reduction in the effective glomerular capillary surface available for filtration by renal ablation or acquired renal disease results in functional and structural adaptations which lead to endothelial, mesangial and epithelial cell dysfunction. The structural lesions that ensue include capillary microthrombosis, mesangial expansion, microaneurysm formation, epithelial cell detachment with hyalin deposition, and basement membrane thickening. These alterations lead to segmental and eventually global glomerulosclerosis, closing the loop of a positive feedback mechanism that perpetuates and accelerates the microvascular damage. Dietary, hormonal, and as yet poorly identified constitutional factors can modulate the hemodynamic response to the original insult and offer an opportunity to influence this process therapeutically. PMID:3061399

  9. Endothelium-derived vasoactive mediators and renal glomerular function.

    PubMed

    Ballermann, B J; Marsden, P A

    1991-12-01

    Glomerular endothelial cells are located in extremely close proximity to glomerular mesangial cells, without intervening basement membrane. This close apposition of the two cell types suggest that interactions between the cells should readily occur. Given that endothelial cells are known to produce mediators which regulate the tone of underlying vascular smooth muscle cells, the hypothesis that glomerular endothelial cells can produce endothelium-derived relaxation factor and the potent vasoconstrictor endothelin-1 was examined. Pure cultures of glomerular endothelial cells were established in vitro. The cells expressed a number of characteristics that identified them as endothelial cells, namely Factor VIII related antigen, angiotensin I converting enzyme, and uptake of acetylated LDL. The glomerular endothelial cells responded to the calcium-mobilizing agonists bradykinin, ATP, thrombin and platelet activating factor with a significant rise in cytosolic calcium concentrations. Under basal conditions, the glomerular endothelial cells produced a mediator pharmacologically indistinguishable from EDRF, which raised cGMP levels in co-incubated mesangial cells approximately 4 to 5-fold. The calcium-mobilizing agonists further stimulated EDRF release by glomerular endothelial cells. Glomerular endothelial cells in culture were also found to express mRNA for endothelin-1, and to secrete this peptide into their supernatant. Furthermore, the calcium-mobilizing agonists markedly stimulated endothelin-1 release by activating endothelin-1 gene transcription. Glomerular mesangial cells respond to EDRF with a rise in cytosolic cGMP concentration and relaxation, and to endothelin-1 with a rise in cytosolic calcium concentration and contraction. It is therefore proposed that local release of EDRF and endothelin-1 by glomerular endothelial cells may participate in the regulation of glomerular hemodynamics through alterations in mesangial cell contractile tone. PMID:1794204

  10. Dynamic optical filtration

    NASA Technical Reports Server (NTRS)

    Chretien, Jean-Loup (Inventor); Lu, Edward T. (Inventor)

    2005-01-01

    A dynamic optical filtration system and method effectively blocks bright light sources without impairing view of the remainder of the scene. A sensor measures light intensity and position so that selected cells of a shading matrix may interrupt the view of the bright light source by a receptor. A beamsplitter may be used so that the sensor may be located away from the receptor. The shading matrix may also be replaced by a digital micromirror device, which selectively sends image data to the receptor.

  11. Dynamic Optical Filtration

    NASA Technical Reports Server (NTRS)

    Chretien, Jean-Loup (Inventor); Lu, Edward T. (Inventor)

    2005-01-01

    A dynamic optical filtration system and method effectively blocks bright light sources without impairing view of the remainder of the scene. A sensor measures light intensity and position so that selected cells of a shading matrix may interrupt the view of the bright light source by a receptor. A beamsplitter may be used so that the sensor may be located away from the receptor. The shading matrix may also be replaced by a digital micromirror device, which selectively sends image data to the receptor.

  12. Magnetic-seeding filtration

    SciTech Connect

    DePaoli, D.W.; Tsouris, C.; Yiacoumi, Sotira

    1997-10-01

    Magnetic-seeding filtration is a technology under development for the enhanced removal of magnetic and non-magnetic particulates from liquids. This process involves the addition of a small amount of magnetic seed particles (such as naturally occurring iron oxide) to a waste suspension, followed by treatment with a magnetic filter. Non-magnetic and weakly magnetic particles are made to undergo nonhomogeneous flocculation with the seed particles, forming flocs of high magnetic susceptibility that are readily removed by a conventional high-gradient magnetic filter. This technology is applicable to a wide range of liquid wastes, including groundwater, process waters, and tank supernatants. Magnetic-seeding filtration may be used in several aspects of treatment, such as (1) removal of solids, particularly those in the colloidal size range that are difficult to remove by conventional means; (2) removal of contaminants by precipitation processes; and (3) removal of contaminants by sorption processes. Waste stream characteristics for which the technology may be applicable include (1) particle sizes ranging from relatively coarse (several microns) to colloidal particles, (2) high or low radiation levels, (3) broad-ranging flow rates, (4) low to moderate solids concentration, (5) cases requiring high decontamination factors, and (6) aqueous or non-aqueous liquids. At this point, the technology is at the bench-scale stage of development; laboratory studies and fundamental modeling are currently being employed to determine the capabilities of the process.

  13. Drug-induced glomerular disease: direct cellular injury.

    PubMed

    Markowitz, Glen S; Bomback, Andrew S; Perazella, Mark A

    2015-07-01

    The potential of medications to cause kidney injury is well known. Although nephrotoxicity is most commonly associated with injury in the tubulointerstitial compartment as either acute tubular necrosis or acute interstitial nephritis, a growing body of literature has also highlighted the potential for drug-induced glomerular lesions. This review surveys the three primary patterns of drug-induced glomerular diseases stratified by the cell type at which the glomerular lesion is focused: visceral epithelial cell (or podoctye) injury, endothelial cell injury, and mesangial cell injury. A number of commonly prescribed medications, including IFNs, bisphosphonates, nonsteroidal anti-inflammatory drugs, antiplatelet agents, and antiangiogenesis drugs, that are both prescribed and available over the counter, have been implicated in these iatrogenic forms of glomerular disease. Recognition of these drug-induced etiologies of glomerular disease and rapid discontinuation of the offending agent are critical to maximizing the likelihood of renal function recovery. PMID:25862776

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

    PubMed Central

    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

  15. A reassessment of soluble urokinase-type plasminogen activator receptor in glomerular disease

    PubMed Central

    Spinale, Joann M.; Mariani, Laura H.; Kapoor, Shiv; Zhang, Jidong; Weyant, Robert; Song, Peter X.; Wong, Hetty N.; Troost, Jonathan P.; Gadegbeku, Crystal A.; Gipson, Debbie S.; Kretzler, Matthias; Nihalani, Deepak; Holzman, Lawrence B.

    2014-01-01

    It has been suggested that soluble urokinase receptor (suPAR) is a causative circulating factor for and a biomarker of focal and segmental glomerulosclerosis (FSGS). Here we undertook validation of these assumptions in both mouse and human models. Injection of recombinant suPAR in wild-type mice did not induce proteinuria within 24 hours. Moreover, a disease phenotype was not seen in an inducible transgenic mouse model that maintained elevated suPAR concentrations for 6 weeks. Plasma and urine suPAR concentrations were evaluated as clinical biomarkers in 241 patients with glomerular disease from the prospective, longitudinal multi-center observational NEPTUNE cohort. The serum suPAR concentration at baseline inversely correlated with estimated glomerular filtration rate (eGFR) and the urine suPAR/creatinine ratio positively correlated with the urine protein/creatinine ratio. After adjusting for eGFR and urine protein, neither the serum nor urine suPAR level was an independent predictor of FSGS histopathology. A multivariable mixed-effects model of longitudinal data evaluated the association between the change in serum suPAR concentration from baseline with eGFR. After adjusting for baseline suPAR concentration, age, gender, proteinuria and time, the change in suPAR from baseline was associated with eGFR, but this association was not different for patients with FSGS as compared to other diagnoses. Thus, these results do not support a pathological role for suPAR in FSGS. PMID:25354239

  16. A reassessment of soluble urokinase-type plasminogen activator receptor in glomerular disease.

    PubMed

    Spinale, Joann M; Mariani, Laura H; Kapoor, Shiv; Zhang, Jidong; Weyant, Robert; Song, Peter X; Wong, Hetty N; Troost, Jonathan P; Gadegbeku, Crystal A; Gipson, Debbie S; Kretzler, Matthias; Nihalani, Deepak; Holzman, Lawrence B

    2015-03-01

    It has been suggested that soluble urokinase receptor (suPAR) is a causative circulating factor for and a biomarker of focal and segmental glomerulosclerosis (FSGS). Here we undertook validation of these assumptions in both mouse and human models. Injection of recombinant suPAR in wild-type mice did not induce proteinuria within 24 h. Moreover, a disease phenotype was not seen in an inducible transgenic mouse model that maintained elevated suPAR concentrations for 6 weeks. Plasma and urine suPAR concentrations were evaluated as clinical biomarkers in 241 patients with glomerular disease from the prospective, longitudinal multicenter observational NEPTUNE cohort. The serum suPAR concentration at baseline inversely correlated with estimated glomerular filtration rate (eGFR) and the urine suPAR/creatinine ratio positively correlated with the urine protein/creatinine ratio. After adjusting for eGFR and urine protein, neither the serum nor urine suPAR level was an independent predictor of FSGS histopathology. A multivariable mixed-effects model of longitudinal data evaluated the association between the change in serum suPAR concentration from baseline with eGFR. After adjusting for baseline suPAR concentration, age, gender, proteinuria, and time, the change in suPAR from baseline was associated with eGFR, but this association was not different for patients with FSGS as compared with other diagnoses. Thus these results do not support a pathological role for suPAR in FSGS. PMID:25354239

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

    PubMed

    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 [Nle(4), D-Phe(7)]-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. Renal scintigraphy in insulin-dependent diabetes mellitus: Early glomerular and urologic dysfunction

    SciTech Connect

    Poirier, J.Y.; Moisan, A.; Le Cloirec, J.; Siemen, C.; Yaouanq, J.; Edan, G.; Herry, J.Y. )

    1990-07-01

    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.

  19. CENTRIFUGAL MEMBRANE FILTRATION

    SciTech Connect

    William A. Greene; Patricia A. Kirk; Richard Hayes; Joshua Riley

    2005-10-28

    SpinTek Membrane Systems, Inc., the developer of a centrifugal membrane filtration technology, has engineered and developed a system for use within the U.S. Department of Energy (DOE) Environmental Management (EM) Program. The technology uses supported microporous membranes rotating at high rpm, under pressure, to separate suspended and colloidal solids from liquid streams, yielding a solids-free permeate stream and a highly concentrated solids stream. This is a crosscutting technology that falls under the Efficient Separations and Processing Crosscutting Program, with potential application to tank wastes, contaminated groundwater, landfill leachate, and secondary liquid waste streams from other remediation processes, including decontamination and decommissioning systems. SpinTek II High Shear Rotary Membrane Filtration System is a unique compact crossflow membrane system that has large, demonstrable advantages in performance and cost compared to currently available systems: (1) High fluid shear prevents membrane fouling even with very high solids content; hazardous and radioactive components can be concentrated to the consistency of a pasty slurry without fouling. (2) Induced turbulence and shear across the membrane increases membrane flux by a factor of ten over existing systems and allows operation on fluids not otherwise treatable. (3) Innovative ceramic membrane and mechanical sealing technology eliminates compatibility problems with aggressive DOE waste streams. (4) System design allows rapid, simple disassembly for inspection or complete decontamination. (5) Produces colloidal- and suspended-solids-free filtrate without the addition of chemicals. The first phase of this project (PRDA maturity stage 5) completed the physical scale-up of the SpinTek unit and verified successful scale-up with surrogate materials. Given successful scale-up and DOE concurrence, the second phase of this project (PRDA maturity stage 6) will provide for the installation and

  20. Gallium 67 scintigraphy in glomerular disease

    SciTech Connect

    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.

  1. A PERSPECTIVE OF RIVERBANK FILTRATION

    EPA Science Inventory

    Riverbank filtration is a process in which pumping of wells located along riverbanks induce a portion of the river water to flow toward the pumping wells. The process has many similarities to the slow sand filtration process. River water contaminants are attenuated due to a combi...

  2. MICROBIOLOGY AND DRINKING WATER FILTRATION

    EPA Science Inventory

    Concerns about waterborne viruses and protozoan cysts developed in the third quarter of the twentieth century, and filtration research for microorganism control in the 1960's through 1980's has reflected these concerns. The chapter briefly reviews historical filtration research f...

  3. Glycosaminoglycan Regulation by VEGFA and VEGFC of the Glomerular Microvascular Endothelial Cell Glycocalyx in Vitro

    PubMed Central

    Foster, Rebecca R.; Armstrong, Lynne; Baker, Siân; Wong, Dickson W.L.; Wylie, Emma C.; Ramnath, Raina; Jenkins, Robert; Singh, Anurag; Steadman, Robert; Welsh, Gavin I.; Mathieson, Peter W.; Satchell, Simon C.

    2014-01-01

    Damage to endothelial glycocalyx impairs vascular barrier function and may contribute to progression of chronic vascular disease. An early indicator is microalbuminuria resulting from glomerular filtration barrier damage. We investigated the contributions of hyaluronic acid (HA) and chondroitin sulfate (CS) to glomerular microvascular endothelial cell (GEnC) glycocalyx and examined whether these are modified by vascular endothelial growth factors A and C (VEGFA and VEGFC). HA and CS were imaged on GEnCs and their resynthesis was examined. The effect of HA and CS on transendothelial electrical resistance (TEER) and labeled albumin flux across monolayers was assessed. Effects of VEGFA and VEGFC on production and charge characteristics of glycosaminoglycan (GAG) were examined via metabolic labeling and liquid chromatography. GAG shedding was quantified using Alcian Blue. NDST2 expression was examined using real-time PCR. GEnCs expressed HA and CS in the glycocalyx. CS contributed to the barrier to both ion (TEER) and protein flux across the monolayer; HA had only a limited effect. VEGFC promoted HA synthesis and increased the charge density of synthesized GAGs. In contrast, VEGFA induced shedding of charged GAGs. CS plays a role in restriction of macromolecular flux across GEnC monolayers, and VEGFA and VEGFC differentially regulate synthesis, charge, and shedding of GAGs in GEnCs. These observations have important implications for endothelial barrier regulation in glomerular and other microvascular beds. PMID:23770346

  4. Glomerular Polycystic Kidney Disease in a Dog (Blue Merle Collie)

    PubMed Central

    Chalifoux, A.; Phaneuf, J. -B.; Olivieri, M.; Gosselin, Y.

    1982-01-01

    Glomerular polycystic kidney disease was diagnosed in an 11 month old, female, Blue Merle Collie. Clinical signs (polyuria, polydipsia, vomiting, diarrhea, partial anorexia) and laboratory work (blood urea nitrogen, creatinine, serum phosphorus, specific gravity, proteinuria, nonregenerative anemia) indicated chronic renal failure. However, after the study of a biopsy specimen, a definitive diagnosis was reached and the prognosis was determined. Necropsy findings and histopathological studies revealed: presence of glomerular cysts, atrophy of glomerular tufts and sclerosis of the interstitial tissue. ImagesFigure 1.Figure 2.Figure 3.Figure 4. PMID:17422209

  5. PILOT PLANT EXPLORATION OF SLOW RATE FILTRATION

    EPA Science Inventory

    Alternatives to conventional coagulation water filtration plants (those that utilize coagulation, flocculation, sedimentation and filtration) may be appropriate for some small water utilities. One such alternative is slow rate filtration. This paper describes pilot plant studies ...

  6. A flexible, multilayered protein scaffold maintains the slit in between glomerular podocytes

    PubMed Central

    Grahammer, Florian; Wigge, Christoph; Schell, Christoph; Kretz, Oliver; Patrakka, Jaakko; Schneider, Simon; Klose, Martin; Arnold, Sebastian J.; Habermann, Anja; Bräuniger, Ricarda; Rinschen, Markus M.; Völker, Linus; Bregenzer, Andreas; Rubbenstroth, Dennis; Boerries, Melanie; Kerjaschki, Dontscho; Miner, Jeffrey H.; Walz, Gerd; Benzing, Thomas; Fornoni, Alessia; Frangakis, Achilleas S.; Huber, Tobias B.

    2016-01-01

    Vertebrate life critically depends on renal filtration and excretion of low molecular weight waste products. This process is controlled by a specialized cell-cell contact between podocyte foot processes: the slit diaphragm (SD). Using a comprehensive set of targeted KO mice of key SD molecules, we provided genetic, functional, and high-resolution ultrastructural data highlighting a concept of a flexible, dynamic, and multilayered architecture of the SD. Our data indicate that the mammalian SD is composed of NEPHRIN and NEPH1 molecules, while NEPH2 and NEPH3 do not participate in podocyte intercellular junction formation. Unexpectedly, homo- and heteromeric NEPHRIN/NEPH1 complexes are rarely observed. Instead, single NEPH1 molecules appear to form the lower part of the junction close to the glomerular basement membrane with a width of 23 nm, while single NEPHRIN molecules form an adjacent junction more apically with a width of 45 nm. In both cases, the molecules are quasiperiodically spaced 7 nm apart. These structural findings, in combination with the flexibility inherent to the repetitive Ig folds of NEPHRIN and NEPH1, indicate that the SD likely represents a highly dynamic cell-cell contact that forms an adjustable, nonclogging barrier within the renal filtration apparatus. PMID:27430022

  7. Health Benefits of Particle Filtration

    SciTech Connect

    Fisk, William J.

    2013-10-01

    The evidence of health benefits of particle filtration in homes and commercial buildings is reviewed. Prior reviews of papers published before 2000 are summarized. The results of 16 more recent intervention studies are compiled and analyzed. Also reviewed are four studies that modeled health benefits of using filtration to reduce indoor exposures to particles from outdoors. Prior reviews generally concluded that particle filtration is, at best, a source of small improvements in allergy and asthma health effects; however, many early studies had weak designs. A majority of recent intervention studies employed strong designs and more of these studies report statistically significant improvements in health symptoms or objective health outcomes, particularly for subjects with allergies or asthma. The percentage improvement in health outcomes is typically modest, e.g., 7percent to 25percent. Delivery of filtered air to the breathing zone of sleeping allergic or asthmatic persons may be more consistently effective in improving health than room air filtration. Notable are two studies that report statistically significant improvements, with filtration, in markers that predict future adverse coronary events. From modeling, the largest potential benefits of indoor particle filtration may be reductions in morbidity and mortality from reducing indoor exposures to particles from outdoor air.

  8. Health Benefits of Particle Filtration

    SciTech Connect

    Fisk, William J.

    2013-10-01

    The evidence of health benefits of particle filtration in homes and commercial buildings is reviewed. Prior reviews of papers published before 2000 are summarized. The results of 16 more recent intervention studies are compiled and analyzed. Also, reviewed are four studies that modeled health benefits of using filtration to reduce indoor exposures to particles from outdoors. Prior reviews generally concluded that particle filtration is, at best, a source of small improvements in allergy and asthma health effects; however, many early studies had weak designs. A majority of recent intervention studies employed strong designs and more of these studies report statistically significant improvements in health symptoms or objective health outcomes, particularly for subjects with allergies or asthma. The percent age improvement in health outcomes is typically modest, for example, 7percent to 25percent. Delivery of filtered air to the breathing zone of sleeping allergic or asthmatic persons may be more consistently effective in improving health than room air filtration. Notable are two studies that report statistically significant improvements, with filtration, in markers that predict future adverse coronary events. From modeling, the largest potential benefits of indoor particle filtration may be reductions in morbidity and mortality from reducing indoor exposures to particles from outdoor air.

  9. Prevalence of asymptomatic urinary abnormalities among adolescents.

    PubMed

    Fouad, Mohamed; Boraie, Maher

    2016-05-01

    To determine the prevalence of asymptomatic urinary abnormalities in adolescents, first morning clean mid-stream urine specimens were obtained from 2500 individuals and examined by dipstick and light microscopy. Adolescents with abnormal screening results were reexamined after two weeks and those who had abnormal results twice were subjected to systemic clinical examination and further clinical and laboratory investigations. Eight hundred and three (32.1%) individuals had urinary abnormalities at the first screening, which significantly decreased to 345 (13.8%) at the second screening, (P <0.001). Hematuria was the most common urinary abnormalities detected in 245 (9.8%) adolescents who had persistent urine abnormalities; 228 (9.1%) individuals had non glomerular hematuria. The hematuria was isolated in 150 (6%) individuals, combined with leukocyturia in 83 (3.3%) individuals, and combined with proteinuria in 12 (0.5%) individuals. Leukocyturia was detected in 150 (6%) of all studied adolescents; it was isolated in 39 (1.6%) individuals and combined with proteinuria in 28 (1.1%) of them. Asymptomatic bacteriuria was detected in 23 (0.9%) of all studied adolescents; all the cases were females. Proteinuria was detected in 65 (2.6%) of all the studied adolescents; 45 (1.8%) individuals had <0.5 g/day and twenty (0.8%) individuals had 0.5-3 g/day. Asymptomatic urinary abnormalities were more common in males than females and adolescents from rural than urban areas (P <0.01) and (P <0.001), respectively. The present study found a high prevalence of asymptomatic urinary abnormalities among adolescents in our population. PMID:27215241

  10. Gq signaling causes glomerular injury by activating TRPC6

    PubMed Central

    Wang, Liming; Jirka, Grant; Rosenberg, Paul B.; Buckley, Anne F.; Gomez, Jose A.; Fields, Timothy A.; Winn, Michelle P.; Spurney, Robert F.

    2015-01-01

    Familial forms of focal segmental glomerulosclerosis (FSGS) have been linked to gain-of-function mutations in the gene encoding the transient receptor potential channel C6 (TRPC6). GPCRs coupled to Gq signaling activate TRPC6, suggesting that Gq-dependent TRPC6 activation underlies glomerular diseases. Here, we developed a murine model in which a constitutively active Gq α subunit (GqQ209L, referred to herein as GqQ>L) is specifically expressed in podocytes and examined the effects of this mutation in response to puromycin aminonucleoside (PAN) nephrosis. We found that compared with control animals, animals expressing GqQ>L exhibited robust albuminuria, structural features of FSGS, and reduced numbers of glomerular podocytes. Gq activation stimulated calcineurin (CN) activity, resulting in CN-dependent upregulation of TRPC6 in murine kidneys. Deletion of TRPC6 in GqQ>L-expressing mice prevented FSGS development and inhibited both tubular damage and podocyte loss induced by PAN nephrosis. Similarly, administration of the CN inhibitor FK506 reduced proteinuria and tubular injury but had more modest effects on glomerular pathology and podocyte numbers in animals with constitutive Gq activation. Moreover, these Gq-dependent effects on podocyte injury were generalizable to diabetic kidney disease, as expression of GqQ>L promoted albuminuria, mesangial expansion, and increased glomerular basement membrane width in diabetic mice. Together, these results suggest that targeting Gq/TRPC6 signaling may have therapeutic benefits for the treatment of glomerular diseases. PMID:25844902

  11. Podometrics as a potential clinical tool for glomerular disease management

    PubMed Central

    Kikuchi, Masao; Wickman, Larysa; Hodgin, JB; Wiggins, Roger C.

    2015-01-01

    Chronic Kidney Disease culminating in End Stage Kidney Disease is a major public health problem costing in excess of $40 billion per year with high morbidity and mortality. Current tools for glomerular disease monitoring lack precision and contribute to poor outcome. The podocyte depletion hypothesis describes the major mechanisms underlying progression of glomerular diseases responsible for >80% of ESKD. The question arises whether this new knowledge can be used to improve outcomes and reduce costs. Podocytes have unique characteristics that make them an attractive monitoring tool. Methodologies for estimating podocyte number, size, density, glomerular volume and other parameters in routine kidney biopsies, and the rate of podocyte detachment from glomeruli into urine (“podometrics”), have now been developed and validated. They potentially fill important gaps in the glomerular disease monitoring toolbox. Application of these tools to glomerular disease groups demonstrates good correlation with outcome, although data validating their use for individual decision-making is not yet available. Given the urgency of the clinical problem we argue that the time has come to focus on testing these tools for application to individualized clinical decision-making towards more effective progression prevention. PMID:26215862

  12. Filtration: An investment in IAQ

    SciTech Connect

    Burroughs, H.E.B.

    1997-08-01

    Air filtration is a forgotten component in the resiliency engineering equation. This under-utilized asset is becoming more understandable and user-friendly, bringing about giant strides in application technology in commercial buildings for IAQ resiliency. Filtration and air cleaning are highly developed and well-established technologies in industrial and specialized application areas. These include a variety of clean room applications as well as a wide array of highly sophisticated industrial needs for varying degrees and types of cleansed air sources. Application areas include pharmaceutical, health care, process control, and electronic protection, to name a few. Yet filtration generally remains an under-utilized technology in the field of indoor environmental quality in commercial buildings. Although source control is clearly the preferred technique for controlling air contaminants, air cleaning can provide a spectrum of valuable and cost-effective tactics to achieve and maintain an acceptable indoor environment.

  13. Reduced Krüppel-Like Factor 2 Aggravates Glomerular Endothelial Cell Injury and Kidney Disease in Mice with Unilateral Nephrectomy.

    PubMed

    Zhong, Fang; Mallipattu, Sandeep K; Estrada, Chelsea; Menon, Madhav; Salem, Fadi; Jain, Mukesh K; Chen, Hongyu; Wang, Yongjun; Lee, Kyung; He, John C

    2016-08-01

    Loss of functional nephrons induces compensatory glomerular hyperfiltration and hypertrophy, leading to the progression of chronic kidney disease. Krüppel-like factor 2 (KLF2), a shear-stress-inducible transcription factor, confers protection against endothelial injury. Because glomerular hyperfiltration is associated with shear stress, we hypothesized that KLF2 may be an important factor in the compensatory response to unilateral nephrectomy (UNX). To test this hypothesis, endothelial cell-specific Klf2 heterozygous knockout mice (KO) and their wild-type littermate control (WT) underwent either UNX or sham-operation. WT-UNX mice developed compensatory renal hypertrophy as expected, whereas KO-UNX mice did not. KO-UNX mice exhibited higher blood pressure, reduced glomerular filtration rate, and significant increase in proteinuria and glomerulosclerosis compared to WT-UNX. Expression of endothelial nitric oxide synthase (official name Nos3), a known transcriptional target gene of KLF2, was significantly reduced and dysregulation of other endothelial genes was also observed in the glomeruli of KO-UNX when compared to WT-UNX and sham-operated mice. Furthermore, both podocyte number and expression of podocyte markers were also significantly reduced in KO-UNX glomeruli, indicating a potential cross talk between glomerular endothelial cells and podocytes. Finally, decreased renal expression of KLF2 in nephrectomy patients was associated with the progression of kidney disease. Taken together, our data demonstrate a protective role of KLF2 against glomerular endothelial cell injury and progression of chronic kidney disease in the model of compensatory renal hypertrophy. PMID:27317905

  14. Abnormalities of endothelial function in patients with predialysis renal failure

    PubMed Central

    Thambyrajah, J; Landray, M; McGlynn, F; Jones, H; Wheeler, D; Townend, J

    2000-01-01

    BACKGROUND—Endothelial dysfunction plays an important role in the development of atherosclerotic vascular disease, which is the leading cause of mortality in patients with chronic renal failure.
OBJECTIVE—To examine the relation between predialysis renal failure and endothelial function.
DESIGN—Two groups were studied: 80 patients with non-diabetic chronic renal failure and 26 healthy controls, with similar age and sex distributions. Two indices of endothelial function were assessed: high resolution ultrasonography to measure flow mediated endothelium dependent dilatation of the brachial artery following reactive hyperaemia, and plasma concentration of von Willebrand factor. Endothelium independent dilatation was also assessed following sublingual glyceryl trinitrate. The patients were divided into those with and without overt atherosclerotic vascular disease.
RESULTS—Although patients with chronic renal failure had significantly impaired endothelium dependent dilatation compared with controls (median (interquartile range), 2.6% (0.7% to 4.8%) v 6.5% (4.8% to 8.3%); p < 0.001) and increased von Willebrand factor (254 (207 to 294) v 106 (87 to 138) iu/dl; p < 0.001), there was no difference between renal failure patients with and without atherosclerotic vascular disease. Within the chronic renal failure group, endothelium dependent dilatation and von Willebrand factor were similar in patients in the upper and lower quartiles of glomerular filtration rate (2.7% (0.7% to 6.7%) v 2.8% (1.1% to 5.0%); and 255 (205 to 291) v 254 (209 to 292) iu/dl, respectively). Endothelium independent dilatation did not differ between the renal failure or control groups and was also similar in patients with renal failure irrespective of the degree of renal failure or the presence of atherosclerotic vascular disease.
CONCLUSIONS—Endothelial function is abnormal in chronic renal failure, even in patients with mild renal insufficiency and those without

  15. Immunology of anti-glomerular basement membrane disease.

    PubMed

    Salama, Alan D; Pusey, Charles D

    2002-05-01

    Anti-glomerular basement membrane disease is a form of autoimmune glomerulonephritis often accompanied by lung haemorrhage. It is characterized by circulating and deposited antibodies that bind basement membrane components in the glomerulus and lung alveolus. Since early descriptions of the deposition of immunoglobulin on the glomerular basement membrane, work has focused on the binding properties of the autoantibodies, and this has led to the identification of the autoantigen as the non-collagenous region of the alpha 3 chain of type IV collagen. Despite being thought of as a prototypic antibody mediated autoimmune disease, it is becoming apparent that both humoral and cellular immune mechanisms act in concert to initiate and perpetuate disease. Recent data have shed light on the molecular pathogenesis of anti-glomerular basement membrane disease and provided a more complete framework on which to build our understanding of autoimmune renal disease. This should lead to novel approaches to immunotherapy for patients with glomerulonephritis. PMID:11981257

  16. Filtrates and Residues: Gel Filtration--An Innovative Separation Technique.

    ERIC Educational Resources Information Center

    Blumenfeld, Fred; Gardner, James

    1985-01-01

    Gel filtration is a form of liquid chromatography that separates molecules primarily on the basis of their size. Advantages of using this technique, theoretical aspects, and experiments (including procedures used) are discussed. Several questions for students to answer (with answers) are also provided. (JN)

  17. Integrated pore blockage-cake filtration model for crossflow filtration

    SciTech Connect

    Daniel, Richard C.; Billing, Justin M.; Russell, Renee L.; Shimskey, Rick W.; Smith, Harry D.; Peterson, Reid A.

    2011-07-01

    Crossflow filtration is to be a key process in the treatment and disposal of approximately 60,000 metric tons of high-level radioactive waste stored at the Hanford Site in Richland, Washington. Pacific Northwest National Laboratory is assessing filter performance with waste simulant materials that mimic the chemical and physical properties of Hanford tank waste. Prior simulant studies indicated that waste filtration performance may be limited by pore and cake fouling. To limit the shutdown of waste treatment operations, the pre-treatment facility plans to recover filter flux losses from cake formation and filter fouling by frequently backpulsing the filter elements. The objective of the current paper is to develop a simple model of flux decline resulting from cake and pore fouling and potential flux recovery through backpulsing of the filters for Hanford waste filtration operations. To this end, a model capable of characterizing the decline in waste-simulant filter flux as a function of both irreversible pore blockage and reversible cake formation is proposed. This model is used to characterize the filtration behavior of Hanford waste simulants in both continuous and backpulsed operations. The model is then used to infer the optimal backpulse frequency under specific operating conditions.

  18. Neonatal Fc receptor promotes immune complex-mediated glomerular disease.

    PubMed

    Olaru, Florina; Luo, Wentian; Suleiman, Hani; St John, Patricia L; Ge, Linna; Mezo, Adam R; Shaw, Andrey S; Abrahamson, Dale R; Miner, Jeffrey H; Borza, Dorin-Bogdan

    2014-05-01

    The neonatal Fc receptor (FcRn) is a major regulator of IgG and albumin homeostasis systemically and in the kidneys. We investigated the role of FcRn in the development of immune complex-mediated glomerular disease in mice. C57Bl/6 mice immunized with the noncollagenous domain of the α3 chain of type IV collagen (α3NC1) developed albuminuria associated with granular capillary loop deposition of exogenous antigen, mouse IgG, C3 and C5b-9, and podocyte injury. High-resolution imaging showed abundant IgG deposition in the expanded glomerular basement membrane, especially in regions corresponding to subepithelial electron dense deposits. FcRn-null and -humanized mice immunized with α3NC1 developed no albuminuria and had lower levels of serum IgG anti-α3NC1 antibodies and reduced glomerular deposition of IgG, antigen, and complement. Our results show that FcRn promotes the formation of subepithelial immune complexes and subsequent glomerular pathology leading to proteinuria, potentially by maintaining higher serum levels of pathogenic IgG antibodies. Therefore, reducing pathogenic IgG levels by pharmacologic inhibition of FcRn may provide a novel approach for the treatment of immune complex-mediated glomerular diseases. As proof of concept, we showed that a peptide inhibiting the interaction between human FcRn and human IgG accelerated the degradation of human IgG anti-α3NC1 autoantibodies injected into FCRN-humanized mice as effectively as genetic ablation of FcRn, thus preventing the glomerular deposition of immune complexes containing human IgG. PMID:24357670

  19. Neonatal Fc Receptor Promotes Immune Complex–Mediated Glomerular Disease

    PubMed Central

    Olaru, Florina; Luo, Wentian; Suleiman, Hani; St. John, Patricia L.; Ge, Linna; Mezo, Adam R.; Shaw, Andrey S.; Abrahamson, Dale R.; Miner, Jeffrey H.

    2014-01-01

    The neonatal Fc receptor (FcRn) is a major regulator of IgG and albumin homeostasis systemically and in the kidneys. We investigated the role of FcRn in the development of immune complex–mediated glomerular disease in mice. C57Bl/6 mice immunized with the noncollagenous domain of the α3 chain of type IV collagen (α3NC1) developed albuminuria associated with granular capillary loop deposition of exogenous antigen, mouse IgG, C3 and C5b-9, and podocyte injury. High-resolution imaging showed abundant IgG deposition in the expanded glomerular basement membrane, especially in regions corresponding to subepithelial electron dense deposits. FcRn-null and -humanized mice immunized with α3NC1 developed no albuminuria and had lower levels of serum IgG anti-α3NC1 antibodies and reduced glomerular deposition of IgG, antigen, and complement. Our results show that FcRn promotes the formation of subepithelial immune complexes and subsequent glomerular pathology leading to proteinuria, potentially by maintaining higher serum levels of pathogenic IgG antibodies. Therefore, reducing pathogenic IgG levels by pharmacologic inhibition of FcRn may provide a novel approach for the treatment of immune complex–mediated glomerular diseases. As proof of concept, we showed that a peptide inhibiting the interaction between human FcRn and human IgG accelerated the degradation of human IgG anti-α3NC1 autoantibodies injected into FCRN-humanized mice as effectively as genetic ablation of FcRn, thus preventing the glomerular deposition of immune complexes containing human IgG. PMID:24357670

  20. Tumor necrosis factor induces glomerular damage in the rabbit.

    PubMed Central

    Bertani, T.; Abbate, M.; Zoja, C.; Corna, D.; Perico, N.; Ghezzi, P.; Remuzzi, G.

    1989-01-01

    Tumor necrosis factor (TNF) is a polypeptide hormone produced by activated macrophages detectable in the circulation of experimental animals given endotoxin. Recent evidence strongly suggests that many of the deleterious effects of endotoxin in experimental animals are mediated by TNF. Because endotoxemia in experimental animals and humans is associated with glomerular damage the present investigation was designed to establish whether TNF directly induces glomerular functional and structural changes. Twenty-three rabbits were given human recombinant TNF at the doses of 0.08, 0.8, and 8.0 micrograms/kg/h as a continuous 5-hour intravenous infusion. Animals were killed at the end of the infusion. All rabbits given 0.8 and 8.0 micrograms/kg/h TNF developed anemia (Ht value decrease at 5 hours: 0.8 microgram/kg/h, 15%; 8.0 micrograms/kg/h, 16%); leukopenia (leukocyte count decrease at 5 hours: 0.8 micrograms/kg/h, 47%; 8.0 micrograms/kg/h, 59%); thrombocytopenia (platelet count decrease at 5 hours; 0.8 micrograms/kg/h, 45%; 8.0 micrograms/kg/h, 57%). Rabbits given 8.0 micrograms/kg/h also had renal failure (serum creatinine from 1.02 +/- 0.15 to 1.64 +/- 0.34 mg/dl). By light microscopy only occasional polymorphonuclear leukocytes in the glomerular capillaries were detectable in rabbits infused with 0.08 micrograms/kg/h TNF, whereas with 0.8 micrograms/kg/h TNF the presence of inflammatory cells in the glomerular capillaries was the prominent finding. With 8.0 micrograms/kg/h TNF beside leukocyte accumulation, fibrin was detected in the glomerular capillary lumens of two of eight animals. Electron microscopy found dose-dependent glomerular endothelial cell damage in animals given TNF with fibrinlike material in the capillary lumens. Glomerular changes induced by TNF were remarkably similar to those previously found in animals given endotoxin. Thus, TNF is likely to be the mediator of endotoxin-induced glomerular damage and can be regarded as a new mediator of

  1. Comparison of different normalization strategies for the analysis of glomerular microRNAs in IgA nephropathy

    PubMed Central

    Bockmeyer, Clemens L.; Säuberlich, Karen; Wittig, Juliane; Eßer, Marc; Roeder, Sebastian S.; Vester, Udo; Hoyer, Peter F.; Agustian, Putri A.; Zeuschner, Philip; Amann, Kerstin; Daniel, Christoph; Becker, Jan U.

    2016-01-01

    Small nucleolar RNAs (snoRNAs) have been used for normalization in glomerular microRNA (miRNA) quantification without confirmation of validity. Our aim was to identify glomerular reference miRNAs in IgA nephropathy. We compared miRNAs in human paraffin-embedded renal biopsies from patients with cellular-crescentic IgA-GN (n = 5; crescentic IgA-GN) and non-crescentic IgA-GN (n = 5; IgA-GN) to mild interstitial nephritis without glomerular abnormalities (controls, n = 5). Laser-microdissected glomeruli were used for expression profiling of 762 miRNAs by low-density TaqMan arrays (cards A and B). The comparison of different normalization methods (GeNormPlus, NormFinder, global mean and snoRNAs) in crescentic IgA-GN, IgA-GN and controls yielded similar results. However, levels of significance and the range of relative expression differed. In median, two normalization methods demonstrated similar results. GeNormPlus and NormFinder gave different top ranked reference miRNAs. Stability ranking for snoRNAs varied between cards A and B. In conclusion, we suggest the geometric mean of the most stable reference miRNAs found in GeNormPlus (miR-26b-5p), NormFinder (miR-28-5p) and snoRNAs (RNU44) as reference. It should be considered that significant differences could be missed using one particular normalization method. As a starting point for glomerular miRNA studies in IgA nephropathy we provide a library of miRNAs. PMID:27553688

  2. Improving IAQ Via Air Filtration.

    ERIC Educational Resources Information Center

    Monk, Brian

    1999-01-01

    Provides tips on using air filtration to control indoor air quality in educational facilities, including dedicated spaces with unique air quality conditions such as in libraries, museums and archival storage areas, kitchens and dining areas, and laboratories. The control of particulate contaminants, gaseous contaminants, and moisture buildup are…

  3. Filtration combustion: Smoldering and SHS

    NASA Technical Reports Server (NTRS)

    Matkowsky, Bernard J.

    1995-01-01

    Smolder waves and SHS (self-propagating high-temperature synthesis) waves are both examples of combustion waves propagating in porous media. When delivery of reactants through the pores to the reaction site is an important aspect of the process, it is referred to as filtration combustion. The two types of filtration combustion have a similar mathematical formulation, describing the ignition, propagation and extinction of combustion waves in porous media. The goal in each case, however, is different. In smoldering the desired goal is to prevent propagation, whereas in SHS the goal is to insure propagation of the combustion wave, leading to the synthesis of desired products. In addition, the scales in the two areas of application may well differ. For example, smoldering generally occurs at a relatively low temperature and with a smaller propagation velocity than SHS filtration combustion waves. Nevertheless, the two areas of application have much in common, so that mechanisms learned about in one application can be used to advantage in the other. In this paper we discuss recent results in the areas of filtration combustion.

  4. ELECTROSTATIC STIMULATION OF FABRIC FILTRATION

    EPA Science Inventory

    The paper gives results of an investigation of the concept of electrostatic stimulation of fabric filtration (ESFF) at pilot scale. The pilot unit consisted of a conventional baghouse in parallel with an ESFF baghouse, allowing direct comparison. Reported results are for pulse-cl...

  5. TEST OF FABRIC FILTRATION MATERIALS

    EPA Science Inventory

    The report describes pilot scale and laboratory tests of U.S. and Polish woven baghouse fabrics. Cotton, polyester, aramid, and glass fabrics were tested using cement, flyash, coal, and talc dusts at loadings of about 10 g/cu m, filtration velocities of 60 and 80 cu m/sq m, and a...

  6. MICROBIOLOGICAL REMOVAL BY FILTRATION PROCESSES

    EPA Science Inventory

    Filtration ws originally used to remove contaminants that affect the appearance, odor, and taste of drinking water. Later it was demonstrated that bacteria in drinking water were causative agents of disease. Water treatment technology improved with the addition of disinfection, c...

  7. Health benefits of particle filtration

    EPA Science Inventory

    This product was developed under an interagency agreement between the U.S. EPA and the U.S. Department of Energy - Lawrence Berkeley National Laboratory (LBNL). The evidence of health benefits of particle filtration in homes and commercial buildings is reviewed. Prior reviews o...

  8. ITP Filtrate Benzene Removal Alternatives

    SciTech Connect

    Dworjanyn, L.O.

    1993-05-21

    Existing ITP filtrate hold tanks may provide sufficient capacity and residence time to strip dissolved benzene from the incoming filtrate using nitrogen sparging in the bottom of the old tanks. This is based on equilibrium supported by late Wash test data using aged washed slurry. Theoretical considerations indicate that benzene stripping will be more difficult from the ITP unwashed high salt filtrates due to reduced mass transfer. Therefore experimental sparging data is needed to quantify the theoretical effects.Foaming limits which dictate allowable sparging rate will also have to be established. Sparging in the hold tanks will require installation of sintered metal spargers, and possibly stirrers and foam monitoring/disengagement equipment. The most critical sparging needs are at the start of the precipitation/concentration cycle, when the filtrate flux rate is the highest,and at the end of wash cycle where Henry`s equilibrium constant falls off,requiring more gas to sparge the dissolved benzene. With adequate recycle (for proper distribution) or sparging in the old tanks, the 30 inch column could be used for the complete ITP process. A courser packing would reduce back pressure while enabling benzene stripping. The Late Wash Tests indicate adequate benzene stripping even at reduced gas flow. This will require experimental verification under ITP conditions. Using the 30 in. column vs 18 in. during the wash cycle will enhance stripping without need for additional sparging provided the minimum flow requirements are met.

  9. Filtration device for active effluents

    SciTech Connect

    Guerin, M.; Meunier, G.

    1994-12-31

    Among the various techniques relating to solid/liquid separations, filtration is currently utilized for treating radioactive effluents. After testing different equipments on various simulated effluents, the Valduc Center has decided to substitute a monoplate filter for a rotative diatomite precoated filter.

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

    PubMed

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

    2007-07-01

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

  11. Inhibition of integrin α2β1 ameliorates glomerular injury.

    PubMed

    Borza, Corina M; Su, Yan; Chen, Xiwu; Yu, Ling; Mont, Stacey; Chetyrkin, Sergei; Voziyan, Paul; Hudson, Billy G; Billings, Paul C; Jo, Hyunil; Bennett, Joel S; Degrado, William F; Eckes, Beate; Zent, Roy; Pozzi, Ambra

    2012-06-01

    Mesangial cells and podocytes express integrins α1β1 and α2β1, which are the two major collagen receptors that regulate multiple cellular functions, including extracellular matrix homeostasis. Integrin α1β1 protects from glomerular injury by negatively regulating collagen production, but the role of integrin α2β1 in renal injury is unclear. Here, we subjected wild-type and integrin α2-null mice to injury with adriamycin or partial renal ablation. In both of these models, integrin α2-null mice developed significantly less proteinuria and glomerulosclerosis. In addition, selective pharmacological inhibition of integrin α2β1 significantly reduced adriamycin-induced proteinuria, glomerular injury, and collagen deposition in wild-type mice. This inhibitor significantly reduced collagen synthesis in wild-type, but not integrin α2-null, mesangial cells in vitro, demonstrating that its effects are integrin α2β1-dependent. Taken together, these results indicate that integrin α2β1 contributes to glomerular injury by positively regulating collagen synthesis and suggest that its inhibition may be a promising strategy to reduce glomerular injury and proteinuria. PMID:22440900

  12. Inhibition of Integrin α2β1 Ameliorates Glomerular Injury

    PubMed Central

    Borza, Corina M.; Su, Yan; Chen, Xiwu; Yu, Ling; Mont, Stacey; Chetyrkin, Sergei; Voziyan, Paul; Hudson, Billy G.; Billings, Paul C.; Jo, Hyunil; Bennett, Joel S.; DeGrado, William F.; Eckes, Beate; Zent, Roy

    2012-01-01

    Mesangial cells and podocytes express integrins α1β1 and α2β1, which are the two major collagen receptors that regulate multiple cellular functions, including extracellular matrix homeostasis. Integrin α1β1 protects from glomerular injury by negatively regulating collagen production, but the role of integrin α2β1 in renal injury is unclear. Here, we subjected wild-type and integrin α2-null mice to injury with adriamycin or partial renal ablation. In both of these models, integrin α2-null mice developed significantly less proteinuria and glomerulosclerosis. In addition, selective pharmacological inhibition of integrin α2β1 significantly reduced adriamycin-induced proteinuria, glomerular injury, and collagen deposition in wild-type mice. This inhibitor significantly reduced collagen synthesis in wild-type, but not integrin α2-null, mesangial cells in vitro, demonstrating that its effects are integrin α2β1-dependent. Taken together, these results indicate that integrin α2β1 contributes to glomerular injury by positively regulating collagen synthesis and suggest that its inhibition may be a promising strategy to reduce glomerular injury and proteinuria. PMID:22440900

  13. Renin lineage cells repopulate the glomerular mesangium after injury.

    PubMed

    Starke, Charlotte; Betz, Hannah; Hickmann, Linda; Lachmann, Peter; Neubauer, Björn; Kopp, Jeffrey B; Sequeira-Lopez, Maria Luisa S; Gomez, R Ariel; Hohenstein, Bernd; Todorov, Vladimir T; Hugo, Christian P M

    2015-01-01

    Mesangial cell injury has a major role in many CKDs. Because renin-positive precursor cells give rise to mesangial cells during nephrogenesis, this study tested the hypothesis that the same phenomenon contributes to glomerular regeneration after murine experimental mesangial injury. Mesangiolysis was induced by administration of an anti-mesangial cell serum in combination with LPS. In enhanced green fluorescent protein-reporter mice with constitutively labeled renin lineage cells, the size of the enhanced green fluorescent protein-positive area in the glomerular tufts increased after mesangial injury. Furthermore, we generated a novel Tet-on inducible triple-transgenic LacZ reporter line that allowed selective labeling of renin cells along renal afferent arterioles of adult mice. Although no intraglomerular LacZ expression was detected in healthy mice, about two-thirds of the glomerular tufts became LacZ positive during the regenerative phase after severe mesangial injury. Intraglomerular renin descendant LacZ-expressing cells colocalized with mesangial cell markers α8-integrin and PDGF receptor-β but not with endothelial, podocyte, or parietal epithelial cell markers. In contrast with LacZ-positive cells in the afferent arterioles, LacZ-positive cells in the glomerular tuft did not express renin. These data demonstrate that extraglomerular renin lineage cells represent a major source of repopulating cells for reconstitution of the intraglomerular mesangium after injury. PMID:24904091

  14. IgM Contributes to Glomerular Injury in FSGS

    PubMed Central

    Strassheim, Derek; Renner, Brandon; Panzer, Sarah; Fuquay, Richard; Kulik, Liudmila; Ljubanović, Danica; Holers, V. Michael

    2013-01-01

    Glomerular IgM and C3 deposits frequently accompany idiopathic FSGS and secondary glomerulosclerosis, but it is unknown whether IgM activates complement, possibly contributing to the pathogenesis of these diseases. We hypothesized that IgM natural antibody binds to neoepitopes exposed in the glomerulus after nonimmune insults, triggering activation of the complement system and further injury. We examined the effects of depleting B cells, using three different strategies, on adriamycin-induced glomerulosclerosis. First, we treated wild-type mice with an anti-murine CD20 antibody, which depletes B cells, before disease induction. Second, we evaluated adriamycin-induced glomerulosclerosis in Jh mice, a strain that lacks mature B cells. Third, we locally depleted peritoneal B cells via hypotonic shock before disease induction. All three strategies reduced deposition of IgM in the glomerulus after administration of adriamycin and attenuated the development of albuminuria. Furthermore, we found that glomerular IgM and C3 were detectable in a subset of patients with FSGS; C3 was present as an activation fragment and colocalized with glomerular IgM, suggesting that glomerular IgM may have bound a cognate ligand. Taken together, these results suggest that IgM activates the complement system within the glomerulus in an animal model of glomerulosclerosis. Strategies that reduce IgM natural antibody or that prevent complement activation may slow the progression of glomerulosclerosis. PMID:23393315

  15. Filtration Understanding: FY10 Testing Results and Filtration Model Update

    SciTech Connect

    Daniel, Richard C.; Billing, Justin M.; Burns, Carolyn A.; Peterson, Reid A.; Russell, Renee L.; Schonewill, Philip P.; Shimskey, Rick W.

    2011-04-04

    This document completes the requirements of Milestone 2-4, Final Report of FY10 Testing, discussed in the scope of work outlined in the EM31 task plan WP-2.3.6-2010-1. The focus of task WP 2.3.6 is to improve the U.S. Department of Energy’s (DOE’s) understanding of filtration operations for high-level waste (HLW) to improve filtration and cleaning efficiencies, thereby increasing process throughput and reducing the Na demand (through acid neutralization). Developing the cleaning/backpulsing requirements will produce much more efficient operations for both the Hanford Tank Waste Treatment and Immobilization Plant (WTP) and the Savannah River Site (SRS), thereby significantly increasing throughput by limiting cleaning cycles. The scope of this work is to develop the understanding of filter fouling to allow developing this cleaning/backpulsing strategy.

  16. WATER FILTRATION FOR ASBESTOS FIBER REMOVAL

    EPA Science Inventory

    This report presents a comprehensive review of data on removal of asbestos fibers by granular media filtration and diatomaceous earth filtration. It summarizes data obtained in pilot plant studies at Duluth and Seattle, in research program carried out at Duluth's Lakewood filtrat...

  17. 40 CFR 141.73 - Filtration.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 24 2013-07-01 2013-07-01 false Filtration. 141.73 Section 141.73 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS (CONTINUED) NATIONAL PRIMARY DRINKING WATER REGULATIONS Filtration and Disinfection § 141.73 Filtration. A public water system that uses a surface water source or...

  18. 40 CFR 141.173 - Filtration.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 23 2011-07-01 2011-07-01 false Filtration. 141.173 Section 141.173 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS (CONTINUED) NATIONAL PRIMARY DRINKING WATER REGULATIONS Enhanced Filtration and Disinfection-Systems Serving 10,000 or More People § 141.173 Filtration. A public...

  19. 40 CFR 141.73 - Filtration.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 23 2011-07-01 2011-07-01 false Filtration. 141.73 Section 141.73 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS (CONTINUED) NATIONAL PRIMARY DRINKING WATER REGULATIONS Filtration and Disinfection § 141.73 Filtration. A public water system that uses a surface water source or...

  20. Glomerular Aging and Focal Global Glomerulosclerosis: A Podometric Perspective.

    PubMed

    Hodgin, Jeffrey B; Bitzer, Markus; Wickman, Larysa; Afshinnia, Farsad; Wang, Su Q; O'Connor, Christopher; Yang, Yan; Meadowbrooke, Chrysta; Chowdhury, Mahboob; Kikuchi, Masao; Wiggins, Jocelyn E; Wiggins, Roger C

    2015-12-01

    Kidney aging is associated with an increasing proportion of globally scarred glomeruli, decreasing renal function, and exponentially increasing ESRD prevalence. In model systems, podocyte depletion causes glomerulosclerosis, suggesting age-associated glomerulosclerosis could be caused by a similar mechanism. We measured podocyte number, size, density, and glomerular volume in 89 normal kidney samples from living and deceased kidney donors and normal poles of nephrectomies. Podocyte nuclear density decreased with age due to a combination of decreased podocyte number per glomerulus and increased glomerular volume. Compensatory podocyte cell hypertrophy prevented a change in the proportion of tuft volume occupied by podocytes. Young kidneys had high podocyte reserve (podocyte density >300 per 10(6) µm(3)), but by 70-80 years of age, average podocyte nuclear density decreased to, <100 per 10(6) µm(3), with corresponding podocyte hypertrophy. In older age podocyte detachment rate (urine podocin mRNA-to-creatinine ratio) was higher than at younger ages and podocytes were stressed (increased urine podocin-to-nephrin mRNA ratio). Moreover, in older kidneys, proteinaceous material accumulated in the Bowman space of glomeruli with low podocyte density. In a subset of these glomeruli, mass podocyte detachment events occurred in association with podocytes becoming binucleate (mitotic podocyte catastrophe) and subsequent wrinkling of glomerular capillaries, tuft collapse, and periglomerular fibrosis. In kidneys of young patients with underlying glomerular diseases similar pathologic events were identified in association with focal global glomerulosclerosis. Podocyte density reduction with age may therefore directly lead to focal global glomerulosclerosis, and all progressive glomerular diseases can be considered superimposed accelerators of this underlying process. PMID:26038526

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

    PubMed

    Marini, Mariana Barreto; Rocha, Laura Penna; Machado, Juliana Reis; Ramalho, Fernando Silva; Dos Reis, Marlene Antônia; Corrêa, Rosana Rosa Miranda

    2016-05-01

    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 µm(2); 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) µm(2); P <0.01 and 12210 (7676-26,945) vs. 4183 (3797-7992) µm(2); 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. PMID:27215240

  2. Decreased glomerular basement membrane heparan sulfate proteoglycan in essential hypertension.

    PubMed

    Heintz, B; Stöcker, G; Mrowka, C; Rentz, U; Melzer, H; Stickeler, E; Sieberth, H G; Greiling, H; Haubeck, H D

    1995-03-01

    Heparan sulfate proteoglycans are major components of the glomerular basement membrane and play a key role in the molecular organization and function of the basement membrane. Moreover, their presence is essential for maintenance of the selective permeability of the glomerular basement membrane. Recently, we isolated and characterized a novel small basement membrane-associated heparan sulfate proteoglycan from human aorta and kidney. Partial amino acid sequence data clearly show that this heparan sulfate proteoglycan is distinct from the large basement membrane-associated heparan sulfate proteoglycan (perlecan). Using specific monoclonal antibodies, we have shown that the novel heparan sulfate proteoglycan is located predominantly in the glomerular basement membrane and, to a lesser extent, in the basement membrane of tubuli. Turnover or, in the course of kidney diseases, degradation of heparan sulfate proteoglycan from glomerular basement membranes may lead to urinary excretion of heparan sulfate proteoglycan, which can be measured by a sensitive enzyme immunoassay. The aim of the present study was to analyze whether changes in the structure and function of glomerular basement membranes can be directly detected by measurement of the excretion of a component of this basement membrane, eg, heparan sulfate proteoglycan into urine. The excretion of this small heparan sulfate proteoglycan was compared after physical exercise in normotensive and hypertensive subjects. Normotensive subjects and treated, essential hypertensive patients underwent a standardized workload on a bicycle ergometer. Biochemical characterization of the urinary proteins and heparan sulfate proteoglycan was performed before and 15 and 45 minutes after exercises.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7875766

  3. Nephrology Update: Glomerular Disease in Children.

    PubMed

    Vogt, Beth

    2016-05-01

    Although kidney disease is much less common in children than in adults, clinicians must remain alert for the renal conditions that occur in this population because prompt diagnosis and management are essential. Acute postinfectious glomerulonephritis occurs as an uncommon sequela of streptococcal and other infections. Management is focused on providing supportive measures, including management of fluid-electrolyte imbalance and hypertension, until the patient recovers. Immunoglobulin (Ig) A nephropathy is a primary glomerulonephritis related to abnormal IgA glycosylation. The most common renal issue in children involves recurrent episodes of painless macroscopic hematuria during times of acute infection. Renal involvement occurs in the majority of children with Henoch-Schönlein purpura (HSP), with most experiencing asymptomatic hematuria and low level proteinuria. More severe forms of HSP nephritis, including rapidly progressive glomerulonephritis, may progress to end-stage kidney disease. Nephrotic syndrome commonly is related to steroid-responsive minimal change disease, and follows a course of relapses and remissions over time. However, a minority of children have steroid-resistant disease with potential for poor renal outcome. PMID:27163763

  4. Interaction between alpha 2-adrenergic and angiotensin II systems in the control of glomerular hemodynamics as assessed by renal micropuncture in the rat

    NASA Technical Reports Server (NTRS)

    Thomson, S. C.; Gabbai, F. B.; Tucker, B. J.; Blantz, R. C.

    1992-01-01

    The hypothesis that renal alpha 2 adrenoceptors influence nephron filtration rate (SNGFR) via interaction with angiotensin II (AII) was tested by renal micropuncture. The physical determinants of SNGFR were assessed in adult male Munich Wistar rats 5-7 d after ipsilateral surgical renal denervation (DNX). DNX was performed to isolate inhibitory central and presynaptic alpha 2 adrenoceptors from end-organ receptors within the kidney. Two experimental protocols were employed: one to test whether prior AII receptor blockade with saralasin would alter the glomerular hemodynamic response to alpha 2 adrenoceptor stimulation with the selective agonist B-HT 933 under euvolemic conditions, and the other to test whether B-HT 933 would alter the response to exogenous AII under conditions of plasma volume expansion. In euvolemic rats, B-HT 933 caused SNGFR to decline as the result of a decrease in glomerular ultrafiltration coefficient (LpA), an effect that was blocked by saralasin. After plasma volume expansion, B-HT 933 showed no primary effect on LpA but heightened the response of arterial blood pressure, glomerular transcapillary pressure gradient, and LpA to AII. The parallel results of these converse experiments suggest a complementary interaction between renal alpha 2-adrenergic and AII systems in the control of LpA.

  5. Centrifugal membrane filtration -- Task 9

    SciTech Connect

    1996-08-01

    The Energy and Environmental Research Center (EERC) has teamed with SpinTek Membrane Systems, Inc., the developer of a centrifugal membrane filtration technology, to demonstrate applications for the SpinTek technology within the US Department of Energy (DOE) Environmental management (EM) Program. The technology uses supported microporous membranes rotating at high rpm, under pressure, to separate suspended and colloidal solids from liquid streams, yielding a solids-free permeate stream and a highly concentrated solids stream. This is a crosscutting technology that falls under the Efficient Separations and Processing Crosscutting Program, with potential application to tank wastes, contaminated groundwater, landfill leachate, and secondary liquid waste streams from other remediation processes, including decontamination and decommissioning systems. Membrane-screening tests were performed with the SpinTek STC-X4 static test cell filtration unit, using five ceramic membranes with different pore size and composition. Based on permeate flux, a 0.25-{micro}m TiO{sub 2}/Al{sub 2}O{sub 3} membrane was selected for detailed performance evaluation using the SpinTek ST-IIL centrifugal membrane filtration unit with a surrogate tank waste solution. An extended test run of 100 hr performed on a surrogate tank waste solution showed some deterioration in filtration performance, based on flux, apparently due to the buildup of solids near the inner portion of the membrane where relative membrane velocities were low. Continued testing of the system will focus on modifications to the shear pattern across the entire membrane surface to affect improved long-term performance.

  6. Fabric filtration for combustion sources

    SciTech Connect

    Donovan, R.P.

    1985-01-01

    Over the past decade, there has been an increase in the use of large-scale fabric filters. This book documents the improved understanding and technology that has accompanied that growth. It highlights laboratory and field experiences, covering the spectrum of fabric filtration activity. Reverse-air and pulse-jet cleaning technologies are described and equations for operating modes of fabric filters are provided.

  7. Hot gas filtration technical issues

    SciTech Connect

    Pontius, D.H.

    1995-11-01

    The primary objective of this research has been to provide an understanding of factors pertinent to the development of an effective filtration system for removing particles from high-temperature, high-pressure gas streams in advanced power generation systems under development by the Department of Energy. Information used to define the filtration system issues was compiled from the Morgantown Energy Technology Center (METC) Contractors Conferences, specific tasks assigned to Southern Research Institute, meetings with METC personnel and contractors, and other conferences and workshops organized by METC. Initial research and pilot scale installations have shown that there are some potential problem areas. Thick ash deposits have formed, bridging from passive surfaces to the filter material and between filter candles. A great number of ceramic filters have broken in various experimental and demonstration devices, especially during long-term testing. This paper reviews particulate characteristics (effects on filtration processes, conventional fly ash, gasifier char, PFBC ash, and detailed studies of PFBC ash) and ceramic filter materials (general issues, thermal stress, clay-bonded SiC filter materials, and monolithic ceramic materials).

  8. Assessments of factors that affect glomerular filtration rate and indirect markers of renal function in dogs and cats.

    PubMed

    Miyagawa, Yuichi; Takemura, Naoyuki; Hirose, Hisashi

    2010-09-01

    Chronic kidney disease is one of the most common disorders in dogs and cats. The plasma urea nitrogen (P-UN) and creatinine (P-Cre) concentrations are not sufficiently sensitive for early diagnosis of renal dysfunction. Although urine and plasma clearance methods allow earlier detection of reductions in the GFR, it is difficult to estimate a mildly reduced GFR from the values obtained by these methods, as they are also affected by physiological factors, such as body weight (BW) and age. The present study is a retrospective survey designed to assess the factors that affect markers of kidney function and to revaluate the clinical utility of the markers, including P-UN, P-Cre and GFR determined by plasma iohexol clearance (PCio) in dogs and cats. The P-UN, P-Cre and PCio values in dogs and the P-Cre and PCio values in cats were significantly correlated with BW (P<0.001). PCio in smaller dogs (≤ 15.0 kg) was significantly and inversely correlated with age. In smaller dogs, increase of P-UN alone might warrant a suspicion of a decreased GFR, but in contrast, P-Cre may be inefficient for detecting renal dysfunction or determining the severity of CKD compared with that in larger dogs (≥ 15.1 kg). P-Cre in larger dogs correlated better with PCio than in smaller dogs, suggesting that P-Cre in larger dogs was a more sensitive marker of reduced GFR. PMID:20410678

  9. Relationship between Estimated Glomerular Filtration Rate and Cardiovascular Mortality in a Japanese Cohort with Long-Term Follow-Up

    PubMed Central

    Nagai, Kei; Sairenchi, Toshimi; Irie, Fujiko; Watanabe, Hiroshi; Ota, Hitoshi; Yamagata, Kunihiro

    2016-01-01

    Background Patients with renal impairment are at risk of not only end-stage kidney disease but also cardiovascular disease (CVD). The current definition of CKD stage G3a is eGFR 45–59 ml/min/1.73 m2 and of G3b is 30–44 ml/min/1.73 m2, and subjects in the CKD 3a category are considered to be at lower risk of mortality than are those in CKD 3b. Methods We evaluated the outcome of 97,043 people (33,131 men and 63,912 women) living in Ibaraki Prefecture who underwent annual community-based health checkups beginning in 1993 at age 40–80 years and who were followed for a mean of 17.1 years. Results The number of all-causes deaths was 20,534 (10,375 men and 10,159 women), of which 5,995 (2,695 men and 3,300 women) were deaths due to CVD. Multivariable-adjusted hazard ratio for CVD death in the eGFR 45–49 ml/min/1.73 m2 category was significantly increased (1.82; 95% confidential interval, 1.23–2.69) in non-elderly men, whereas all-cause mortality and CVD mortality in elderly men with eGFR 45–49 ml/min/1.73m2 were non significant. In contrast, both in non-elderly women and in elderly women with eGFR 45–49 ml/min/1.73 m2 showed small, but significant, increases in the risks of all-cause mortality and CVD. Conclusions We demonstrated proportionate increases in mortality with decreasing eGFR in a Japanese CKD population. Like patients in the CKD G3b subgroup, non-elderly men and women with an eGFR of 45–49 ml/min/1.73 m2 (i.e. a part of CKD G3a) are at considerable risk of CVD mortality. Age dependent and eGFR dependent finer risk recognition were required for CVD prevention in clinical practice with regard to CKD patients. PMID:27272675

  10. Abnormal Head Position

    MedlinePlus

    ... cause. Can a longstanding head turn lead to any permanent problems? Yes, a significant abnormal head posture could cause permanent ... occipitocervical synostosis and unilateral hearing loss. Are there any ... postures? Yes. Abnormal head postures can usually be improved depending ...

  11. Urine - abnormal color

    MedlinePlus

    ... straw-yellow. Abnormally colored urine may be cloudy, dark, or blood-colored. Causes Abnormal urine color may ... red blood cells, or mucus in the urine. Dark brown but clear urine is a sign of ...

  12. Autoantibodies from mixed cryoglobulinaemia patients bind glomerular antigens.

    PubMed Central

    Dolcher, M P; Marchini, B; Sabbatini, A; Longombardo, G; Ferri, C; Riente, L; Bombardieri, S; Migliorini, P

    1994-01-01

    Mixed cryoglobulinaemia (MC) is a disorder characterized by the presence of large amounts of cryoprecipitating IgM-IgG complexes. An immune complex glomerulonephritis develops in one third of all patients, but its occurrence does not seem related to the amount of cryoglobulins in the sera, nor to their complement-fixing ability. In this study we investigated the presence of IgG antibodies reactive with kidney antigens in 33 MC patients (11 with glomerulonephritis, 22 without renal involvement). A total glomerular extract was run on a 10% acrylamide gel, blotted to nitrocellulose and probed with the patients' sera. Sera from half of the patients without renal involvement reacted with several glomerular antigens whose molecular weight ranged between 200 and 29 kD. In the group with renal involvement, sera from 7/11 patients reacted with an antigen of 50 kD, which is also expressed in thymus, but not in the heart or liver. In a follow-up study of four patients with renal involvement, the amount of serum antibody specific for the 50-kD antigen fluctuated, either spontaneously or in response to therapy. These results show that antibodies specific for glomerular antigens are detectable in MC sera. The immune response against a 50-kD antigen expressed in the kidney and thymus seems to be restricted to a subset of MC patients with renal involvement. Circulating autoantibodies specific for glomerular antigens might contribute to the induction of glomerulonephritis in MC forming immune complexes in situ. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 PMID:8187340

  13. Renal biopsy and pathologic evaluation of glomerular disease.

    PubMed

    Lees, George E; Cianciolo, Rachel E; Clubb, Fred J

    2011-08-01

    Presence of suspected primary glomerular disease is the most common and compelling reason to consider renal biopsy. Pathologic findings in samples from animals with nephritic or nephrotic glomerulopathies, as well as from animals with persistent subclinical glomerular proteinuria that is not associated with advanced chronic kidney disease, frequently guide treatment decisions and inform prognosis when suitable specimens are obtained and examined appropriately. Ultrasound-guided needle biopsy techniques generally are satisfactory; however, other methods of locating or approaching the kidney, such as manual palpation (e.g., in cats), laparoscopy, or open surgery, also can be used. Visual assessment of the tissue content of needle biopsy samples to verify that they are renal cortex (i.e., contain glomeruli) as they are obtained is a key step that minimizes the submission of uninformative samples for examination. Adequate planning for a renal biopsy also requires prior procurement of the fixatives and preservatives needed to process and submit samples that will be suitable for electron microscopic examination and immunostaining, as well as for light microscopic evaluation. Finally, to be optimally informative, renal biopsy specimens must be processed by laboratories that routinely perform the required specialized examinations and then be evaluated by experienced veterinary nephropathologists. The pathologic findings must be carefully integrated with one another and with information derived from the clinical investigation of the patient's illness to formulate the correct diagnosis and most informative guidance for therapeutic management of the animal's glomerular disease. PMID:21782145

  14. Involvement of glomerular SREBP-1c in diabetic nephropathy

    SciTech Connect

    Ishigaki, Naomi; Yamamoto, Takashi; Shimizu, Yoshio; Kobayashi, Kazuto; Yatoh, Shigeru; Sone, Hirohito; Takahashi, Akimitsu; Suzuki, Hiroaki; Yamagata, Kunihiro; Yamada, Nobuhiro; Shimano, Hitoshi

    2007-12-21

    The role of glomerular SREBP-1c in diabetic nephropathy was investigated. PEPCK-promoter transgenic mice overexpressing nuclear SREBP-1c exhibited enhancement of proteinuria with mesangial proliferation and matrix accumulation, mimicking diabetic nephropathy, despite the absence of hyperglycemia or hyperlipidemia. Isolated transgenic glomeruli had higher expression of TGF{beta}-1, fibronectin, and SPARC in the absence of marked lipid accumulation. Gene expression of P47phox, p67phox, and PU.1 were also activated, accompanying increased 8-OHdG in urine and kidney, demonstrating that glomerular SREBP-1c could directly cause oxidative stress through induced NADPH oxidase. Similar changes were observed in STZ-treated diabetic mice with activation of endogenous SREBP-1c. Finally, diabetic proteinuria and oxidative stress were ameliorated in SREBP-1-null mice. Adenoviral overexpression of active and dominant-negative SREBP-1c caused consistent reciprocal changes in expression of both profibrotic and oxidative stress genes in MES13 mesangial cells. These data suggest that activation of glomerular SREBP-1c could contribute to emergence and/or progression of diabetic nephropathy.

  15. Lymphohaemopoietic antigens of cultured human glomerular epithelial cells.

    PubMed Central

    van der Woude, F. J.; Michael, A. F.; Muller, E.; van der Hem, G. K.; Vernier, R. L.; Kim, Y.

    1989-01-01

    Glomerular visceral epithelial cells (GVEC) from normal human glomeruli were grown in tissue culture. Cell surface markers were studied by immunofluorescence microscopy using antibodies against lymphohaemopoietic differentiation antigens which are known to be present early (BA-1, OKB2, BA-2) and late (J5, anti CR1) in renal ontogenesis. Like foetal human glomerular epithelium, the cultured cells reacted with BA-1 and OKB2 (identifying an antigen expressed on B cells and polymorphonuclear leucocytes), and BA-2 (leukaemia-associated antigen), but were consistently negative for CR1 (C3b receptor); J5 which identifies the common acute lymphoblastic leukaemia antigen (CALLA) stained variably. Reactivity with antimyosin or anti factor VIII were absent. The cells produced an extracellular matrix containing laminin, type IV collagen, and fibronectin. This study supports the notion that GVEC undergo dedifferentiation as shown by the acquisition of lymphohaemopoietic differentiation antigens present early in renal ontogeny. In addition, the production of extracellular matrix constituents in vitro may be useful for the investigation of human glomerular basement membranes. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 PMID:2647119

  16. Water Filtration Using Plant Xylem

    PubMed Central

    Chambers, Valerie; Venkatesh, Varsha; Karnik, Rohit

    2014-01-01

    Effective point-of-use devices for providing safe drinking water are urgently needed to reduce the global burden of waterborne disease. Here we show that plant xylem from the sapwood of coniferous trees – a readily available, inexpensive, biodegradable, and disposable material – can remove bacteria from water by simple pressure-driven filtration. Approximately 3 cm3 of sapwood can filter water at the rate of several liters per day, sufficient to meet the clean drinking water needs of one person. The results demonstrate the potential of plant xylem to address the need for pathogen-free drinking water in developing countries and resource-limited settings. PMID:24587134

  17. Sioux City Riverbank Filtration Study

    NASA Astrophysics Data System (ADS)

    Mach, R.; Condon, J.; Johnson, J.

    2003-04-01

    The City of Sioux City (City) obtains a large percentage of their drinking water supply from both a horizontal collector well system and vertical wells located adjacent to the Missouri River. These wells are set in either the Missouri Alluvium or the Dakota Sandstone aquifer. Several of the collector well laterals extend out beneath the Missouri River, with the laterals being over twenty feet below the river channel bottom. Due to concerns regarding ground water under direct surface water influence, the Iowa Department of Natural Resources (IDNR) required the City to expand their water treatment process to deal with potential surface water contaminant issues. With the extensive cost of these plant upgrades, the City and Olsson Associates (OA) approached the IDNR requesting approval for assessing the degree of natural riverbank filtration for water treatment. If this natural process could be ascertained, the level of treatment from the plant could be reduced. The objective of this study was to quantify the degree of surface water (i.e. Missouri River) filtration due to the underlying Missouri River sediments. Several series of microscopic particulate analysis where conducted, along with tracking of turbidity, temperature, bacteria and a full scale particle count study. Six particle sizes from six sampling points were assessed over a nine-month period that spanned summer, fall and spring weather periods. The project was set up in two phases and utilized industry accepted statistical analyses to identify particle data trends. The first phase consisted of twice daily sample collection from the Missouri River and the collector well system for a one-month period. Statistical analysis of the data indicated reducing the sampling frequency and sampling locations would yield justifiable data while significantly reducing sampling and analysis costs. The IDNR approved this modification, and phase II included sampling and analysis under this reduced plant for an eight

  18. ANF inhibits vasopressin-induced Ca/sup 2 +/ mobilization and contraction in glomerular mesangial cells

    SciTech Connect

    Meyer-Lehnert, H.; Tsai, P.; Caramelo, C.; Schrier, R.W.

    1988-10-01

    It has been suggested that atrial natriuretic factor (ANF) may increase glomerular filtration rate (GFR) via alteration of the glomerular ultrafiltration area, which is at least in part regulated by the contractile state of mesangial cells. The present study therefore investigated the effect of ANF (atriopeptin III) on arginine vasopressin (AVP)-induced Ca2+ mobilization and contraction in cultured rat mesangial cells. AVP (10(-8) M) increased intracellular Ca2+ (( Ca2+)i) as measured by the quin2 method (142.1 +/- 3.7 vs. 297.9 +/- 8.9 nM, P less than 0.001). This effect, however, was diminished by 10(-8) M ANF (297.9 +/- 8.9 vs. 233.1 +/- 9.3 nM, P less than 0.0025). ANF alone did not affect basal (Ca2+)i. AVP-stimulated 45Ca2+ efflux (cpm.mg prot-1.30 s-1) from mesangial cells within 30 s (1,432 +/- 70 basal vs. 2,751 +/- 287 AVP at 30 s, P less than 0.001). This effect of AVP on 45Ca2+ efflux was also inhibited by ANF (1,403 +/- 62 basal vs. 1,584 +/- 87 AVP and ANF, NS); ANF alone had no effect on spontaneous 45Ca2+ efflux. Furthermore, ANF inhibited AVP-induced 45Ca2+ uptake, which is purportedly one of the major determinants of the sustained phase of cell contraction. Cell contraction was assessed by digital imaging analysis. AVP (10(-7) M) caused contraction of 33.8 +/- 2.0% of the cells, but the contractile response decreased to 20.7 +/- 2.3% in the presence of 10(-9) M ANF and was virtually abolished in the presence of 10(-8) M ANF. Guanosine 3',5'-cyclic monophosphate (cGMP) has been proposed as the second messenger for ANF. ANF (10(-7) M) stimulated cGMP production significantly (0.54 +/- 0.12 vs. 22.30 +/- 5.91 pmol.mg prot-1.10 min-1, P less than 0.01), but it had no effect on cGMP at concentrations of 10(-8) M and below. 8-Bromo-cGMP (8-BrcGMP) attenuated the stimulatory effect of AVP on (Ca2+)i, 45Ca2+ efflux, and 45Ca2+ uptake.

  19. Pig manure treatment and purification by filtration.

    PubMed

    Makara, A; Kowalski, Z

    2015-09-15

    This study aimed to develop a new, complex pig manure treatment and filtration process. The final scheme, called the AMAK process, comprised the following successive steps: mineralization with mineral acids, alkalization with lime milk, superphosphate addition, a second alkalization, thermal treatment, and pressure filtration. The proposed method produced a filtrate with 95%, 80%, and 96% reductions in chemical oxygen demand, nitrogen content, and phosphorus content, respectively. An advantage of the proposed method was that it incorporated a crystalline phase into the solid organic part of the manure, which enabled high filtration rates (>1000 kg m(-2) h(-1)) and efficient separation. The process also eliminated odor emissions from the filtrate and sediment. The treated filtrate could be used to irrigate crops or it could be further treated in conventional biological wastewater treatment plants. The sediment could be used for producing mineral-organic fertilizer. The AMAK process is inexpensive, and it requires low investment costs. PMID:26197426

  20. Membrane filtration of food suspensions.

    PubMed Central

    Sharpe, A N; Peterkin, P I; Dudas, I

    1979-01-01

    Factors affecting the membrane filtration of food suspensions were studied for 58 foods and 13 membrane filters. Lot number within a brand, pore size (0.45 or 0.8 micrometer), and time elapsed before filtration had little effect on filterability. Brand of membrane filter, flow direction, pressure differential, age (microbiological quality) of the food, duration of the blending process, temperature, and concentration of food in the suspension had significant and often predictable effects. Preparation of suspensions by Stomacher (relative to rotary blender) addition of surfactant (particularly at elevated temperature) and prior incubation with proteases sometimes had dramatic effects of filterability. In contrast to popular opinion, foods can be membrane filtered in quantities pertinent to the maximums used in conventional plating procedures. Removal of growth inhibitors and food debris is possible by using membrane filters. Lowering of the limits of detection of microorganisms by concentration on membrane filters can be considered feasible for many foods. The data are particularly relevant to the use of hydrophobic grid-membrane filters (which are capable of enumerating up to 9 X 10(4) organisms per filter) in instrumented methods of food microbiological analysis. Images PMID:760637

  1. Nonwoven filtration mat production by electrospinning method

    NASA Astrophysics Data System (ADS)

    Lackowski, M.; Krupa, A.; Jaworek, A.

    2011-06-01

    The filtration of nanoparticles and submicron particles is an important problem in industry and health protection. One of the methods which can be used to solve this problem is to use nonwoven nanofibrous filters. The process of producing filtration mats of different thickness by electrospinning is presented in the paper. The experimental results on filtration properties of nanofibrous filter mat, including the efficiency of removal of cigarette smoke particles from a gas are also presented.

  2. Side Stream Filtration for Cooling Towers

    SciTech Connect

    2012-10-20

    This technology evaluation assesses side stream filtration options for cooling towers, with an objective to assess key attributes that optimize energy and water savings along with providing information on specific technology and implementation options. This information can be used to assist Federal sites to determine which options may be most appropriate for their applications. This evaluation provides an overview of the characterization of side stream filtration technology, describes typical applications, and details specific types of filtration technology.

  3. Injury to the Endothelial Surface Layer Induces Glomerular Hyperfiltration Rats with Early-Stage Diabetes

    PubMed Central

    Zhang, Chunyang; Meng, Yao; Liu, Qi; Xuan, Miao; Zhang, Lanyu; Deng, Bo; Zhang, Keqin; Liu, Zhimin; Lei, Tao

    2014-01-01

    Glomerular endothelial surface layer (ESL) may play a role in the mechanisms of albuminuria in diabetic nephropathy, which lack evidence in vivo. The effects of high glucose on the passage of albumin across the glomerular ESL were analysed in streptozotocin-induced diabetic Sprague-Dawley rats for 4 weeks. Albuminuria and glomerular mesangial matrix were significantly increased in diabetic rats. The passage of albumin across the ESL, as measured by albumin-colloid gold particle density in the glomerular basement membrane (GBM), was increased significantly in diabetic rats. The thickness of the glomerular ESL, examined indirectly by infusing Intralipid into vessels using an electron microscope, was significantly decreased and the GBM exhibited little change in diabetic rats. In summary, the glomerular ESL may play a role in the pathogenesis of albuminuria in rats with early-stage diabetes. PMID:24812636

  4. Matrix metalloproteinase 12 modulates high-fat-diet induced glomerular fibrogenesis and inflammation in a mouse model of obesity

    PubMed Central

    Niu, Honglin; Li, Ying; Li, Haibin; Chi, Yanqing; Zhuang, Minghui; Zhang, Tao; Liu, Maodong; Nie, Lei

    2016-01-01

    Obesity-induced kidney injury contributes to albuminuria, which is characterized by a progressive decline in renal function leading to glomerulosclerosis and renal fibrosis. Matrix metalloproteinases (MMPs) modulate inflammation and fibrosis by degrading a variety of extracellular matrix and regulating the activities of effector proteins. Abnormal regulation of MMP-12 expression has been implicated in abdominal aortic aneurysm, atherosclerosis, and emphysema, but the underlying mechanisms remain unclear. The present study examined the function of MMP-12 in glomerular fibrogenesis and inflammation using apo E−/− or apo E−/−MMP-12−/− mice and maintained on a high-fat-diet (HFD) for 3, 6, or 9 months. MMP-12 deletion reduced glomerular matrix accumulation, and downregulated the expression of NADPH oxidase 4 and the subunit-p67phox, indicating the inhibition of renal oxidative stress. In addition, the expression of the inflammation-associated molecule MCP-1 and macrophage marker-CD11b was decreased in glomeruli of apo E−/−MMP-12−/− mice fed HFD. MMP-12 produced by macrophages infiltrating into glomeruli contributed to the degradation of collagen type IV and fibronectin. Crescent formation due to renal oxidative stress in Bowman’s space was a major factor in the development of fibrogenesis and inflammation. These results suggest that regulating MMP-12 activity could be a therapeutic strategy for the treatment of crescentic glomerulonephritis and fibrogenesis. PMID:26822129

  5. COMPARISON OF SOME FILTRATION PROCESSES APPROPRIATE FOR GIARDIA CYST REMOVAL

    EPA Science Inventory

    Slow sand filtration, diatomaceous earth (DE) filtration, and coagulation-filtration (including conventional treatment, direct filtration, and in-line filtration), have been evaluated for Giardia cyst removal at pilot plant and/or field scale. Properly designed and operated, the ...

  6. RIVERBANK FILTRATION EFFECTIVENESS IN AN ARID ENVIRONMENT

    EPA Science Inventory

    This experiment is a field test of bank filtration at a site where water level and salinity vary on an annual basis, as they do in many arid and semi-arid streams. No other studies of bank filtration have been performed in this kind of setting. Along the border with Mexico, shall...

  7. 40 CFR 141.73 - Filtration.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS (CONTINUED) NATIONAL PRIMARY DRINKING WATER REGULATIONS Filtration and Disinfection § 141.73 Filtration. A public water system that uses a surface water source or a ground water source under the direct influence of surface...

  8. 40 CFR 141.173 - Filtration.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS (CONTINUED) NATIONAL PRIMARY DRINKING WATER REGULATIONS Enhanced Filtration and Disinfection-Systems Serving 10,000 or More People § 141.173 Filtration. A public water system subject to the requirements of this subpart that...

  9. Statin-sensitive endocytosis of albumin by glomerular podocytes.

    PubMed

    Eyre, Jeanette; Ioannou, Kyriakos; Grubb, Blair D; Saleem, Moin A; Mathieson, Peter W; Brunskill, Nigel J; Christensen, Erik I; Topham, Peter S

    2007-02-01

    Glomerular podocytes are critical regulators of glomerular permeability via the slit diaphragm and may play a role in cleaning the glomerular filter. Whether podocytes are able to endocytose proteins is uncertain. We studied protein endocytosis in conditionally immortalized mouse and human podocytes using FITC-albumin by direct quantitative assay and by fluorescence microscopy and electron microscopy in mouse podocytes. Furthermore, in vivo uptake was studied in human, rat, and mouse podocytes. Both mouse and human podocytes displayed specific one-site binding for FITC-albumin with K(d) of 0.91 or 0.44 mg/ml and B(max) of 3.15 or 0.81 microg/mg cell protein, respectively. In addition, they showed avid endocytosis of FITC-albumin with K(m) of 9.48 or 4.5 mg/ml and V(max) of 474.3 or 97.4 microg.mg cell protein(-1).h(-1), respectively. Immunoglobulin and transferrin were inefficient competitors of this process, indicating some specificity for albumin. Accumulation of endocytosed albumin could be demonstrated in intracellular vesicles by fluorescence confocal microscopy and electron microscopy. Endocytosis was sensitive to pretreatment with simvastatin. In vivo accumulation of albumin was found in all three species but was most pronounced in the rat. We conclude that podocytes are able to endocytose protein in a statin-sensitive manner. This function is likely to be highly significant in health and disease. In addition, protein endocytosis by podocytes may represent a useful, measurable phenotypic characteristic against which potentially injurious or beneficial interventions can be assessed. PMID:17032937

  10. Tensin2-deficient mice on FVB/N background develop severe glomerular disease

    PubMed Central

    UCHIO-YAMADA, Kozue; MONOBE, Yoko; AKAGI, Ken-ichi; YAMAMOTO, Yoshie; OGURA, Atsuo; MANABE, Noboru

    2016-01-01

    Tensin2 (Tns2) is an essential component for the maintenance of glomerular basement membrane (GBM) structures. Tns2-deficient mice were previously shown to develop mild glomerular injury on a DBA/2 background, but not on a C57BL/6J or a 129/SvJ background, suggesting that glomerular injury by the deletion of Tns2 was strongly dependent on the genetic background. To further understand the mechanisms for the onset and the progression of glomerular injury by the deletion of Tns2, we generated Tns2-deficient mice on an FVB/N (FVB) strain, which is highly sensitive to glomerular disease. Tns2-deficient mice on FVB (FVBGN) developed severe nephrotic syndrome, and female FVBGN mice died within 8 weeks. Ultrastructural analysis revealed that FVBGN mice exhibited severe glomerular defects with mesangial process invasion of glomerular capillary tufts, lamination and thickening of the GBM and subsequent podocyte foot process effacement soon after birth. Aberrant laminin components containing α1, α2 and β1 chains, which are normally expressed in the mesangium, accumulated in the GBM of FVBGN, suggesting that these components originated from mesangial cells that invaded glomerular capillary tufts. Compared to Tns2-deficient mice on the other backgrounds in previous reports, FVBGN mice developed earlier onset of glomerular defects and rapid progression of renal failure. Thus, this study further extended our understanding of the possible genetic background effect on the deterioration of nephrotic syndrome by Tns2 deficiency. PMID:26854109

  11. Tensin2-deficient mice on FVB/N background develop severe glomerular disease.

    PubMed

    Uchio-Yamada, Kozue; Monobe, Yoko; Akagi, Ken-Ichi; Yamamoto, Yoshie; Ogura, Atsuo; Manabe, Noboru

    2016-06-01

    Tensin2 (Tns2) is an essential component for the maintenance of glomerular basement membrane (GBM) structures. Tns2-deficient mice were previously shown to develop mild glomerular injury on a DBA/2 background, but not on a C57BL/6J or a 129/SvJ background, suggesting that glomerular injury by the deletion of Tns2 was strongly dependent on the genetic background. To further understand the mechanisms for the onset and the progression of glomerular injury by the deletion of Tns2, we generated Tns2-deficient mice on an FVB/N (FVB) strain, which is highly sensitive to glomerular disease. Tns2-deficient mice on FVB (FVBGN) developed severe nephrotic syndrome, and female FVBGN mice died within 8 weeks. Ultrastructural analysis revealed that FVBGN mice exhibited severe glomerular defects with mesangial process invasion of glomerular capillary tufts, lamination and thickening of the GBM and subsequent podocyte foot process effacement soon after birth. Aberrant laminin components containing α1, α2 and β1 chains, which are normally expressed in the mesangium, accumulated in the GBM of FVBGN, suggesting that these components originated from mesangial cells that invaded glomerular capillary tufts. Compared to Tns2-deficient mice on the other backgrounds in previous reports, FVBGN mice developed earlier onset of glomerular defects and rapid progression of renal failure. Thus, this study further extended our understanding of the possible genetic background effect on the deterioration of nephrotic syndrome by Tns2 deficiency. PMID:26854109

  12. Use of Cationized Ferritin Nanoparticles to Measure Renal Glomerular Microstructure with MRI.

    PubMed

    Bennett, Kevin M; Beeman, Scott C; Baldelomar, Edwin J; Zhang, Min; Wu, Teresa; Hann, Bradley D; Bertram, John F; Charlton, Jennifer R

    2016-01-01

    Magnetic resonance imaging (MRI) is becoming important for whole-kidney assessment of glomerular morphology, both in vivo and ex vivo. MRI-based renal morphological measurements can be made in intact organs and allow direct measurements of every perfused glomerulus. Cationic ferritin (CF) is used as a superparamagnetic contrast agent for MRI. CF binds to the glomerular basement membrane after intravenous injection, allowing direct, whole-kidney measurements of glomerular number, volume, and volume distribution. Here we describe the production, testing, and use of CF as an MRI contrast agent for quantitative glomerular morphology in intact mouse, rat, and human kidneys. PMID:26676128

  13. Protein- and diabetes-induced glomerular hyperfiltration: role of glucagon, vasopressin, and urea.

    PubMed

    Bankir, Lise; Roussel, Ronan; Bouby, Nadine

    2015-07-01

    A single protein-rich meal (or an infusion of amino acids) is known to increase the glomerular filtration rate (GFR) for a few hours, a phenomenon known as "hyperfiltration." It is important to understand the factors that initiate this upregulation because it becomes maladaptive in the long term. Several mediators and paracrine factors have been shown to participate in this upregulation, but they are not directly triggered by protein intake. Here, we explain how a rise in glucagon and in vasopressin secretion, directly induced by protein ingestion, might be the initial factors triggering the hepatic and renal events leading to an increase in the GFR. Their effects include metabolic actions in the liver and stimulation of sodium chloride reabsorption in the thick ascending limb. Glucagon is not only a glucoregulatory hormone. It is also important for the excretion of nitrogen end products by stimulating both urea synthesis in the liver (along with gluconeogenesis from amino acids) and urea excretion by the kidney. Vasopressin allows the concentration of nitrogenous end products (urea, ammonia, etc.) and other protein-associated wastes in a hyperosmotic urine, thus allowing a very significant water economy characteristic of all terrestrial mammals. No hyperfiltration occurs in the absence of one or the other hormone. Experimental results suggest that the combined actions of these two hormones, along with the complex intrarenal handling of urea, lead to alter the composition of the tubular fluid at the macula densa and to reduce the intensity of the signal activating the tubuloglomerular feedback control of GFR, thus allowing GFR to raise. Altogether, glucagon, vasopressin, and urea contribute to set up the best compromise between efficient urea excretion and water economy. PMID:25925260

  14. Tooth - abnormal shape

    MedlinePlus

    Hutchinson incisors; Abnormal tooth shape; Peg teeth; Mulberry teeth; Conical teeth ... The appearance of normal teeth varies, especially the molars. ... conditions. Specific diseases can affect tooth shape, tooth ...

  15. Tooth - abnormal shape

    MedlinePlus

    Hutchinson incisors; Abnormal tooth shape; Peg teeth; Mulberry teeth; Conical teeth ... from many different conditions. Specific diseases can affect tooth shape, tooth color, time of appearance, or absence ...

  16. Hypertension, glomerular hypertrophy and nephrosclerosis: the effect of race

    PubMed Central

    Hughson, Michael D.; Puelles, Victor G.; Hoy, Wendy E.; Douglas-Denton, Rebecca N.; Mott, Susan A.; Bertram, John F.

    2014-01-01

    Background African Americans have more severe hypertensive nephrosclerosis than white Americans, possibly at similar levels of blood pressure. Glomerular volume is increased in African Americans relative to whites, but it is uncertain how this relates to nephrosclerosis and whether it contributes to or compensates for glomerulosclerosis. Methods Stereological disector/fractionator estimates of glomerular number (Nglom) and average glomerular volume (Vglom) were obtained on autopsy kidneys of 171 African Americans and 131 whites. Eighty-eight African Americans and 49 whites were identified as hypertensive. Nephrosclerosis was measured morphometrically as the percentage of glomerulosclerosis, proportion of cortical fibrosis and interlobular artery intimal thickness, and analyzed with Vglom by age, race, gender, body mass index (BMI) and blood pressure. Results African Americans were more frequently hypertensive (58.5%) than whites (35.8%) and when hypertensive had higher levels of blood pressure (P = 0.02). Nglom was significantly lower in hypertensive compared with non-hypertensive subjects among white women (P = 0.02) but not white males (P = 0.34) or African American females (P = 0.10) or males (P = 0.41). For each race and gender, glomerulosclerosis, cortical fibrosis and arterial intimal thickening were statistically correlated with age (P < 0.001) and hypertension (P < 0.001) and increased Vglom with hypertension (P < 0.001) and BMI (P < 0.001). In multivariate analysis, African American race was associated with increased Vglom (P = 0.01) and arterial intimal thickening (P < 0.01), while interactions between race and blood pressure indicated that the severity of nephrosclerosis including increased Vglom was linked most directly to hypertension without significant contributions from race. The hypertension-associated enlargement of Vglom was present with mild degrees of glomerulosclerosis and changed little as the severity of glomerulosclerosis increased

  17. A neural network model for olfactory glomerular activity prediction

    NASA Astrophysics Data System (ADS)

    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.

  18. Drug-Induced Glomerular Disease: Immune-Mediated Injury

    PubMed Central

    Markowitz, Glen S.; Radhakrishnan, Jai

    2015-01-01

    Drug-induced autoimmune disease was initially described decades ago, with reports of vasculitis and a lupus-like syndrome in patients taking hydralazine, procainamide, and sulfadiazine. Over the years, multiple other agents have been linked to immune-mediated glomerular disease, often with associated autoantibody formation. Certain clinical and laboratory features may distinguish these entities from their idiopathic counterparts, and making this distinction is important in the diagnosis and management of these patients. Here, drug-induced, ANCA-associated vasculitis, drug-induced lupus, and drug-associated membranous nephropathy are reviewed. PMID:26092827

  19. [Tubular involvement in glomerular diseases of the kidney (author's transl)].

    PubMed

    Lubee, G; Balzar, E

    1977-01-21

    An attempt is made in this study to provide an answer to the question whether glomerular diseases are accompanied by tubular disorders. The urinary lysozyme activity was determined by means of a turbidimetric assay method in 10 healthy children as controls, 10 patients with glomerulonephritis, 8 patients with Alport's syndrome (hereditary glomerulonephritis with deafness) and 12 children with idiopathic nephrotic syndrome. In most of the cases a significant increase in urinary lysozyme excretion, indicative of tubular damage, was found and this finding correlates well with the tubular morphology of the patients. PMID:320767

  20. Laminin and Type IV Collagen Isoform Substitutions Occur in Temporally and Spatially Distinct Patterns in Developing Kidney Glomerular Basement Membranes

    PubMed Central

    St. John, Patricia L.; Stroganova, Larysa; Zelenchuk, Adrian; Steenhard, Brooke M.

    2013-01-01

    Kidney glomerular basement membranes (GBMs) undergo laminin and type IV collagen isoform substitutions during glomerular development, which are believed to be required for maturation of the filtration barrier. Specifically, GBMs of earliest glomeruli contain laminin α1β1γ1 and collagen α1α2α1(IV), whereas mature glomeruli contain laminin α5β2γ1 and collagen α3α4α5(IV). Here, we used confocal microscopy to simultaneously evaluate expression of different laminin and collagen IV isoforms in newborn mouse GBMs. Our results show loss of laminin α1 from GBMs in early capillary loop stages and continuous linear deposition of laminin bearing the α5 chain thereafter. In contrast, collagen α1α2α1(IV) persisted in linear patterns into late capillary loop stages, when collagen α3α4α5(IV) first appeared in discontinuous, non-linear patterns. This patchy pattern for collagen α3α4α5(IV) continued into maturing glomeruli where there were lengths of linear, laminin α5-positive GBM entirely lacking either isoform of collagen IV. Relative abundance of laminin and collagen IV mRNAs in newborn and 5-week-old mouse kidneys also differed, with those encoding laminin α1, α5, β1, β2, and γ1, and collagen α1(IV) and α2(IV) chains all significantly declining at 5 weeks, but α3(IV) and α4(IV) were significantly upregulated. We conclude that different biosynthetic mechanisms control laminin and type IV collagen expression in developing glomeruli. PMID:23896970

  1. 11. View of east entry to central corridor of filtration ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    11. View of east entry to central corridor of filtration bed building. - Lake Whitney Water Filtration Plant, Filtration Plant, South side of Armory Street between Edgehill Road & Whitney Avenue, Hamden, New Haven County, CT

  2. 12. View west of access bridge to top of filtration ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    12. View west of access bridge to top of filtration bed building. - Lake Whitney Water Filtration Plant, Filtration Plant, South side of Armory Street between Edgehill Road & Whitney Avenue, Hamden, New Haven County, CT

  3. 14. View of damage to southeast corner of filtration building. ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    14. View of damage to southeast corner of filtration building. Note construction of concrete over brick. - Lake Whitney Water Filtration Plant, Filtration Plant, South side of Armory Street between Edgehill Road & Whitney Avenue, Hamden, New Haven County, CT

  4. 10. OBLIQUE DETAIL VIEW OF PUMP NO. 1 IN FILTRATION ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    10. OBLIQUE DETAIL VIEW OF PUMP NO. 1 IN FILTRATION ROOM IN FILTRATION PLANT (#1773), LOOKING NORTHEAST - Presidio Water Treatment Plant, Filtration Plant, East of Lobos Creek at Baker Beach, San Francisco, San Francisco County, CA

  5. 32. Piping under central corridor of filtration bed building. ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    32. Piping under central corridor of filtration bed building. - Lake Whitney Water Filtration Plant, Filtration Plant, South side of Armory Street between Edgehill Road & Whitney Avenue, Hamden, New Haven County, CT

  6. 8. Detail view of southwest corner of filtration bed building. ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    8. Detail view of southwest corner of filtration bed building. - Lake Whitney Water Filtration Plant, Filtration Plant, South side of Armory Street between Edgehill Road & Whitney Avenue, Hamden, New Haven County, CT

  7. 13. View of west entrance to central corridor of filtration ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    13. View of west entrance to central corridor of filtration bed building. - Lake Whitney Water Filtration Plant, Filtration Plant, South side of Armory Street between Edgehill Road & Whitney Avenue, Hamden, New Haven County, CT

  8. 7. View east of southeast corner of filtration bed building. ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    7. View east of southeast corner of filtration bed building. Laboratory building is at center left of photograph. - Lake Whitney Water Filtration Plant, Filtration Plant, South side of Armory Street between Edgehill Road & Whitney Avenue, Hamden, New Haven County, CT

  9. 1. Perspective view southwest of filtration bed with earth mounded ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    1. Perspective view southwest of filtration bed with earth mounded over facility. Armory Street appears in the foreground. - Lake Whitney Water Filtration Plant, Filtration Plant, South side of Armory Street between Edgehill Road & Whitney Avenue, Hamden, New Haven County, CT

  10. 4. View south of rear of filtration bed building. ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    4. View south of rear of filtration bed building. - Lake Whitney Water Filtration Plant, Filtration Plant, South side of Armory Street between Edgehill Road & Whitney Avenue, Hamden, New Haven County, CT

  11. 31. Piping under central corridor of filtration bed building. ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    31. Piping under central corridor of filtration bed building. - Lake Whitney Water Filtration Plant, Filtration Plant, South side of Armory Street between Edgehill Road & Whitney Avenue, Hamden, New Haven County, CT

  12. Structurally abnormal human autosomes

    SciTech Connect

    1993-12-31

    Chapter 25, discusses structurally abnormal human autosomes. This discussion includes: structurally abnormal chromosomes, chromosomal polymorphisms, pericentric inversions, paracentric inversions, deletions or partial monosomies, cri du chat (cat cry) syndrome, ring chromosomes, insertions, duplication or pure partial trisomy and mosaicism. 71 refs., 8 figs.

  13. Nanoscale protein architecture of the kidney glomerular basement membrane

    PubMed Central

    Suleiman, Hani; Zhang, Lei; Roth, Robyn; Heuser, John E; Miner, Jeffrey H; Shaw, Andrey S; Dani, Adish

    2013-01-01

    In multicellular organisms, proteins of the extracellular matrix (ECM) play structural and functional roles in essentially all organs, so understanding ECM protein organization in health and disease remains an important goal. Here, we used sub-diffraction resolution stochastic optical reconstruction microscopy (STORM) to resolve the in situ molecular organization of proteins within the kidney glomerular basement membrane (GBM), an essential mediator of glomerular ultrafiltration. Using multichannel STORM and STORM-electron microscopy correlation, we constructed a molecular reference frame that revealed a laminar organization of ECM proteins within the GBM. Separate analyses of domains near the N- and C-termini of agrin, laminin, and collagen IV in mouse and human GBM revealed a highly oriented macromolecular organization. Our analysis also revealed disruptions in this GBM architecture in a mouse model of Alport syndrome. These results provide the first nanoscopic glimpse into the organization of a complex ECM. DOI: http://dx.doi.org/10.7554/eLife.01149.001 PMID:24137544

  14. A Compendium of Urinary Biomarkers Indicative of Glomerular Podocytopathy

    PubMed Central

    2013-01-01

    It is well known that glomerular podocyte injury and loss are present in numerous nephropathies and that the pathophysiologic consecution of disease hinges upon the fate of the podocyte. While multiple factors play a hand in glomerulopathy progression, basic logic lends that if one monitors the podocyte's status, that may reflect the status of disease. Recent investigations have focused on what one can elucidate from the noninvasive collection of urine, and have proven that certain, specific biomarkers of podocytes can be readily identified via varying techniques. This paper has brought together all described urinary biomarkers of podocyte injury and is made to provide a concise summary of their utility and testing in laboratory and clinical theatres. While promising in the potential that they hold as tools for clinicians and investigators, the described biomarkers require further comprehensive vetting in the form of larger clinical trials and studies that would give their value true weight. These urinary biomarkers are put forth as novel indicators of glomerular disease presence, disease progression, and therapeutic efficacy that in some cases may be more advantageous than the established parameters/measures currently used in practice. PMID:24327929

  15. Glomerular interactions in olfactory processing channels of the antennal lobes

    PubMed Central

    Heinbockel, Thomas; Shields, Vonnie D. C.; Reisenman, Carolina E.

    2014-01-01

    An open question in olfactory coding is the extent of interglomerular connectivity: do olfactory glomeruli and their neurons regulate the odorant responses of neurons innervating other glomeruli? In the olfactory system of the moth Manduca sexta, the response properties of different types of antennal olfactory receptor cells are known. Likewise, a subset of antennal lobe glomeruli has been functionally characterized and the olfactory tuning of their innervating neurons identified. This provides a unique opportunity to determine functional interactions between glomeruli of known input, specifically, (1) glomeruli processing plant odors and (2) glomeruli activated by antennal stimulation with pheromone components of conspecific females. Several studies describe reciprocal inhibitory effects between different types of pheromone-responsive projection neurons suggesting lateral inhibitory interactions between pheromone component-selective glomerular neural circuits. Furthermore, antennal lobe projection neurons that respond to host plant volatiles and innervate single, ordinary glomeruli are inhibited during antennal stimulation with the female’s sex pheromone. The studies demonstrate the existence of lateral inhibitory effects in response to behaviorally significant odorant stimuli and irrespective of glomerular location in the antennal lobe. Inhibitory interactions are present within and between olfactory subsystems (pheromonal and non-pheromonal subsystems), potentially to enhance contrast and strengthen odorant discrimination. PMID:23893248

  16. A Case Report of Adrenocorticotropic Hormone to Treat Recurrent Focal Segmental Glomerular Sclerosis Post-Transplantation and Biomarker Monitoring

    PubMed Central

    Anwar, Siddiq; Larson, Derek S.; Naimi, Nima; Ashraf, Muhammad; Culiberk, Nancy; Liapis, Helen; Wei, Changli; Reiser, Jochen; Brennan, Daniel C.

    2015-01-01

    Background: Recurrent focal segmental glomerular sclerosis (rFSGS) in renal transplant recipients (RTR) is difficult to predict and treat. Early rFSGS is likely from circulating factors and preformed antibodies. Methods: We present the case of a 23-year-old white man who presented with rFSGS and acute renal failure, requiring dialysis 9-months after a 1-haplotype matched living-related transplant. We retrospectively analyzed serum samples from various clinical stages for rFSGS biomarkers: serum glomerular albumin permeability (Palb), soluble urokinase-type plasminogen activator receptor (suPAR) serum level with suPAR-β3 integrin signaling on human podocytes, and angiotensin II type I receptor-antibody (AT1R-Ab) titer. Results: All biomarkers were abnormal at 1-year pre-transplant prior to initiation of dialysis and at the time of transplant. After initiation of hemodialysis, β3 integrin activity on human podocytes, in response to patient serum, as well as AT1R-Ab were further elevated. At the time of biopsy-proven recurrence, all biomarkers were abnormally high. One week after therapy with aborted plasmapheresis (secondary to intolerance), and high dose steroids, the Palb and suPAR-β3 integrin activity remained significantly positive. After 12-weeks of treatment with high-dose steroids, rituximab, and galactose, the patient remained hemodialysis-dependent. Three-months after his initial presentation, we commenced adrenocorticotropic hormone (ACTH, Acthar® Gel), 80 units subcutaneously twice weekly. Four-weeks later, he was able to discontinue dialysis. After 8-months of maintenance ACTH therapy, his serum creatinine stabilized at 1.79 mg/dL with <1 g of proteinuria. Conclusion: ACTH therapy was associated with improvement in renal function within 4 weeks. The use of rFSGS biomarkers may aid in predicting development of rFSGS. PMID:25853133

  17. Mesangial cell, glomerular and renal vascular responses to endothelin in the rat kidney. Elucidation of signal transduction pathways.

    PubMed Central

    Badr, K F; Murray, J J; Breyer, M D; Takahashi, K; Inagami, T; Harris, R C

    1989-01-01

    We investigated the actions of endothelin in anesthetized rats and cultured mesangial cells. Intravenous infusion of endothelin (10 pmol/min) decreased renal blood flow by 44% at 20 min without changing arterial pressure, which subsequently rose significantly from 124 +/- 3 to 133 +/- 4 mmHg over 60 min. Micropuncture during the nonhypertensive period revealed increases in afferent (65%) and efferent (82%) arteriolar resistances, thereby reducing nephron plasma flow rate. The glomerular ultrafiltration coefficient (Kf) fell from 0.097 +/- 0.035 to 0.031 +/- 0.011 nl/(s.mmHg) as did single nephron filtration rate (41 +/- 3 to 19 +/- 3 nl/min). Addition of 5 nM endothelin to mesangial cells plated on a silicone rubber substrate increased the intensity and number of tension-generated wrinkles, and caused their reappearance in forskolin prerelaxed cells. 20-30 s following exposure of fura-2 loaded mesangial cells to 10 nM endothelin, single cell intracellular calcium concentration ([Ca]i) increased from a mean baseline value of 66 +/- 11 (SE) to a peak of 684 +/- 250 nM (P less than 0.05) followed by a sustained elevation at 145 +/- 42 nM. Anion exchange HPLC revealed rapid (15 s) and dose-dependent stimulation of inositol 1,4,5-trisphosphate (IP3) generation following exposure of [3H]myoinositol preloaded mesangial cells to 10-100 nM endothelin. Endothelin also led to intracellular alkalinization of 2'7'-bis(2-carboxy-ethyl)-5(and-6)carboxyfluorescein (BCECF)-loaded mesangial cells and its addition was associated with dramatic augmentation of mitogenic activity. Thus, endothelin exerts potent constrictor effects on renal arterioles which precede its systemic hypertensive action. It lowers Kf and contracts mesangial cells, likely through stimulation of IP3 generation and elevation of [Ca]i. It is a potent mesangial cell mitogen. These studies define functional responses and signal transduction pathways for endothelin in the rat kidney and propose a potential role for

  18. High-temperature gas filtration

    SciTech Connect

    Schiffer, H.P.; Laux, S.; Renz, U. . Lehrstuhl fuer Waermeuebertragung und Klimatechnik)

    1992-10-01

    High-temperature, high-pressure filtration is important to the development of fluidized-bed combustion (FBC) technology. This volume describes the commissioning and testing of a pilot-scale filter module rated at 1 to 4 bar pressure and up to 900[degrees]C. The module consists of an array of six porous sintered silicon carbide filter elements, designed to be cleaned on-line by jet pulses of compressed air. More than 2000 hours of exposure were achieved with FBC combustion gas with inlet dust concentrations of 500 to 40,000 ppM[sub w] at 200 to 650[degrees]C. Another 3500 hours of operation were achieved with simulated gas and injected dust. The filter elements were subjected to 60,000 cleaning cycles. No dust penetration through the filter modules was detected. After an initial stabilizing period, pressure drop remained moderate at less that 50 mbar (0.7 psi). The energy expended in pulse cleaning was negligible. No crusty deposits of dust were found on the filter elements during inspections, and no irreversible blinding occurred.

  19. Filtrating forms of soil bacteria

    NASA Astrophysics Data System (ADS)

    Van'kova, A. A.; Ivanov, P. I.; Emtsev, V. T.

    2013-03-01

    Filtrating (ultramicroscopic) forms (FF) of bacteria were studied in a soddy-podzolic soil and the root zone of alfalfa plants as part of populations of the most widespread physiological groups of soil bacteria. FF were obtained by filtering soil solutions through membrane filters with a pore diameter of 0.22 μm. It was established that the greater part of the bacteria in the soil and in the root zone of the plants has an ultramicroscopic size: the average diameter of the cells is 0.3 μm, and their length is 0.6 μm, which is significantly less than the cell size of banal bacteria. The number of FF varies within a wide range depending on the physicochemical conditions of the habitat. The FF number's dynamics in the soil is of a seasonal nature; i.e., the number of bacteria found increases in the summer and fall and decreases in the winter-spring period. In the rhizosphere of the alfalfa, over the vegetation period, the number of FF and their fraction in the total mass of the bacteria increase. A reverse tendency is observed in the rhizoplane. The morphological particularities (identified by an electron microscopy) and the nature of the FF indicate their physiological activity.

  20. Cytomegalovirus-Associated CD4(+) CD28(null) Cells in NKG2D-Dependent Glomerular Endothelial Injury and Kidney Allograft Dysfunction.

    PubMed

    Shabir, S; Smith, H; Kaul, B; Pachnio, A; Jham, S; Kuravi, S; Ball, S; Chand, S; Moss, P; Harper, L; Borrows, R

    2016-04-01

    Emerging data suggest that expansion of a circulating population of atypical, cytotoxic CD4(+) T cells lacking costimulatory CD28 (CD4(+) CD28(null) cells) is associated with latent cytomegalovirus (CMV) infection. The purpose of the current study was to increase the understanding of the relevance of these cells in 100 unselected kidney transplant recipients followed prospectively for a median of 54 months. Multicolor flow cytometry of peripheral blood mononuclear cells before transplantation and serially posttransplantation was undertaken. CD4(+) CD28(null) cells were found predominantly in CMV-seropositive patients and expanded in the posttransplantation period. These cells were predominantly effector-memory phenotype and expressed markers of endothelial homing (CX3CR1) and cytotoxicity (NKG2D and perforin). Isolated CD4(+) CD27(-) CD28(null) cells proliferated in response to peripheral blood mononuclear cells previously exposed to CMV-derived (but not HLA-derived) antigens and following such priming incubation with glomerular endothelium resulted in signs of endothelial damage and apoptosis (release of fractalkine and von Willebrand factor; increased caspase 3 expression). This effect was mitigated by NKG2D-blocking antibody. Increased CD4(+) CD28(null) cell frequencies were associated with delayed graft function and lower estimated glomerular filtration rate at end follow-up. This study suggests an important role for this atypical cytotoxic CD4(+) CD28(null) cell subset in kidney transplantation and points to strategies that may minimize the impact on clinical outcomes. PMID:26603521

  1. ADVANCED FILTRATION OF PULP MILL WASTES

    EPA Science Inventory

    Laboratory and pilot plants studies of reverse osmosis (hyperfiltration) and ultrafiltration of pulp mill wastes were performed by International Paper Company and Oak Ridge National Laboratory (subcontractor). Decker filtrates were treated with dynamically formed reverse osmosis ...

  2. Coagulation-membrane filtration of Chlorella vulgaris.

    PubMed

    Lee, Duu-Jong; Liao, Guan-Yu; Chang, Yin-Ru; Chang, Jo-Shu

    2012-03-01

    Filtration-based separation of Chlorella vulgaris, a species with excellent potential for CO(2) capture and lipid production, was investigated using a surface-modified hydrophilic polytetrafluoroethylene (PTFE) membrane. Coagulation using polyaluminum chloride (PACl) attained maximum turbidity removal at 200 mg L(-1) as Al(2)O(3). The membrane filtration flux at 1 bar increased as the PACl dose increased, regardless of overdosing in the coagulation stage. The filtered cake at the end of filtration tests peaked in solid content at 10 mg L(-1) as Al(2)O(3), reaching 34% w/w, roughly two times that of the original suspension. Differential scanning calorimetry (DSC) tests demonstrate that the cake with minimum water-solid binding strength produced the driest filter cake. Coagulation using 10 mg L(-1) PACl as Al(2)O(3), followed by PTFE membrane filtration at 1 bar, is an effective process for harvesting C. vulgaris from algal froth. PMID:22261659

  3. MICROBIAL PATHOGEN REMOVAL DURING BANK FILTRATION

    EPA Science Inventory

    Our incomplete understanding of processes and properties affecting pathogenic microbe transport during riverbank filtration is currently limiting our ability to predict the effectiveness of this water treatment option. We propose a series of fundamental experiments designed to...

  4. "Jeopardy" in Abnormal Psychology.

    ERIC Educational Resources Information Center

    Keutzer, Carolin S.

    1993-01-01

    Describes the use of the board game, Jeopardy, in a college level abnormal psychology course. Finds increased student interaction and improved application of information. Reports generally favorable student evaluation of the technique. (CFR)

  5. Abnormal Uterine Bleeding

    MedlinePlus

    ... Abnormal uterine bleeding is any bleeding from the uterus (through your vagina) other than your normal monthly ... or fibroids (small and large growths) in the uterus can also cause bleeding. Rarely, a thyroid problem, ...

  6. Abnormal Uterine Bleeding FAQ

    MedlinePlus

    ... as cancer of the uterus, cervix, or vagina • Polycystic ovary syndrome How is abnormal bleeding diagnosed? Your health care ... before the fetus can survive outside the uterus. Polycystic Ovary Syndrome: A condition characterized by two of the following ...

  7. Coal filtration process and dewatering aids therefore

    SciTech Connect

    Keys, R.O.

    1990-01-09

    This patent describes an improvement in a method for dewatering an aqueous slurry of solid coal particulates wherein the aqueous slurry contains between about 10 and 60 percent of solid coal particulates and a dewatering aid is added to the slurry followed by vacuum filtration thereof to produce a filter cake of the coal particulates. The improvement for lowering the water content of the filter cake comprises adding to the slurry prior to filtration an effective amount of a dewatering aid selected.

  8. Rat olfactory bulb mitral cells receive sparse glomerular inputs.

    PubMed

    Fantana, Antoniu L; Soucy, Edward R; Meister, Markus

    2008-09-11

    Center-surround receptive fields are a fundamental unit of brain organization. It has been proposed that olfactory bulb mitral cells exhibit this functional circuitry, with excitation from one glomerulus and inhibition from a broad field of glomeruli within reach of the lateral dendrites. We investigated this hypothesis using a combination of in vivo intrinsic imaging, single-unit recording, and a large panel of odors. Assuming a broad inhibitory field, a mitral cell would be influenced by >100 contiguous glomeruli and should respond to many odors. Instead, the observed response rate was an order of magnitude lower. A quantitative model indicates that mitral cell responses can be explained by just a handful of glomeruli. These glomeruli are spatially dispersed on the bulb and represent a broad range of odor sensitivities. We conclude that mitral cells do not have center-surround receptive fields. Instead, each mitral cell performs a specific computation combining a small and diverse set of glomerular inputs. PMID:18786363

  9. Histiocytic and Nonhistiocytic Glomerular Lesions: Foam Cells and Their Mimickers.

    PubMed

    Kaur, Amulyajit; Sethi, Sanjeev

    2016-02-01

    Numerous histiocytes are sometimes noted in glomeruli, giving rise to a foamy-appearing glomerulus. Foamy-appearing glomeruli may also be noted in conditions that do not contain numerous histiocytes. These disease entities are rare, have different underlying causes and pathophysiology, and can cause a diagnostic dilemma. We have observed this histiocytic/foamy glomerular change on the kidney biopsy specimen in 5 different disease entities: crystal-storing histiocytosis, histiocytic glomerulopathy associated with macrophage-activating syndrome, thrombotic microangiopathy, lecithin-cholesterol acyltransferase deficiency, and lipoprotein glomerulopathy. We describe and compare the kidney biopsy findings of these histiocytic and foamy-appearing entities. It is important to recognize the kidney biopsy findings of these rare conditions to correctly evaluate and identify the cause and manage these patients. PMID:26606995

  10. Acquired antithrombin III deficiency in patients with glomerular proteinuria.

    PubMed

    Thaler, E; Balzar, E; Kopsa, H; Pinggera, W F

    1978-01-01

    Antithrombin III (AT II/III) was determined immunologically and by means of a heparin cofactor assay in plasma samples and 24-hour urine of 15 patients with various degrees of proteinuria, being predominantly of glomerular origin. In urine the AT II/III concentrations were significantly correlated to the concentrations of albumin, plasminogen and IgG. One third of the patients had AT II/III plasma levels below the normal range. The plasma levels showed a significant inverse correlation to the AT II/III and albumin clearance rates. Similarily, the plasminogen concentrations in plasma were decreased in two thirds of the patients, being inversely correlated to the renal plasminogen clearance values. It is proposed that AT II/III deficiency in the nephrotic syndrome is an important pathogenetic factor in venous thrombosis. PMID:689489

  11. Chromosomal Abnormalities and Schizophrenia

    PubMed Central

    BASSETT, ANNE S.; CHOW, EVA W.C.; WEKSBERG, ROSANNA

    2011-01-01

    Schizophrenia is a common and serious psychiatric illness with strong evidence for genetic causation, but no specific loci yet identified. Chromosomal abnormalities associated with schizophrenia may help to understand the genetic complexity of the illness. This paper reviews the evidence for associations between chromosomal abnormalities and schizophrenia and related disorders. The results indicate that 22q11.2 microdeletions detected by fluorescence in-situ hybridization (FISH) are significantly associated with schizophrenia. Sex chromosome abnormalities seem to be increased in schizophrenia but insufficient data are available to indicate whether schizophrenia or related disorders are increased in patients with sex chromosome aneuploidies. Other reports of chromosomal abnormalities associated with schizophrenia have the potential to be important adjuncts to linkage studies in gene localization. Advances in molecular cytogenetic techniques (i.e., FISH) have produced significant increases in rates of identified abnormalities in schizophrenia, particularly in patients with very early age at onset, learning difficulties or mental retardation, or dysmorphic features. The results emphasize the importance of considering behavioral phenotypes, including adult onset psychiatric illnesses, in genetic syndromes and the need for clinicians to actively consider identifying chromosomal abnormalities and genetic syndromes in selected psychiatric patients. PMID:10813803

  12. Estimating mean glomerular volume using two arbitrary parallel sections.

    PubMed

    Najafian, Behzad; Basgen, John M; Mauer, Michael

    2002-11-01

    The most reliable method for estimation of mean glomerular volume (MGV), the disector/Cavalieri method, is technically demanding and time consuming. Other methods suffer either from a lack of precise correlation with the gold standard or from the need for a large number of glomeruli in the sample. Here, a new method (the 2-profile method) is described; it provides a reliable estimate of MGV by measuring the profile area of glomeruli in two arbitrary parallel sections. MGV was estimated in renal biopsies from 16 diabetic patients and 13 normal subjects using both the Cavalieri and the 2-profile methods. The range of individual glomerular volumes based on the Cavalieri measurements was 0.31 to 4.02 x10(6) micro m(3). There was a high correlation between the two methods for MGV (r = 0.97; P < 0.0001). However, the 2-profile method systematically overestimated MGV (P = 0.0005, paired t test). This overestimation was corrected by introducing a multiplication factor of 0.91, after which statistical criteria of interchangeability with the Cavalieri method were met. The optimal distance between two sections was determined as 20 micro m with a coefficient of variation of 7.4% in repeated measurements of MGV. On the basis of findings that values for MGV stabilize after ten glomeruli are measured by the disector/Cavalieri method, it was determined that the accuracy of MGV by the 2-profile method obtained by eight glomeruli was less than 7% different from ten in all cases. Thus, the 2-profile method is a practical alternative to the disector/Cavalieri method for estimating MGV, especially in small samples and blocks with limited residual tissue. PMID:12397039

  13. Decreased excretion of glycosaminoglycans in patients with primary glomerular diseases.

    PubMed

    Tencer, J; Torffvit, O; Björnsson, S; Thysell, H; Grubb, A; Rippe, B

    1997-10-01

    Urine glycosaminoglycans (GAG) concentrations were measured in 150 patients with primary glomerulonephritides: endocapillary glomerulonephritis, mesangial proliferative glomerulonephritis, IgA nephropathy, membranous glomerulonephritis and minimal change nephropathy, and in 63 healthy controls and 19 patients with diabetes nephropathy. The urine GAG to creatinine ratios (GCR) were significantly reduced (p < 0.01) in all the glomerulonephritides investigated (0.20 mg/mmol in endocapillary glomerulonephritis, 1.60 mg/mmol in mesangial proliferative glomerulonephritis, 1.74 mg/mmol in IgA nephropathy, 1.09 mg/mmol in membranous nephropathy, and 1.16 mg/mmol in minimal change nephropathy) compared to healthy controls (2.87 mg/mmol) but not compared to diabetes patients (1.17 mg/mmol). Also, the GCR in a group of 23 non-albuminuric glomerulonephritis patients (1.98 mg/mmol) was shown to be significantly decreased (p < 0.01) compared to healthy controls. Moreover, the GCR was significantly lower (p < 0.01) in endocapillary glomerulonephritis than in any of the other diseases studied. The GAG excretion per functioning glomerular area, calculated as fractional GAG excretion (FGE), was decreased in all the glomerulonephritides investigated compared to both healthy controls and diabetes nephropathy. The decreased GAG excretion in glomerulonephritides, obtained in the present study, might be a consequence of decreased synthesis or turnover of GAG in the functioning nephrons whereas the mechanisms for the reduced GAG excretion in diabetes nephropathy might be of a different nature. Urinary GAG excretion in this group of glomerular disorders and particularly in endocapillary glomerulonephritis, may lead to new approaches in non-invasive renal diagnostics and, particularly with regard to the differentiation of acute and chronic forms of glomerulonephritides. PMID:9352154

  14. 6. Detail view northeast of rear of filtration bed building. ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    6. Detail view northeast of rear of filtration bed building. Note monitor roof with clerestory windows over central corridor between filtration beds at center right of photograph. Laboratory building is at center right of photograph. - Lake Whitney Water Filtration Plant, Filtration Plant, South side of Armory Street between Edgehill Road & Whitney Avenue, Hamden, New Haven County, CT

  15. 5. View northeast of rear of filtration bed building. Note ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    5. View northeast of rear of filtration bed building. Note monitor roof with clerestory windows over central corridor between filtration beds at center right of photograph. Laboratory building is at extreme center right of photograph. - Lake Whitney Water Filtration Plant, Filtration Plant, South side of Armory Street between Edgehill Road & Whitney Avenue, Hamden, New Haven County, CT

  16. 10. View west of east entry to filtration beds. Note ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    10. View west of east entry to filtration beds. Note monitor roof and clerestory windows over central corridor. Laboratory building is sited over the center of the filtration bed building at extreme left center of photograph. - Lake Whitney Water Filtration Plant, Filtration Plant, South side of Armory Street between Edgehill Road & Whitney Avenue, Hamden, New Haven County, CT

  17. Genetic Background is a Key Determinant of Glomerular Extracellular Matrix Composition and Organization.

    PubMed

    Randles, Michael J; Woolf, Adrian S; Huang, Jennifer L; Byron, Adam; Humphries, Jonathan D; Price, Karen L; Kolatsi-Joannou, Maria; Collinson, Sophie; Denny, Thomas; Knight, David; Mironov, Aleksandr; Starborg, Toby; Korstanje, Ron; Humphries, Martin J; Long, David A; Lennon, Rachel

    2015-12-01

    Glomerular disease often features altered histologic patterns of extracellular matrix (ECM). Despite this, the potential complexities of the glomerular ECM in both health and disease are poorly understood. To explore whether genetic background and sex determine glomerular ECM composition, we investigated two mouse strains, FVB and B6, using RNA microarrays of isolated glomeruli combined with proteomic glomerular ECM analyses. These studies, undertaken in healthy young adult animals, revealed unique strain- and sex-dependent glomerular ECM signatures, which correlated with variations in levels of albuminuria and known predisposition to progressive nephropathy. Among the variation, we observed changes in netrin 4, fibroblast growth factor 2, tenascin C, collagen 1, meprin 1-α, and meprin 1-β. Differences in protein abundance were validated by quantitative immunohistochemistry and Western blot analysis, and the collective differences were not explained by mutations in known ECM or glomerular disease genes. Within the distinct signatures, we discovered a core set of structural ECM proteins that form multiple protein-protein interactions and are conserved from mouse to man. Furthermore, we found striking ultrastructural changes in glomerular basement membranes in FVB mice. Pathway analysis of merged transcriptomic and proteomic datasets identified potential ECM regulatory pathways involving inhibition of matrix metalloproteases, liver X receptor/retinoid X receptor, nuclear factor erythroid 2-related factor 2, notch, and cyclin-dependent kinase 5. These pathways may therefore alter ECM and confer susceptibility to disease. PMID:25896609

  18. Tumor necrosis factor-alpha is expressed by glomerular visceral epithelial cells in human membranous nephropathy.

    PubMed Central

    Neale, T. J.; Rüger, B. M.; Macaulay, H.; Dunbar, P. R.; Hasan, Q.; Bourke, A.; Murray-McIntosh, R. P.; Kitching, A. R.

    1995-01-01

    The role of tumor necrosis factor alpha (TNF-alpha) was examined in biopsy-proven glomerulonephritis by immunohistochemistry, in situ hybridization, immunogold electron microscopy, immunoassay in serum and urine, and urinary immunoblot. Striking glomerular capillary wall and visceral glomerular epithelial cell TNF-alpha protein staining was observed in all cases of membranous nephropathy and membranous lupus nephropathy. Staining was less frequently observed in crescentic glomerulonephritis and in isolated cases of other histological subtypes of glomerulonephritis, usually in association with glomerular macrophages. By immunogold electron microscopy TNF-alpha was localized in membranous nephropathy within the visceral glomerular epithelial cells, and also in the glomerular basement membrane, especially in relation to immune deposits. In situ hybridization localized TNF-alpha mRNA exclusively to glomerular epithelial cells in all biopsies with membranous morphology but not in other histological subtypes. Concentrations of TNF-alpha were significantly increased compared with normal controls in the urine of patients with membranous nephropathy and with crescentic glomerulonephritis. The expression of TNF-alpha by glomerular epithelial cells exclusively and universally in biopsies showing a membranous morphology strongly suggests this cytokine has a role in the pathogenesis of membranous nephropathy. Images Figure 1 Figure 2 Figure 3 Figure 5 PMID:7778683

  19. Subfractionation, characterization and in-depth proteomic analysis of glomerular membrane vesicles in human urine

    PubMed Central

    Hogan, Marie C.; Johnson, Kenneth L.; Zenka, Roman M.; Charlesworth, M. Cristine; Madden, Benjamin J.; Mahoney, Doug W.; Oberg, Ann L.; Huang, Bing Q.; Nesbitt, Lisa L.; Bakeberg, Jason L.; Bergen, H. Robert; Ward, Christopher J.

    2014-01-01

    Urinary exosome-like vesicles (ELVs) are a heterogenous mixture (diameter 40–200nm) containing vesicles shed from all segments of the nephron including glomerular podocytes. Contamination with Tamm Horsfall protein (THP) oligomers has hampered their isolation and proteomic analysis. Here we improved ELV isolation protocols employing density centrifugation to remove THP and albumin, and isolated a glomerular membranous vesicle (GMV) enriched subfraction from 7 individuals identifying 1830 proteins and in 3 patients with glomerular disease identifying 5657 unique proteins. The GMV fraction was composed of podocin/podocalyxin positive irregularly shaped membranous vesicles and podocin/podocalyxin negative classical exosomes. Ingenuity pathway analysis identified integrin, actin cytoskeleton and RhoGDI signaling in the top three canonical represented signaling pathways and 19 other proteins associated with inherited glomerular diseases. The GMVs are of podocyte origin and the density gradient technique allowed isolation in a reproducible manner. We show many nephrotic syndrome proteins, proteases and complement proteins involved in glomerular disease are in GMVs and some were shed in the disease state (nephrin, TRPC6 and INF2 and PLA2R). We calculated sample sizes required to identify new glomerular disease biomarkers, expand the ELV proteome and provide a reference proteome in a database that may prove useful in the search for biomarkers of glomerular disease. PMID:24196483

  20. Identification of Promising Urinary MicroRNA Biomarkers in Two Rat Models of Glomerular Injury.

    PubMed

    Nassirpour, Rounak; Homer, Bruce L; Mathur, Sachin; Li, Yizheng; Li, Zhonghan; Brown, Tom; Carraher, Deborah; Warneke, James; Bailey, Steven; Percival, Karen; O'Neil, Shawn P; Whiteley, Laurence O

    2015-11-01

    MicroRNAs (miRNAs) are small, noncoding RNAs that regulate protein levels posttranscriptionally. miRNAs play important regulatory roles in many cellular processes and have been implicated in several diseases. Recent studies have reported significant levels of miRNAs in a variety of body fluids, raising the possibility that miRNAs could serve as useful biomarkers. Here, changes in miRNA expression patterns are described in 2 different rodent models of glomerular injury (acute puromycin aminonucleoside nephropathy and passive Heymann nephritis). By employing 2 different modes of glomerular insult, oxidative stress and immune-mediated toxicity, miRNA changes in both isolated glomeruli as well as urine specimens allow for identification of urinary miRNA biomarkers that are suggestive of drug-induced injury specifically to the glomerulus. Subsets of glomerular urinary miRNAs associated with these different modes of glomerular toxicity seem to be dependent on the mechanism of the induced injury, while 9 miRNAs that changed early in both glomerular and urine specimens were common to both studies. We further show that the miRNAs identified as mechanism-specific early glomerular injury biomarkers target key pathways and transcripts relevant to the type of insult, while the insult-independent changes might serve as ideal glomerular injury biomarkers. PMID:26253709

  1. Environmental Technology Verification--Baghouse Filtration Products: GE Energy QG061 Filtration Media (Tested September 2008)

    EPA Science Inventory

    This report reviews the filtration and pressure drop performance of GE Energy's QG061 filtration media. Environmental Technology Verification (ETV) testing of this technology/product was conducted during a series of tests in September 2008. The objective of the ETV Program is to ...

  2. Dynamic filtration of invert-emulsion muds

    SciTech Connect

    Jiao, D.; Sharma, M.M. )

    1993-09-01

    Dynamic-filtration experiments conducted on oil-based muds show that the dynamic-filtration rate is much higher than API filtration rates. The use of water-wet solids results in very poor-quality external mudcakes and high fluid-loss rates. Better external mudcakes are formed by mixing equal parts organophilic clay and mud. Filtration-loss-control additives (asphalt mineral pitches) do not reduce the equilibrium filtration rate, but do reduce spurt loss and limit solids invasion. In brine-saturated rocks, the invasion rate for oil-based muds is significantly smaller than for water-based muds because capillary pressure prevents the oil phase from entering the core in oil-based muds. Oil-based mudcakes are softer and more shear-sensitive than water-based mudcakes. Scanning electron microscope (SEM) photomicrographs indicate that oil-based mudcakes consist of individual water droplets coated with clay particles. This cake structure gives rise to the low permeability and shear sensitivity of oil-based muds.

  3. Protective Role of Growth Hormone against Hyperhomocysteinemia Induced Glomerular Injury

    PubMed Central

    Li, Caixia; Xia, Min; Abais, Justine M.; Liu, Xiaocheng; Li, Ningjun; Boini, Krishna M.; Li, Pin-Lan

    2013-01-01

    The present study investigated the protective role of growth hormone (GH) against hyperhomocysteinemia (hHcys)-induced activations of reactive oxygen species (ROS)/hypoxia-inducible factor (HIF)-1α, epithelial-mesenchymal transition (EMT) and consequent glomerular injury. A hyperhomocysteinemia (hHcys) model was induced by folate free (FF) diet in mice. The urine protein excretion significantly increased while plasma GH levels dramatically decreased in hHcys. Real time RT-PCR showed that GH receptor (GHR) level increased in the cortex of hHcys mice, which mainly occurred in podocytes as shown by confocal microscopy. Recombinant mouse growth hormone (rmGH) treatment (0.02 mg/kg, once a day for 6 weeks) significantly restored the plasma GH, inhibited GHR up-regulation and attenuated proteinuria. Correspondingly, rmGH treatment also blocked hHcys-induced decrease in the expression of podocin, a podocyte slit diaphragm molecule, and inhibited the increases in the expression of desmin, a podocyte injury marker. It was also demonstrated that in hHcys the expression of epithelial markers, p-cadherin and ZO-1, decreased, while the expression of mesenchymal markers, FSP-1 and α-SMA, increased in podocytes, which together suggest the activation of EMT in podocytes. NADPH oxidase (Nox)-dependent superoxide anion (O2·−) and HIF-1α level in the hHcys mice cortex was markedly enhanced. These hHcys-induced EMT enhancement and Nox-dependant O2·−/HIF-1α activation were significantly attenuated by rmGH treatment. HIF-1α level increased in Hcys-treated cultured podocytes, which were blocked by rmGH treatment. Meanwhile, Hcys-induced EMT in cultured podocytes was significantly reversed by HIF-1α siRNA. All these results support the view that GH ameliorates hHcys-induced glomerular injury by reducing Nox-dependent O2·−/HIF-1α signal pathway and EMT. PMID:23529346

  4. Identification of a major sialoprotein in the glycocalyx of human visceral glomerular epithelial cells.

    PubMed

    Kerjaschki, D; Poczewski, H; Dekan, G; Horvat, R; Balzar, E; Kraft, N; Atkins, R C

    1986-11-01

    Glomerular visceral epithelial cells are endowed with a sialic acid-rich surface coat (the "glomerular epithelial polyanion"), which in rat tissue contains the sialoprotein podocalyxin. We have identified a major membrane sialoprotein in human glomeruli that is similar to rat podocalyxin in its sialic acid-dependent binding of wheat germ agglutinin and in its localization on the surface of glomerular epithelial and endothelial cells, as shown by immunoelectron microscopy, using the monoclonal antibody PHM5. Differences in the sialoproteins of the two species are indicated by the discrepancy of their apparent molecular weights in sodium dodecyl sulfate gels, by the lack of cross reactivity of their specific antibodies, and by the lack of homology of their proteolytic peptide maps. It is therefore possible that the human glomerular sialoprotein and rat podocalyxin are evolutionarily distinct, but have similar functions. PMID:3533998

  5. High-efficiency filtration meets IAQ goals

    SciTech Connect

    Aaronson, E.L. ); Fencl, F. )

    1994-12-01

    This article describes multi-stage filtration system which provided initial cost savings and is expected to save even more in energy costs while fulfilling IAQ requirements. The use of high-efficiency filtration has enabled the city of Kansas City, Mo., to save an estimated $500,000 in initial HVAC system costs for its Bartle Hall expansion project, which is currently under construction. Once operational, the new HVAC system, with its high-efficiency filters, is expected to save thousands of dollars per week more in energy costs while also delivering superior indoor air quality (IAQ).

  6. Filtration of a Hanford AN-104 Sample

    SciTech Connect

    POIRIER, MICHAEL

    2004-04-19

    The Savannah River Technology Center (SRTC) conducted ultrafiltration tests with samples from the Hanford Site's 241-AN-104 tank. The test objectives were to measure filter flux during dewatering and the removal of soluble species during washing. The filtration tests were conducted with the Cells Unit Filter (CUF) currently installed in Cell 16 of the SRTC High Activity Caves. Following filtration, personnel performed inhibited water washing to remove soluble species. Because of the limited volume of concentrated slurry, the washing was performed with a volumetric flask rather than a crossflow filter. Following the washing, personnel chemically cleaned the filter with 1 M nitric acid and periodically measured the clean water flux.

  7. Filtration of A Hanford AN-104 Sample

    SciTech Connect

    Poirier, MichaelR

    2004-03-01

    The Savannah River Technology Center (SRTC) conducted ultrafiltration tests with samples from the Hanford Site's AN-104 tank. The test objectives were to measure filter flux during dewatering and the removal of soluble species during washing. The filtration tests were conducted with the Cells Unit Filter (CUF) currently installed in Cell 16 of the SRTC High Activity Caves. Following filtration, personnel performed inhibited water washing to remove soluble species. Because of the limited volume of concentrated slurry, the washing was performed with a volumetric flask rather than a crossflow filter.Following the washing, personnel chemically cleaned the filter with 1 M nitric acid and periodically measured the clean water flux.

  8. Quantifying oil filtration effects on bearing life

    NASA Technical Reports Server (NTRS)

    Needelman, William M.; Zaretsky, Erwin V.

    1991-01-01

    Rolling-element bearing life is influenced by the number, size, and material properties of particles entering the Hertzian contact of the rolling element and raceway. In general, rolling-element bearing life increases with increasing level of oil filtration. Based upon test results, two equations are presented which allow for the adjustment of bearing L(sub 10) or catalog life based upon oil filter rating. It is recommended that where no oil filtration is used catalog life be reduced by 50 percent.

  9. Vacuum distillation/vapor filtration water recovery

    NASA Technical Reports Server (NTRS)

    Honegger, R. J.; Neveril, R. B.; Remus, G. A.

    1974-01-01

    The development and evaluation of a vacuum distillation/vapor filtration (VD/VF) water recovery system are considered. As a functional model, the system converts urine and condensates waste water from six men to potable water on a steady-state basis. The system is designed for 180-day operating durations and for function on the ground, on zero-g aircraft, and in orbit. Preparatory tasks are summarized for conducting low gravity tests of a vacuum distillation/vapor filtration system for recovering water from urine.

  10. The Perspective of Riverbank Filtration in China

    NASA Astrophysics Data System (ADS)

    Li, J.; Teng, Y.; Zhai, Y.; Zuo, R.

    2014-12-01

    Sustainable drinking water supply can affect the health of people, and the surrounding ecosystems. According to statistics of the monitoring program of drinking water sources in 309 at or above prefecture level of China in 2013, the major pollutants index were total phosphorus, ammonia and manganese in surface drinking water sources, respectively, iron, ammonia and manganese in groundwater drinking water sources, respectively. More than 150 drinking water emergency environmental accidents happened since 2006, 52 of these accidents led to the disruption of water supply in waterworks, and a population of over ten million were affected. It indicated that there is a potential risk for people's health by the use of river water directly and it is necessary to require alternative techniques such as riverbank filtration for improving the drinking water quality. Riverbank filtration is an inexpensive natural process, not only smoothing out normal pollutant concentration found in surface water but also significantly reducing the risk from such emergency events as chemical spill into the river. Riverbank filtration technique has been used in many countries more than 100 years, including China. In China, in 1950s, the bank infiltration technique was first applied in northeast of China. Extensive bank infiltration application was conducted in 1980s, and more than 300 drinking water sources utilities bank infiltration established mainly near the Songhua River Basin, the Yellow River Basin, Haihe River Basin. However, the comparative lack of application and researches on riverbank filtration have formed critical scientific data gap in China. As the performance of riverbank filtration technique depend on not only the design and setting such as well type, pumping rate, but also the local hydrogeology and environmental properties. We recommend more riverbank filtration project and studies to be conducted to collect related significant environmental geology data in China

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

    PubMed

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

    2016-05-01

    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. PMID:26847362

  12. The glomerular permeability factors in idiopathic nephrotic syndrome.

    PubMed

    Davin, Jean-Claude

    2016-02-01

    It is currently postulated that steroid-sensitive idiopathic nephrotic syndrome (SSNS) and steroid-resistant idiopathic nephrotic syndrome (SRNS), which are not related to the mutation of a gene coding for podocyte structures or for glomerular basement membrane proteins, result from a circulating factor affecting podocyte shape and function. T lymphocytes have for a long time been suspected to be involved in the pathophysiology of these diseases. The successful treatment of steroid-dependant nephrotic syndrome with rituximab suggests a potential role for B lymphocytes. Clinical and experimental data indicate roles for cytokines IL-13, TNFα, circulating cardiotrophin-like cytokine factor 1 (member of the IL-6 family), circulating hemopexin, radical oxygen species, and the soluble urokinase-type plasminogen activator receptor (suPAR) in the development of nephrotic syndrome. Podocyte metabolism modifications-leading to the overexpression of the podocyte B7-1antigen (CD 80), hypoactivity of the podocyte enzyme sphingomyelin phosphodiesterase acid-like 3 b (SMPDL3b), and to the podocyte production of a hyposialylated form of the angiopoietin-like 4 (Angptl4)-are mechanisms possibly involved in the changes in the podocyte cytoskeleton leading to SSNS and or SRNS. Different multifactorial pathophysiological mechanisms can be advocated for SSNS and SRNS. The present paper reviews the experimental and clinical data upon which the different hypotheses are based and reports their possible clinical applications. PMID:25925039

  13. Unaltered anionic sites of glomerular basement membrane in aminonucleoside nephrosis

    SciTech Connect

    Kanwar, Y.S.; Jakubowski, M.L.

    1984-04-01

    Quantitative electron microscopic autoradiography was employed to determine the changes in the binding of /sup 125/I-cationic ferritin (CFI, pI approximately 7.2 to 7.4) to the anionic sites of the glomerular basement membrane (GBM) of rats following the induction of nephrosis. Animals were rendered nephrotic by a single intravenous injection of puromycin aminonucleoside (PAN) and sacrificed 0, 7, 14, and 21 days after its administration. CFI (10 mg/mCi/100 g body weight) was given intravenously. The kidneys were subsequently fixed by perfusion and processed for electron microscopic autoradiography. The mean grain densities over the GBMs on 0, 7, 14, and 21 days of PAN nephrosis were 1.50 +/- 0.04, 1.49 +/- 0.05, 1.50 +/- 0.05, and 1.51 +/- 0.04, respectively. These results indicate that there are no significant alterations in the anionic sites rich in heparan sulfate proteoglycan during the entire course of PAN nephrosis.

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

    PubMed

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

    2015-04-01

    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. PMID:25667164

  15. Anionic charge concentration of rat kidney glomeruli and glomerular basement membrane.

    PubMed Central

    Comper, W D; Lee, A S; Tay, M; Adal, Y

    1993-01-01

    Estimates of levels of glomerular and glomerular-basement-membrane anion charge should serve as useful quantitative markers for the integrity of the tissues in health and disease. We have developed a simple, rapid, technique to measure this charge through the use of ion exchange with radioisotopes 22Na+ and 36Cl- at low ionic strengths in phosphate buffer. When this technique is used, normal glomeruli isolated from rat have a measured net anion charge concentration of 17.4 +/- 3.7 p-equiv. per glomerulus (n = 20). Perfused rat kidneys that lose approximately half of their glomerular heparan [35S]sulphate content (owing to oxygen-radical damage) exhibited a lower anion charge, of 7.5 +/- 1.6 p-equiv. per glomerulus (n = 5). Glomerular basement membranes prepared from rat glomeruli by a sonication-centrifugation procedure in the presence of enzyme inhibitors had a charge concentration of 6.3 +/- 0.7 mu-equiv./g wet wt. of tissue (n = 4), whereas membranes prepared by sonication, centrifugation, DNAse and detergent treatment had a charge concentration of 7.1 +/- 1.6 mu-equiv./g wet wt. (n = 4). Isotope-dilution experiments with 3H2O on these detergent-prepared glomerular basement membranes demonstrated that they had a water content of approx. 93%, which would then give a net anion charge concentration of 7.6 +/- 1.7 m-equiv./l (n = 4). These values are in good agreement with those obtained by others using titration techniques [Bray and Robinson (1984) Kidney Int. 25, 527-533]. The relatively low magnitude of glomerular anion charge in normal kidneys is consistent with other recent findings that glomerular anion charge is too low to affect the glomerular transport of charged molecules in a direct, passive, biophysical manner through electrostatic interactions. PMID:8435064

  16. Habituation of glomerular responses in the olfactory bulb following prolonged odor stimulation reflects reduced peripheral input

    PubMed Central

    Ogg, M. Cameron; Bendahamane, Mounir; Fletcher, Max L.

    2015-01-01

    Following prolonged odor stimulation, output from olfactory bulb (OB) mitral/tufted (M/T) cells is decreased in response to subsequent olfactory stimulation. Currently, it is unclear if this decrease is a function of adaptation of peripheral olfactory sensory neuron (OSN) responses or reflects depression of bulb circuits. We used wide-field calcium imaging in anesthetized transgenic GCaMP2 mice to compare excitatory glomerular layer odor responses before and after a 30-s odor stimulation. Significant habituation of subsequent glomerular odor responses to both the same and structurally similar odorants was detected with our protocol. To test whether depression of OSN terminals contributed to this habituation, olfactory nerve layer (ON) stimulation was used to drive glomerular layer responses in the absence of peripheral odor activation of the OSNs. Following odor habituation, in contrast to odor-evoked glomerular responses, ON stimulation-evoked glomerular responses were not habituated. The difference in response between odor and electrical stimulation following odor habituation provides evidence that odor response reductions measured in the glomerular layer of the OB are most likely the result of OSN adaptation processes taking place in the periphery. PMID:26441516

  17. Increased olfactory bulb acetylcholine bi-directionally modulates glomerular odor sensitivity

    PubMed Central

    Bendahmane, Mounir; Ogg, M. Cameron; Ennis, Matthew; Fletcher, Max L.

    2016-01-01

    The glomerular layer of the olfactory bulb (OB) receives heavy cholinergic input from the horizontal limb of the diagonal band of Broca (HDB) and expresses both muscarinic and nicotinic acetylcholine (ACh) receptors. However, the effects of ACh on OB glomerular odor responses remain unknown. Using calcium imaging in transgenic mice expressing the calcium indicator GCaMP2 in the mitral/tufted cells, we investigated the effect of ACh on the glomerular responses to increasing odor concentrations. Using HDB electrical stimulation and in vivo pharmacology, we find that increased OB ACh leads to dynamic, activity-dependent bi-directional modulation of glomerular odor response due to the combinatorial effects of both muscarinic and nicotinic activation. Using pharmacological manipulation to reveal the individual receptor type contributions, we find that m2 muscarinic receptor activation increases glomerular sensitivity to weak odor input whereas nicotinic receptor activation decreases sensitivity to strong input. Overall, we found that ACh in the OB increases glomerular sensitivity to odors and decreases activation thresholds. This effect, along with the decreased responses to strong odor input, reduces the response intensity range of individual glomeruli to increasing concentration making them more similar across the entire concentration range. As a result, odor representations are more similar as concentration increases. PMID:27165547

  18. World Small Animal Veterinary Association Renal Pathology Initiative: Classification of Glomerular Diseases in Dogs.

    PubMed

    Cianciolo, R E; Mohr, F C; Aresu, L; Brown, C A; James, C; Jansen, J H; Spangler, W L; van der Lugt, J J; Kass, P H; Brovida, C; Cowgill, L D; Heiene, R; Polzin, D J; Syme, H; Vaden, S L; van Dongen, A M; Lees, G E

    2016-01-01

    Evaluation of canine renal biopsy tissue has generally relied on light microscopic (LM) evaluation of hematoxylin and eosin-stained sections ranging in thickness from 3 to 5 µm. Advanced modalities, such as transmission electron microscopy (TEM) and immunofluorescence (IF), have been used sporadically or retrospectively. Diagnostic algorithms of glomerular diseases have been extrapolated from the World Health Organization classification scheme for human glomerular disease. With the recent establishment of 2 veterinary nephropathology services that evaluate 3-µm sections with a panel of histochemical stains and routinely perform TEM and IF, a standardized objective species-specific approach for the diagnosis of canine glomerular disease was needed. Eight veterinary pathologists evaluated 114 parameters (lesions) in renal biopsy specimens from 89 dogs. Hierarchical cluster analysis of the data revealed 2 large categories of glomerular disease based on the presence or absence of immune complex deposition: The immune complex-mediated glomerulonephritis (ICGN) category included cases with histologic lesions of membranoproliferative or membranous patterns. The second category included control dogs and dogs with non-ICGN (glomerular amyloidosis or focal segmental glomerulosclerosis). Cluster analysis performed on only the LM parameters led to misdiagnosis of 22 of the 89 cases-that is, ICGN cases moved to the non-ICGN branch of the dendrogram or vice versa, thereby emphasizing the importance of advanced diagnostic modalities in the evaluation of canine glomerular disease. Salient LM, TEM, and IF features for each pattern of disease were identified, and a preliminary investigation of related clinicopathologic data was performed. PMID:25957358

  19. Differentiating Glomerular Inflammation from Fibrosis in A Bone Marrow Chimera for Rat Anti-GBM Glomerulonephritis

    PubMed Central

    Zhou, Cindy; Lou, Kristie; Tatum, Kiana; Funk, Jeremiah; Wu, Jean; Bartkowiak, Todd; Kagan, David; Lou, Yahuan

    2015-01-01

    Background Many types of glomerulonephritis (GN) undergo tandem connected phases: inflammation and fibrosis. Fibrosis in human GNs leads to irreversible end stage disease. This study investigated how these two phases were controlled. Methods Using a rat anti-glomerular basement membrane (GBM) GN model, we established bone marrow (BM) chimeras between GN-resistant Lewis (LEW) and GN-susceptible Wistar Kyoto (WKY) rats. Glomerular inflammation and fibrosis were compared between chimeras. Results LEW’s BM to WKY (WKYLEW) chimeras with or without co-transfer of host WKY’s T cells were GN-resistant. On the other hand, WKY’s BM to LEW (LEWWKY) chimeras developed glomerular inflammation and albuminuria upon immunization. Quantitative analysis showed that the number and composition of inflammatory cells in glomeruli of immunized LEWWKY chimeras were similar to those in immunized WKY rats at their inflammatory peak. Thus, glomerular inflammation was controlled by BM derived non-T cell populations. However, unlike WKY rats, LEWWKY rats did not develop fibrosis until the end of experiments (84 days) in spite of persistent inflammation and albuminuria. Conclusion Inflammation alone was not sufficient to trigger fibrosis, suggesting a critical role of glomerular cells in the fibrotic process. As LEWWKY chimera allows us to separate glomerular inflammation from fibrosis, this model provides a useful tool to study how fibrosis is initiated following inflammation. PMID:26337665

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

    PubMed Central

    Fletcher, Max L.

    2012-01-01

    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 (M/T) cell glomerular activity at the upper level of the OB. 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 (M/T) 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 (M/T) 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 OB by enhancing responses to the learned odor in some glomeruli. PMID:22461771

  1. Deficiency of the Planar Cell Polarity Protein Vangl2 in Podocytes Affects Glomerular Morphogenesis and Increases Susceptibility to Injury

    PubMed Central

    Rocque, Brittany L.; Babayeva, Sima; Li, Jane; Leung, Vicki; Nezvitsky, Lisa; Cybulsky, Andrey V.; Gros, Philippe

    2015-01-01

    The planar cell polarity (PCP) signaling pathway is crucial for tissue morphogenesis. Van Gogh-like protein 2 (Vangl2) is central in the PCP pathway; in mice, Vangl2 loss is embryonically lethal because of neural tube defects, and mutations in Vangl2 are associated with human neural tube defects. In the kidney, PCP signaling may be important for tubular morphogenesis and organization of glomerular epithelial cells (podocytes) along the glomerular basement membrane. Podocyte cell protrusions (foot processes) are critical for glomerular permselectivity; loss of foot process architecture results in proteinuria and FSGS. Previously, we showed a profound effect of PCP signaling on podocyte shape, actin rearrangement, cell motility, and nephrin endocytosis. To test our hypothesis that the PCP pathway is involved in glomerular development and function and circumvent lethality of the ubiquitous Vangl2 mutation in the Looptail mouse, we generated a mouse model with a podocyte-specific ablation of the Vangl2 gene. We report here that podocyte-specific deletion of Vangl2 leads to glomerular maturation defects in fetal kidneys. In adult mice, we detected significantly smaller glomeruli, but it did not affect glomerular permselectivity in aging animals. However, in the context of glomerular injury induced by injection of antiglomerular basement membrane antibody, deletion of Vangl2 resulted in exacerbation of injury and accelerated progression to chronic segmental and global glomerular sclerosis. Our results indicate that Vangl2 function in podocytes is important for glomerular development and protects against glomerular injury in adult animals. PMID:25145929

  2. Cells of Renin Lineage Are Progenitors of Podocytes and Parietal Epithelial Cells in Experimental Glomerular Disease

    PubMed Central

    Pippin, Jeffrey W.; Sparks, Matthew A.; Glenn, Sean T.; Buitrago, Sandra; Coffman, Thomas M.; Duffield, Jeremy S.; Gross, Kenneth W.; Shankland, Stuart J.

    2014-01-01

    Glomerular injury leads to podocyte loss, a process directly underlying progressive glomerular scarring and decline of kidney function. The inherent repair process is limited by the inability of podocytes to regenerate. Cells of renin lineage residing alongside glomerular capillaries are reported to have progenitor capacity. We investigated whether cells of renin lineage can repopulate the glomerulus after podocyte injury and serve as glomerular epithelial cell progenitors. Kidney cells expressing renin were genetically fate-mapped in adult Ren1cCreER×Rs-tdTomato-R, Ren1cCre×Rs-ZsGreen-R, and Ren1dCre×Z/EG reporter mice. Podocyte depletion was induced in all three cell-specific reporter mice by cytotoxic anti-podocyte antibodies. After a decrease in podocyte number, a significant increase in the number of labeled cells of renin lineage was observed in glomeruli in a focal distribution along Bowman's capsule, within the glomerular tuft, or in both locations. A subset of cells lining Bowman's capsule activated expression of the glomerular parietal epithelial cell markers paired box protein PAX2 and claudin-1. A subset of labeled cells within the glomerular tuft expressed the podocyte markers Wilms tumor protein 1, nephrin, podocin, and synaptopodin. Neither renin mRNA nor renin protein was detected de novo in diseased glomeruli. These findings provide initial evidence that cells of renin lineage may enhance glomerular regeneration by serving as progenitors for glomerular epithelial cells in glomerular disease characterized by podocyte depletion. PMID:23769837

  3. Contamination control through filtration of microorganisms

    NASA Technical Reports Server (NTRS)

    Stabekis, P. D.; Lyle, R. G.

    1972-01-01

    A description is given of the various kinds of gas and liquid filters used in decontamination and sterilization procedures. Also discussed are filtration mechanisms, characteristics of filter materials, and the factors affecting filter performance. Summaries are included for filter testing and evaluation techniques and the possible application of the filters to spacecraft sterilization.

  4. Design parameters for rotating cylindrical filtration

    NASA Technical Reports Server (NTRS)

    Schwille, John A.; Mitra, Deepanjan; Lueptow, Richard M.

    2002-01-01

    Rotating cylindrical filtration displays significantly reduced plugging of filter pores and build-up of a cake layer, but the number and range of parameters that can be adjusted complicates the design of these devices. Twelve individual parameters were investigated experimentally by measuring the build-up of particles on the rotating cylindrical filter after a fixed time of operation. The build-up of particles on the filter depends on the rotational speed, the radial filtrate flow, the particle size and the gap width. Other parameters, such as suspension concentration and total flow rate are less important. Of the four mechanisms present in rotating filters to reduce pore plugging and cake build-up, axial shear, rotational shear, centrifugal sedimentation and vortical motion, the evidence suggests rotational shear is the dominant mechanism, although the other mechanisms still play minor roles. The ratio of the shear force acting parallel to the filter surface on a particle to the Stokes drag acting normal to the filter surface on the particle due to the difference between particle motion and filtrate flow can be used as a non-dimensional parameter that predicts the degree of particle build-up on the filter surface for a wide variety of filtration conditions. c2002 Elsevier Science B.V. All rights reserved.

  5. Gel Filtration Chromatography: A Laboratory Experiment.

    ERIC Educational Resources Information Center

    Hurlbut, Jeffrey A.; Schonbeck, Niels D.

    1984-01-01

    Describes a rapid, visual demonstration of protein separation by gel filtration chromatography. The procedure separates two highly colored proteins of different molecular weights on a Sephadex G-75 in 45 minutes. This time includes packing the column as well. Background information, reagents needed, procedures used, and results obtained are…

  6. ELECTROSTATIC STIMULATION OF FABRIC FILTRATION - AN UPDATE

    EPA Science Inventory

    The paper gives results of an investigation of the concept of electrostatic stimulation of fabric filtration (ESFF) on a slipstream of a pulverized-coal-fired boiler using reverse-air-cleaned woven fiberglass filter bags. Operation was demonstrated using ESFF at a glass-to-cloth ...

  7. Plasma discharge self-cleaning filtration system

    DOEpatents

    Cho, Young I.; Fridman, Alexander; Gutsol, Alexander F.; Yang, Yong

    2014-07-22

    The present invention is directed to a novel method for cleaning a filter surface using a plasma discharge self-cleaning filtration system. The method involves utilizing plasma discharges to induce short electric pulses of nanoseconds duration at high voltages. These electrical pulses generate strong Shockwaves that disintegrate and dislodge particulate matter located on the surface of the filter.

  8. DEMONSTRATION BULLETIN: MEMBRANE FILTRATION - SBP TECHNOLOGIES, INC.

    EPA Science Inventory

    SBP Technologies Inc. (SBP) has developed a membrane-based separation technology that can reduce the volume of contaminated groundwater requiring treatment. The SBP Filtration Unit consists of porous, sintered, stainless steel tubes arranged in a shell-and-tube module configurati...

  9. FILTRATION PARAMETERS FOR DUST CLEANING FABRICS

    EPA Science Inventory

    The report describes laboratory and pilot scale testing of bag filter fabrics. Filtration performance data and mathematical modeling parameters are given for four Polish fabrics tested with cement dust, coal dust, flyash, and talc. Conclusions include: (1) The process of clean ai...

  10. Morphological abnormalities in elasmobranchs.

    PubMed

    Moore, A B M

    2015-08-01

    A total of 10 abnormal free-swimming (i.e., post-birth) elasmobranchs are reported from The (Persian-Arabian) Gulf, encompassing five species and including deformed heads, snouts, caudal fins and claspers. The complete absence of pelvic fins in a milk shark Rhizoprionodon acutus may be the first record in any elasmobranch. Possible causes, including the extreme environmental conditions and the high level of anthropogenic pollution particular to The Gulf, are briefly discussed. PMID:25903257

  11. Chromosome abnormalities in glioma

    SciTech Connect

    Li, Y.S.; Ramsay, D.A.; Fan, Y.S.

    1994-09-01

    Cytogenetic studies were performed in 25 patients with gliomas. An interesting finding was a seemingly identical abnormality, an extra band on the tip of the short arm of chromosome 1, add(1)(p36), in two cases. The abnormality was present in all cells from a patient with a glioblastoma and in 27% of the tumor cells from a patient with a recurrent irradiated anaplastic astrocytoma; in the latter case, 7 unrelated abnormal clones were identified except 4 of those clones shared a common change, -Y. Three similar cases have been described previously. In a patient with pleomorphic astrocytoma, the band 1q42 in both homologues of chromosome 1 was involved in two different rearrangements. A review of the literature revealed that deletion of the long arm of chromosome 1 including 1q42 often occurs in glioma. This may indicate a possible tumor suppressor gene in this region. Cytogenetic follow-up studies were carried out in two patients and emergence of unrelated clones were noted in both. A total of 124 clonal breakpoints were identified in the 25 patients. The breakpoints which occurred three times or more were: 1p36, 1p22, 1q21, 1q25, 3q21, 7q32, 8q22, 9q22, 16q22, and 22q13.

  12. [Congenital foot abnormalities].

    PubMed

    Delpont, M; Lafosse, T; Bachy, M; Mary, P; Alves, A; Vialle, R

    2015-03-01

    The foot may be the site of birth defects. These abnormalities are sometimes suspected prenatally. Final diagnosis depends on clinical examination at birth. These deformations can be simple malpositions: metatarsus adductus, talipes calcaneovalgus and pes supinatus. The prognosis is excellent spontaneously or with a simple orthopedic treatment. Surgery remains outstanding. The use of a pediatric orthopedist will be considered if malposition does not relax after several weeks. Malformations (clubfoot, vertical talus and skew foot) require specialized care early. Clubfoot is characterized by an equine and varus hindfoot, an adducted and supine forefoot, not reducible. Vertical talus combines equine hindfoot and dorsiflexion of the forefoot, which is performed in the midfoot instead of the ankle. Skew foot is suspected when a metatarsus adductus is resistant to conservative treatment. Early treatment is primarily orthopedic at birth. Surgical treatment begins to be considered after walking age. Keep in mind that an abnormality of the foot may be associated with other conditions: malposition with congenital hip, malformations with syndromes, neurological and genetic abnormalities. PMID:25524290

  13. FILTRATION OF 'GIARDIA' CYSTS AND OTHER SUBSTANCES. VOLUME 1. DIATOMACEOUS EARTH FILTRATION

    EPA Science Inventory

    The effectiveness of diatomaceous earth filtration of drinking water was studied under various operating conditions for removal of Giardia cysts, total coliform bacteria, standard plate count bacteria, turbidity, and particles. Seven grades of diatomaceous earth were used. Temper...

  14. Abnormal pressures as hydrodynamic phenomena

    USGS Publications Warehouse

    Neuzil, C.E.

    1995-01-01

    So-called abnormal pressures, subsurface fluid pressures significantly higher or lower than hydrostatic, have excited speculation about their origin since subsurface exploration first encountered them. Two distinct conceptual models for abnormal pressures have gained currency among earth scientists. The static model sees abnormal pressures generally as relict features preserved by a virtual absence of fluid flow over geologic time. The hydrodynamic model instead envisions abnormal pressures as phenomena in which flow usually plays an important role. This paper develops the theoretical framework for abnormal pressures as hydrodynamic phenomena, shows that it explains the manifold occurrences of abnormal pressures, and examines the implications of this approach. -from Author

  15. 7. WEYMOUTH FILTRATION PLANT, BUILDING 1 INTERIOR: LA VERNE CONTROL ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    7. WEYMOUTH FILTRATION PLANT, BUILDING 1 INTERIOR: LA VERNE CONTROL ROOM, REGULATES DISTRIBUTION OF WATER, CONTROLS POWER HOUSES. - F. E. Weymouth Filtration Plant, 700 North Moreno Avenue, La Verne, Los Angeles County, CA

  16. 9. VIEW OF UPPER LEVEL OF FILTRATION ROOM SHOWING TANKS ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    9. VIEW OF UPPER LEVEL OF FILTRATION ROOM SHOWING TANKS AND CONTROL VALVES, LOOKING NORTH - Presidio Water Treatment Plant, Filtration Plant, East of Lobos Creek at Baker Beach, San Francisco, San Francisco County, CA

  17. 12. OBLIQUE VIEW OF NORTH WORK ROOM IN FILTRATION PLANT ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    12. OBLIQUE VIEW OF NORTH WORK ROOM IN FILTRATION PLANT (#1773), LOOKING NORTHWEST - Presidio Water Treatment Plant, Filtration Plant, East of Lobos Creek at Baker Beach, San Francisco, San Francisco County, CA

  18. 11. DETAIL VIEW OF FILTER TANK IN FILTRATION PLANT (#1773), ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    11. DETAIL VIEW OF FILTER TANK IN FILTRATION PLANT (#1773), LOOKING NORTHWEST - Presidio Water Treatment Plant, Filtration Plant, East of Lobos Creek at Baker Beach, San Francisco, San Francisco County, CA

  19. Feeling Abnormal: Simulation of Deviancy in Abnormal and Exceptionality Courses.

    ERIC Educational Resources Information Center

    Fernald, Charles D.

    1980-01-01

    Describes activity in which student in abnormal psychology and psychology of exceptional children classes personally experience being judged abnormal. The experience allows the students to remember relevant research, become sensitized to the feelings of individuals classified as deviant, and use caution in classifying individuals as abnormal.…

  20. Participation of glomerular endothelial cells in the capillary repair of glomerulonephritis.

    PubMed Central

    Iruela-Arispe, L.; Gordon, K.; Hugo, C.; Duijvestijn, A. M.; Claffey, K. P.; Reilly, M.; Couser, W. G.; Alpers, C. E.; Johnson, R. J.

    1995-01-01

    In many glomerular diseases severe injury to the mesangium may occur, leading to matrix dissolution and damage to the glomerular capillaries. Although the destruction of glomerular architecture may lead to permanent injury, in some cases spontaneous recovery occurs. The mechanisms that mediate this recovery are unknown. In this study we provide evidence for glomerular capillary repair (angiogenesis) in the adult injured glomerulus. Injection of anti-Thy 1 antibody into rats results in severe mesangiolysis with capillary ballooning, microaneurysm formation, and loss of endothelial cells in addition to mesangial cells. Although mesangial proliferation is a major response to injury, proliferation of endothelial cells also can be documented from days 2 to 14 in association with repair of the capillaries. The endothelial cell proliferation peaks on days 2 and 7, when it is seven- to ninefold greater than normal. Many of the endothelial cells display morphological features of angiogenesis. The initial wave of endothelial cell proliferation can be reduced by 40% with neutralizing anti-basic fibroblast growth factor antibodies (P < 0.001). The later glomerular endothelial cell proliferation is associated with upregulated expression of vascular permeability factor/endothelial cell growth factor (VPF/VEGF) and an increase of flk, a VPF/VEGF receptor. Although PDGF is expressed in this model, anti-PDGF antibody treatment did not affect the endothelial cell proliferative response. In summary, glomerular endothelial cells have an active role in the glomerular response to injury. Glomeruli are capable of healing microaneurysms, and the mechanism involves basic fibroblast growth factor- and VPF/VEGF-mediated endothelial proliferative responses. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 6 PMID:7495296

  1. 21. Overflow pipe in filtration bed. Located at each corner ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    21. Overflow pipe in filtration bed. Located at each corner of the bed, the pipes drain off any excess water and maintain a limit on water depth. - Lake Whitney Water Filtration Plant, Filtration Plant, South side of Armory Street between Edgehill Road & Whitney Avenue, Hamden, New Haven County, CT

  2. 15. View west of central corridor between filtration beds which ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    15. View west of central corridor between filtration beds which are located to the left and right of the photograph. - Lake Whitney Water Filtration Plant, Filtration Plant, South side of Armory Street between Edgehill Road & Whitney Avenue, Hamden, New Haven County, CT

  3. 2. View east of filtration bed building. Access bridge to ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    2. View east of filtration bed building. Access bridge to earth covering over reinforced concrete roof is at center right of photograph. - Lake Whitney Water Filtration Plant, Filtration Plant, South side of Armory Street between Edgehill Road & Whitney Avenue, Hamden, New Haven County, CT

  4. 22. Float located adjacent to entry stair in filtration bed. ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    22. Float located adjacent to entry stair in filtration bed. The float actuates a valve that maintains water level over the bed. - Lake Whitney Water Filtration Plant, Filtration Plant, South side of Armory Street between Edgehill Road & Whitney Avenue, Hamden, New Haven County, CT

  5. 30. Valves under central corridor of filtration bed building. Main ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    30. Valves under central corridor of filtration bed building. Main flood valves is at left and crossover valve is a right. - Lake Whitney Water Filtration Plant, Filtration Plant, South side of Armory Street between Edgehill Road & Whitney Avenue, Hamden, New Haven County, CT

  6. 3. View southeast of northwest corner of filtration bed. Laboratory ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    3. View southeast of northwest corner of filtration bed. Laboratory building is at center right of photograph. East rock appears directly behind the laboratory building. - Lake Whitney Water Filtration Plant, Filtration Plant, South side of Armory Street between Edgehill Road & Whitney Avenue, Hamden, New Haven County, CT

  7. 16. View west from center of central corridor between filtration ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    16. View west from center of central corridor between filtration beds which are located to the left and right of the photograph. - Lake Whitney Water Filtration Plant, Filtration Plant, South side of Armory Street between Edgehill Road & Whitney Avenue, Hamden, New Haven County, CT

  8. 20. View of sand filtration bed. Wheelbarrow was used to ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    20. View of sand filtration bed. Wheelbarrow was used to remove schmutzdeck (top, dirty sand layer containing particulate contamination, dead microorganisms and debris) for cleaning and or disposal. - Lake Whitney Water Filtration Plant, Filtration Plant, South side of Armory Street between Edgehill Road & Whitney Avenue, Hamden, New Haven County, CT

  9. 40 CFR 141.71 - Criteria for avoiding filtration.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 24 2012-07-01 2012-07-01 false Criteria for avoiding filtration. 141.71 Section 141.71 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS (CONTINUED) NATIONAL PRIMARY DRINKING WATER REGULATIONS Filtration and Disinfection § 141.71 Criteria for avoiding filtration. A public...

  10. EFFECT OF PARAMETERS OF FILTRATION ON DUST CLEANING FABRICS

    EPA Science Inventory

    The report summarizes 4 years of laboratory and large-scale tests on the dust filtration process and the basic filtration parameters that determine performance. Physical parameters describing fabric and dust cake structure were defined and three basic dust filtration mechanisms w...

  11. Abnormal human sex chromosome constitutions

    SciTech Connect

    1993-12-31

    Chapter 22, discusses abnormal human sex chromosome constitution. Aneuploidy of X chromosomes with a female phenotype, sex chromosome aneuploidy with a male phenotype, and various abnormalities in X chromosome behavior are described. 31 refs., 2 figs.

  12. Exercises to Improve Gait Abnormalities

    MedlinePlus

    ... Home About iChip Articles Directories Videos Resources Contact Exercises to Improve Gait Abnormalities Home » Article Categories » Exercise and Fitness Font Size: A A A A Exercises to Improve Gait Abnormalities Next Page The manner ...

  13. Filtration Combustion in Smoldering and SHS

    NASA Technical Reports Server (NTRS)

    Matkowsky, Bernard

    1999-01-01

    Smolder waves and SHS (self-propagating high-temperature synthesis) waves are both examples of filtration combustion waves propagating in porous media. Smoldering combustion is important for the study of fire safety. Smoldering itself can cause damage, its products are toxic and it can also lead to the more dangerous gas phase combustion which corresponds to faster propagation at higher temperatures. In SHS, a porous solid sample, consisting of a finely ground powder mixture of reactants, is ignited at one end. A high temperature thermal wave, having a frontal structure, then propagates through the sample converting reactants to products. The SHS technology appears to enjoy a number of advantages over the conventional technology, in which the sample is placed in a furnace and "baked" until it is "well done". The advantages include shorter synthesis times, greater economy, in that the internal energy of the reactions is employed rather than the costly external energy of the furnace, purer products, simpler equipment and no intrinsic limitation on the size of the sample to be synthesized, as exists in the conventional technology. When delivery of reactants through the pores to the reaction site is an important aspect of the combustion process, it is referred to as filtration combustion. The two types of filtration combustion have a similar mathematical formulation, describing the ignition, propagation and extinction of combustion waves in porous media. The goal in each case, however, is different. In smoldering the desired goal is to prevent propagation, whereas in SHS the goal is to insure propagation of the combustion wave, leading to the synthesis of desired products. In addition, the scales in the two areas of application differ. Smoldering generally occurs at lower temperatures and propagation velocities than in SHS. Nevertheless, the two applications have much in common, so that what is learned in one application can be used to advantage in the other. We have

  14. Cellular proliferation after experimental glaucoma filtration surgery

    SciTech Connect

    Jampel, H.D.; McGuigan, L.J.; Dunkelberger, G.R.; L'Hernault, N.L.; Quigley, H.A.

    1988-01-01

    We used light microscopic autoradiography to determine the time course of cellular incorporation of tritiated thymidine (a correlate of cell division) following glaucoma filtration surgery in seven eyes of four cynomolgus monkeys with experimental glaucoma. Incorporation of tritiated thymidine was detected as early as 24 hours postoperatively. Peak incorporation occurred five days postoperatively and had returned to baseline levels by day 11. Cells incorporating tritiated thymidine included keratocytes, episcleral cells, corneal and capillary endothelial cells, and conjunctival and corneal epithelial cells. Transmission electron microscopy was correlated with the autoradiographic results to demonstrate that fibroblasts were dividing on the corneoscleral margin. These findings have potential clinical implications for the use of antiproliferative agents after filtration surgery.

  15. Diatomite releases silica during spirit filtration.

    PubMed

    Gómez, J; Gil, M L A; de la Rosa-Fox, N; Alguacil, M

    2014-09-15

    The purpose of this study was to ascertain whether diatomite is an inert filter aid during spirit filtration. Surely, any compound with a negative effect on the spirit composition or the consumer's health could be dissolved. In this study different diatomites were treated with 36% vol. ethanol/water mixtures and the amounts and structures of the extracted compounds were determined. Furthermore, Brandy de Jerez was diatomite- and membrane-filtered at different temperatures and the silicon content was analysed. It was found that up to 0.36% by weight of diatomite dissolved in the aqueous ethanol and amorphous silica, in the form of hollow spherical microparticles, was the most abundant component. Silicon concentrations in Brandy de Jerez increased by up to 163.0% after contact with diatomite and these changes were more marked for calcined diatomite. In contrast, reductions of more than 30% in silicon concentrations were achieved after membrane filtration at low temperatures. PMID:24767070

  16. Ultrasonic filtration of industrial chemical solutions

    NASA Technical Reports Server (NTRS)

    Cosma, T.

    1974-01-01

    The practical results obtained as a result of filtering industrial chemical solutions under continuous flow conditions with the aid of an ultrasonic filter are presented. The main part of the assembly consists of an ultrasonic generator with an output power of about 400 W and the filtration assembly, in which there is a magnetostrictive amplifier constructed for 20.5 kHz. In addition to ensuring a continuous flow of filtered solution, ultrasonic filters can be replaced or cleaned at intervals of time that are 8-10 times greater than in the case of mechanical filters. They yield considerably better results as far as the size of the filtered particles is concerned. The parameters on which filtration quality depends are also presented.

  17. Optimal filtration of the atmospheric parameters profiles

    NASA Technical Reports Server (NTRS)

    Zuev, V. E.; Glazov, G. N.; Igonin, G. M.

    1986-01-01

    The idea of optimal Marcovian filtration of fluctuating profiles from lidar signals is developed but as applied to a double-frequency sounding which allows the use of large cross sections of elastic scattering and correct separation of the contributions due to aerosol and Rayleigh scatterings from the total lidar return. The filtration efficiency is shown under different conditions of sounding using a computer model. The accuracy of restituted profiles (temperature, pressure, density) is determined by the elements of a posteriori matrix K. The results obtained allow the determination of the lidar power required for providing the necessary accuracy of restitution of the atmospheric parameter profiles at chosen wavelengths of sounding in the ultraviolet and visible range.

  18. Spirometric abnormalities among welders

    SciTech Connect

    Rastogi, S.K.; Gupta, B.N.; Husain, T.; Mathur, N.; Srivastava, S. )

    1991-10-01

    A group of manual welders age group 13-60 years having a mean exposure period of 12.4 {plus minus} 1.12 years were subjected to spirometry to evaluate the prevalence of spirometric abnormalities. The welders showed a significantly higher prevalence of respiratory impairment than that observed among the unexposed controls as a result of exposure to welding gases which comprised fine particles of lead, zinc, chromium, and manganese. This occurred despite the lower concentration of the pollutants at the work place. In the expose group, the smoking welders showed a prevalence of respiratory impairment significantly higher than that observed in the nonsmoking welders. The results of the pulmonary function tests showed a predominantly restrictive type of pulmonary impairment followed by a mixed ventilatory defect among the welders. The effect of age on pulmonary impairment was not discernible. Welders exposed for over 10 years showed a prevalence of respiratory abnormalities significantly higher than those exposed for less than 10 years. Smoking also had a contributory role.

  19. Short- and long-term follow-up of glomerular and tubular renal markers of kidney function in hyperthyroid cats after treatment with radioiodine.

    PubMed

    van Hoek, I; Lefebvre, H P; Peremans, K; Meyer, E; Croubels, S; Vandermeulen, E; Kooistra, H; Saunders, J H; Binst, D; Daminet, S

    2009-01-01

    Hyperthyroidism can mask co-existing chronic kidney disease (CKD). Previous studies showed that post-treatment renal azotemia can be predicted by pre-treatment assessment of glomerular filtration rate (GFR). We hypothesized that treatment of hyperthyroidism may have different effects on glomerular and tubular function and these changes might be predicted by additional pre-treatment variables than GFR. Serum total T4 (TT4), creatinine and blood urea nitrogen (BUN), blood pressure (BP), body weight (BW), GFR, urine specific gravity (USG), urinary protein/creatinine ratio (UPC) and retinol binding protein/creatinine ratio (uRBP/c) were evaluated before and 1, 4, 12 and 24 weeks post-treatment with radioiodine ((131)I) in 21 non-azotemic hyperthyroid cats. Cats were divided 24 weeks post-treatment into group A (normal kidney function, n=16) and group B (impaired kidney function, n=5). Serum TT4, GFR, UPC and uRBP/c decreased significantly after treatment for the complete group and group A (P<0.05), although GFR and uRBP/c did not change in group B. Serum creatinine and BW increased significantly from 1 week after treatment (P<0.05). There was no change in BUN, USG or BP. Pre-treatment serum TT4, GFR and USG differed significantly between group A and B (P<0.05). GFR at 4 weeks after treatment and maximum decrease in GFR could be partially predicted by a formula using pre-treatment GFR, serum TT4, serum creatinine, BUN and/or USG. Significant changes in kidney function occur within 4 weeks post-treatment and none thereafter. Pre-treatment measurement of GFR, USG and serum TT4 can have possible predictive value regarding the development of post-treatment renal azotemia. PMID:19010632

  20. ER stress and basement membrane defects combine to cause glomerular and tubular renal disease resulting from Col4a1 mutations in mice

    PubMed Central

    Jones, Frances E.; Bailey, Matthew A.; Murray, Lydia S.; Lu, Yinhui; McNeilly, Sarah; Schlötzer-Schrehardt, Ursula; Lennon, Rachel; Sado, Yoshikazu; Brownstein, David G.; Mullins, John J.; Kadler, Karl E.; Van Agtmael, Tom

    2016-01-01

    ABSTRACT Collagen IV is a major component of basement membranes, and mutations in COL4A1, which encodes collagen IV alpha chain 1, cause a multisystemic disease encompassing cerebrovascular, eye and kidney defects. However, COL4A1 renal disease remains poorly characterized and its pathomolecular mechanisms are unknown. We show that Col4a1 mutations in mice cause hypotension and renal disease, including proteinuria and defects in Bowman's capsule and the glomerular basement membrane, indicating a role for Col4a1 in glomerular filtration. Impaired sodium reabsorption in the loop of Henle and distal nephron despite elevated aldosterone levels indicates that tubular defects contribute to the hypotension, highlighting a novel role for the basement membrane in vascular homeostasis by modulation of the tubular response to aldosterone. Col4a1 mutations also cause diabetes insipidus, whereby the tubular defects lead to polyuria associated with medullary atrophy and a subsequent reduction in the ability to upregulate aquaporin 2 and concentrate urine. Moreover, haematuria, haemorrhage and vascular basement membrane defects confirm an important vascular component. Interestingly, although structural and compositional basement membrane defects occurred in the glomerulus and Bowman's capsule, no tubular basement membrane defects were detected. By contrast, medullary atrophy was associated with chronic ER stress, providing evidence for cell-type-dependent molecular mechanisms of Col4a1 mutations. These data show that both basement membrane defects and ER stress contribute to Col4a1 renal disease, which has important implications for the development of treatment strategies for collagenopathies. PMID:26839400

  1. The role of cell-extracellular matrix interactions in glomerular injury.

    PubMed

    Borza, Corina M; Pozzi, Ambra

    2012-05-15

    Glomerulosclerosis is characterized by excessive deposition of extracellular matrix within the glomeruli of the kidney, glomerular cell death, and subsequent loss of functional glomeruli. While in physiological situations the levels of extracellular matrix components are kept constant by a tight balance between formation and degradation, in the case of injury that results in fibrosis there is increased matrix deposition relative to its breakdown. Multiple factors control matrix synthesis and degradation, thus contributing to the development of glomerulosclerosis. This review focuses primarily on the role of cell-matrix interactions, which play a critical role in governing glomerular cell cues in both healthy and diseased kidneys. Cell-extracellular matrix interactions are made possible by various cellular receptors including integrins, discoidin domain receptors, and dystroglycan. Upon binding to a selective extracellular matrix protein, these receptors activate intracellular signaling pathways that can either downregulate or upregulate matrix synthesis and deposition. This, together with the observation that changes in the expression levels of matrix receptors have been documented in glomerular disease, clearly emphasizes the contribution of cell-matrix interactions in glomerular injury. Understanding the molecular mechanisms whereby extracellular matrix receptors regulate matrix homeostasis in the course of glomerular injury is therefore critical for devising more effective therapies to treat and ideally prevent glomerulosclerosis. PMID:22417893

  2. THE ROLE OF CELL-EXTRACELLULAR MATRIX INTERACTIONS IN GLOMERULAR INJURY

    PubMed Central

    Borza, Corina M.; Pozzi, Ambra

    2013-01-01

    Glomerulosclerosis is characterized by excessive deposition of extracellular matrix within the glomeruli of the kidney, glomerular cell death, and subsequent loss of functional glomeruli. While in physiological situations the levels of extracellular matrix components are kept constant by a tight balance between formation and degradation, in the case of injury that results in fibrosis there is increased matrix deposition relative to its breakdown. Multiple factors control matrix synthesis and degradation, thus contributing to the development of glomerulosclerosis. This review focuses primarily on the role of cell-matrix interactions, which play a critical role in governing glomerular cell cues in both healthy and diseased kidneys. Cell-extracellular matrix interactions are made possible by various cellular receptors including integrins, discoidin domain receptors, and dystroglycan. Upon binding to a selective extracellular matrix protein, these receptors activate intracellular signaling pathways that can either downregulate or upregulate matrix synthesis and deposition. This, together with the observation that changes in the expression levels of matrix receptors have been documented in glomerular disease, clearly emphasizes the contribution of cell-matrix interactions in glomerular injury. Understanding the molecular mechanisms whereby extracellular matrix receptors regulate matrix homeostasis in the course of glomerular injury is therefore critical for devising more effective therapies to treat and ideally prevent glomerulosclerosis. PMID:22417893

  3. Glomerular alterations in uranyl acetate-induced acute renal failure in rabbits

    SciTech Connect

    Kobayashi, S.; Nagase, M.; Honda, N.; Hishida, A.

    1984-12-01

    The study was performed to elucidate the progression and regression of superficial and inner glomerular alterations in uranyl acetate-induced renal failure in rabbits. Fifteen hours after the drug injection, creatinine clearance (CCr) decreased to 55% of controls with slightly elevated plasma creatinine concentration (initiation stage). After 5 days, urine flow and CCr decreased to approximately zero, with severe azotemia (maintenance stage). Scanning electron microscopic observations in these stages revealed a flattening and spreading of podocyte cell bodies associated with loss of epithelial foot processes, and reduction in the density of endothelial fenestrae. These changes were more advanced in the maintenance stage. Glomerular and fenestral diameters did not significantly change in the initiation stage but increased in the maintenance stage. There was no significant difference in these morphologic alterations, however, between the superficial and inner glomeruli. Glomerular alterations reverted to normal within 14 days, with good recovery of glomerular function. The findings show no significant difference in the progression or regression of the glomerular changes between the superficial and deep cortex. These morphologic changes may play a role in the reduction of CCr observed in this model.

  4. Distinct pathogenic effects of group B coxsackieviruses on human glomerular and tubular kidney cells.

    PubMed Central

    Conaldi, P G; Biancone, L; Bottelli, A; De Martino, A; Camussi, G; Toniolo, A

    1997-01-01

    The six group B coxsackieviruses (CVBs) are highly prevalent human pathogens that cause viremia followed by involvement of different organs. Clinical and experimental evidence suggests that CVBs can induce kidney injury, but the susceptibility of human renal cells to these viruses is unknown. By using pure cultures of human glomerular and tubular cells, we demonstrated that all CVBs are capable of productively infecting renal cells of three different histotypes. Distinct pathogenic effects were observed. Proximal tubular epithelial cells and, to a lesser extent, glomerular podocytes were highly susceptible to CVBs; in both cases, infection led to cytolysis. In contrast, glomerular mesangial cells supported the replication of the six CVBs but failed to develop overt cytopathologic changes. Mesangial cells continued to produce infectious progeny for numerous serial subcultures (i.e., more than 50 days), especially with type 1, 3, 4, and 5 viruses. In the above cells, persistent infection induced the de novo synthesis of platelet-derived growth factor A/B and enhanced the release of transforming growth factor beta1/2. These two factors are important mediators of progression from glomerular inflammation to glomerulosclerosis. CVB replication appeared also to impair the phagocytic and contractile activity of mesangial cells. Loss of these properties--which are important in glomerular physiopathology--may contribute to the development of progressive nephropathy. The results show that CVBs induce distinct effects in different types of cultured renal cells and suggest that CVB infections may be associated with both acute and progressive renal injury. PMID:9371576

  5. Converting enzyme inhibition and the glomerular hemodynamic response to glycine in diabetic rats.

    PubMed

    Slomowitz, L A; Peterson, O W; Thomson, S C

    1999-07-01

    GFR normally increases during glycine infusion. This response is absent in humans and rats with established diabetes mellitus. In diabetic patients, angiotensin-converting enzyme inhibition (ACEI) restores the effect of glycine on GFR. To ascertain the glomerular hemodynamic basis for this effect of ACEI, micropuncture studies were performed in male Wistar-Froemter rats after 5 to 6 wk of insulin-treated streptozotocin diabetes. The determinants of single-nephron GFR (SNGFR) were assessed in each rat before and during glycine infusion. Studies were performed in diabetics, diabetics after 5 d of ACEI (enalapril in the drinking water), and weight-matched controls. Diabetic rats manifest renal hypertrophy and glomerular hyperfiltration but not glomerular capillary hypertension. ACEI reduced glomerular capillary pressure, increased glomerular ultrafiltration coefficient, and did not mitigate hyperfiltration. In controls, glycine increased SNGFR by 30% due to increased nephron plasma flow. In diabetics, glycine had no effect on any determinant of SNGFR. In ACEI-treated diabetics, the SNGFR response to glycine was indistinguishable from nondiabetics, but the effect of glycine was mediated by greater ultrafiltration pressure rather than by greater plasma flow. These findings demonstrate that: (1) The absent response to glycine in established diabetes does not indicate that renal functional reserve is exhausted by hyperfiltration; and (2) ACEI restores the GFR response to glycine in established diabetes, but this response is mediated by increased ultrafiltration pressure rather than by increased nephron plasma flow. PMID:10405200

  6. Glomerular ultrastructure of the trout, Salmo gairdneri: effects of angiotensin II and adaptation to seawater.

    PubMed

    Gray, C J; Brown, J A

    1987-08-01

    The effect of angiotensin infusion on the glomerular ultrastructure of freshwater- and seawater-adapted rainbow trout. Salmo gairdneri, has been examined by scanning and transmission electron microscopy. Adaptation of trout to seawater resulted in epithelial podocyte flattening, primary process broadening and apparent loss of foot processes in almost all glomeruli, features which were uncommon in freshwater-adapted trout. Similar changes were induced by infusion of freshwater-adapted animals with angiotensin, suggesting that the renin-angiotensin system plays a role in the modification of glomerular epithelial ultrastructure. Adaptation of trout to seawater also reduced glomerular diameter, but infusion of freshwater-adapted animals with angiotensin did not mirror this effect. Infusion of angiotensin into seawater-adapted animals increased the overall thickness of glomerular basement membrane by increasing the lamina rara interna and lamina densa. This did not occur when freshwater-adapted fish were either infused with angiotensin or adapted to seawater. These findings suggest that other humoral systems are involved in the control of glomerular diameter and basement membrane thickness as part of an integrated response to increased environmental salinity. PMID:3621307

  7. GEC-targeted HO-1 expression reduces proteinuria in glomerular immune injury.

    PubMed

    Duann, Pu; Lianos, Elias A

    2009-09-01

    Induction of heme oxygenase (HO)-1 is a key defense mechanism against oxidative stress. Compared with tubules, glomeruli are refractory to HO-1 upregulation in response to injury. This can be a disadvantage as it may be associated with insufficient production of cytoprotective heme-degradation metabolites. We, therefore, explored whether 1) targeted HO-1 expression can be achieved in glomeruli without altering their physiological integrity and 2) this expression reduces proteinuria in immune injury induced by an anti-glomerular basement membrane (GBM) antibody (Ab). We employed a 4.125-kb fragment of a mouse nephrin promoter downstream to which a FLAG-tagged hHO-1 cDNA sequence was inserted and subsequently generated transgenic mice from the FVB/N parental strain. There was a 16-fold higher transgene expression in the kidney than nonspecific background (liver) while the transprotein immunolocalized in glomerular epithelial cells (GEC). There was no change in urinary protein excretion, indicating that GEC-targeted HO-1 expression had no effect on glomerular protein permeability. Urinary protein excretion in transgenic mice with anti-GBM Ab injury (days 3 and 6) was significantly lower compared with wild-type controls. There was no significant change in renal expression levels of profibrotic (TGF-beta1) or anti-inflammatory (IL-10) cytokines in transgenic mice with anti-GBM Ab injury. These observations indicate that GEC-targeted HO-1 expression does not alter glomerular physiological integrity and reduces proteinuria in glomerular immune injury. PMID:19587144

  8. Tailoring wall permeabilities for enhanced filtration

    NASA Astrophysics Data System (ADS)

    Herterich, J. G.; Vella, D.; Field, R. W.; Hankins, N. P.; Griffiths, I. M.

    2015-05-01

    The build-up of contaminants at the wall of cross-flow membrane filtration systems can be detrimental to the operation of such systems because of, amongst other things, the osmotic backflow it may induce. In this paper, we propose a strategy to avoid the negative effects of backflow due to osmosis by using 2D channels bounded by walls with a combination of permeable and impermeable segments. We show that preventing flow through the final portion of the channel can increase the efficiency of filtration and we determine the optimal fraction occupied by the permeable wall that maximizes efficiency. Our analysis uses a combination of numerical techniques and asymptotic analysis in the limit of low wall permeabilities. Finally, we consider how the energy cost of filtration depends on the Péclet number and show that the energy cost per unit of filtered water may be minimized by appropriately choosing both the Péclet number and the permeable-region fraction.

  9. Evaluation of natural coagulants for direct filtration.

    PubMed

    Mandloi, M; Chaudhari, S; Folkard, G K

    2004-04-01

    In the present study surjana (Moringa oleifera) seed, maize (Zea mays) and chitosan were used in direct filtration of Bilaoli lake water and evaluated for their efficiency in removing turbidity and microorganisms from water. The experiments with these natural coagulants gave filtered water turbidity less than or almost equal to 1NTU and thereby met the turbidity criteria for drinking water as per WHO guidelines. Bilaoli lake water had low ionic strength and low turbidity which represents one of the most difficult raw waters to treat, but natural coagulants in direct filtration achieved good filtrate quality. The head loss development across the filter bed with chitosan was more than that of alum, while with maize it was comparable to that of alum. With M. oleifera seeds the head loss was much less in comparison to alum. The average most probable number (MPN) reductions obtained with M. oleifera seeds, maize and chitosan were 97.35%, 95.4% and 87.1% respectively, whereas, with alum it was only 7.7%. PMID:15214453

  10. Microvascular filtration in subjects with connective tissue disorders.

    PubMed Central

    Edwards, J C; Snaith, M L

    1984-01-01

    A simple non-invasive method for studying microvascular filtration in the non-articular tissues of the forearm is described. Rates of filtration under a standard hydrostatic pressure were measured in 20 normal female subjects and 44 female subjects with connective tissue disorders. An increased mean filtration rate was found in 14 subjects with rheumatoid arthritis. In 20 subjects with systemic lupus erythematosus and 10 subjects with scleroderma no such generalised increase in filtration rates was seen, but isolated cases had very high filtration rates, suggesting a more heterogeneous physiological disturbance. Increased filtration was not associated with the presence of oedema. This confirms doubts raised by other workers about the importance of filtration in the genesis of clinical oedema. Images PMID:6476914

  11. Filtration Combustion in Smoldering and SHS

    NASA Technical Reports Server (NTRS)

    Matkowsky, Bernard J.

    2001-01-01

    Smolder waves and SHS (self-propagating high-temperature synthesis) waves are both examples of filtration combustion waves propagating in porous media. Smoldering combustion is important for the study of fire safety. Smoldering itself can cause damage, its products are toxic and it can also lead to the more dangerous gas phase combustion which corresponds to faster propagation at higher temperatures. In SHS , a porous solid sample, consisting of a finely ground powder mixture of reactants, is ignited at one end. A high temperature thermal wave, having a frontal structure, then propagates through the sample converting reactants to products. The SHS technology appears to enjoy a number of advantages over the conventional technology, in which the sample is placed in a furnace and "baked" until it is "well done". The advantages include shorter synthesis times, greater economy, in that the internal energy of the reactions is employed rather than the costly external energy of the furnace, purer products, simpler equipment and no intrinsic limitation on the size of the sample to be synthesized as exists in the conventional technology. When delivery of reactants through the pores to the reaction site is an important aspect of the combustion process, it is referred to as filtration combustion. The two types of filtration combustion have a similar mathematical formulation, describing the ignition, propagation and extinction of combustion waves in porous media. The goal in each case, however, is different. In smoldering the desired goal is to prevent propagation, whereas in SHS the goal is to ensure propagation of the combustion wave, leading to the synthesis of desired products. In addition, the scales in the two areas of application differ. Smoldering generally occurs at lower temperatures and propagation velocities than in SHS nevertheless, the two applications have much in common so that what is learned fit make application can be used to advantage in the other. In porous

  12. Eye movement abnormalities.

    PubMed

    Moncayo, Jorge; Bogousslavsky, Julien

    2012-01-01

    Generation and control of eye movements requires the participation of the cortex, basal ganglia, cerebellum and brainstem. The signals of this complex neural network finally converge on the ocular motoneurons of the brainstem. Infarct or hemorrhage at any level of the oculomotor system (though more frequent in the brain-stem) may give rise to a broad spectrum of eye movement abnormalities (EMAs). Consequently, neurologists and particularly stroke neurologists are routinely confronted with EMAs, some of which may be overlooked in the acute stroke setting and others that, when recognized, may have a high localizing value. The most complex EMAs are due to midbrain stroke. Horizontal gaze disorders, some of them manifesting unusual patterns, may occur in pontine stroke. Distinct varieties of nystagmus occur in cerebellar and medullary stroke. This review summarizes the most representative EMAs from the supratentorial level to the brainstem. PMID:22377853

  13. Odorant response properties of individual neurons in an olfactory glomerular module

    PubMed Central

    Kikuta, Shu; Fletcher, Max L.; Homma, Ryota; Yamasoba, Tatsuya; Nagayama, Shin

    2013-01-01

    Summary Neuronal networks that are directly associated with glomeruli in the olfactory bulb are thought to comprise functional modules. However, this has not yet been experimentally proven. In this study, we explored the anatomical and functional architecture of glomerular modules using in vivo two-photon calcium imaging. Surprisingly, the deep portions of the glomerular modules showed considerable spatial overlap with other modules. Juxtaglomerular cells showed similar excitatory odorant response profiles to presynaptic olfactory sensory neuron inputs. Mitral cells exhibited a more sharply tuned molecular receptive range compared to juxtaglomerular cells, and their odorant response profiles varied depending on their interneuronal horizontal distances. These data suggest that glomerular modules are composed of functionally distinct neurons, and that homogenous odor inputs to each glomerulus may be parsed and processed in different fashions within the modules before being sent to higher olfactory centers. PMID:23522047

  14. Glomerular deposition of immune complexes in dogs following natural infection with canine adenovirus.

    PubMed

    Morrison, W I; Nash, A S; Wright, N G

    1975-06-14

    The renal lesions were studied in eight dogs which had either died as a result of acute canine adenovirus infection (Rubarth's disease) or were in various stages of recovery from the clinical disease. Using immunofluorescence techniques granular deposits of IgG were detected in the glomeruli of six dogs; four of these animals had similar glomerular deposits of canine adenovirus antigen. Eluates obtained from kidney tissue of four dogs were found to contain antiviral antibody. Histologically those animals in which glomerular deposits of IgG and viral antigen were detected showed segmental glomerular hypercellularity. These findings were attributed to the deposition of circulating virus antigen-antibody complexes in the glomeruli. PMID:166480

  15. Characterization of Filtration Scale-Up Performance

    SciTech Connect

    Daniel, Richard C.; Billing, Justin M.; Luna, Maria L.; Cantrell, Kirk J.; Peterson, Reid A.; Bonebrake, Michael L.; Shimskey, Rick W.; Jagoda, Lynette K.

    2009-03-09

    The scale-up performance of sintered stainless steel crossflow filter elements planned for use at the Pretreatment Engineering Platform (PEP) and at the Waste Treatment and Immobilization Plant (WTP) were characterized in partial fulfillment (see Table S.1) of the requirements of Test Plan TP RPP WTP 509. This test report details the results of experimental activities related only to filter scale-up characterization. These tests were performed under the Simulant Testing Program supporting Phase 1 of the demonstration of the pretreatment leaching processes at PEP. Pacific Northwest National Laboratory (PNNL) conducted the tests discussed herein for Bechtel National, Inc. (BNI) to address the data needs of Test Specification 24590-WTP-TSP-RT-07-004. Scale-up characterization tests employ high-level waste (HLW) simulants developed under the Test Plan TP-RPP-WTP-469. The experimental activities outlined in TP-RPP-WTP-509 examined specific processes from two broad areas of simulant behavior: 1) leaching performance of the boehmite simulant as a function of suspending phase chemistry and 2) filtration performance of the blended simulant with respect to filter scale-up and fouling. With regard to leaching behavior, the effect of anions on the kinetics of boehmite leaching was examined. Two experiments were conducted: 1) one examined the effect of the aluminate anion on the rate of boehmite dissolution and 2) another determined the effect of secondary anions typical of Hanford tank wastes on the rate of boehmite dissolution. Both experiments provide insight into how compositional variations in the suspending phase impact the effectiveness of the leaching processes. In addition, the aluminate anion studies provide information on the consequences of gibbsite in waste. The latter derives from the expected fast dissolution of gibbsite relative to boehmite. This test report concerns only results of the filtration performance with respect to scale-up. Test results for boehmite

  16. Removal of pathogens using riverbank filtration

    NASA Astrophysics Data System (ADS)

    Cote, M. M.; Emelko, M. B.; Thomson, N. R.

    2003-04-01

    Although more than hundred years old, in situ or Riverbank Filtration (RBF) has undergone a renewed interest in North America because of its potential as a surface water pre-treatment tool for removal of pathogenic microorganisms. A new RBF research field site has been constructed along the banks of the Grand River in Kitchener, Ontario, Canada to assess factors influencing pathogen removal in the subsurface. Implementation of RBF and appropriate design of subsequent treatment (UV, chlorination, etc.) processes requires successful quantification of in situ removals of Cryptosporidium parvum or a reliable surrogate parameter. C.~parvum is often present in surface water at low indigenous concentrations and can be difficult to detect in well effluents. Since releases of inactivated C.~parvum at concentrations high enough for detection in well effluents are cost prohibitive, other approaches for demonstrating effective in situ filtration of C.~parvum must be considered; these include the use of other microbial species or microspheres as indicators of C.~parvum transport in the environment. Spores of Bacillus subtilis may be considered reasonable indicators of C.~parvum removal by in situ filtration because of their size (˜1 μm in diameter), spherical shape, relatively high indigenous concentration is many surface waters, and relative ease of enumeration. Based on conventional particle filtration theory and assuming equivalent chemical interactions for all particle sizes, a 1 μm B.~subtilis spore will be removed less readily than a larger C. parvum oocyst (4-6 μm) in an ideal granular filter. Preliminary full-scale data obtained from a high rate RBF production well near the new RBF test site demonstrated greater than 1 log removal of B.~subtilis spores. This observed spore removal is higher than that prescribed by the proposed U.S. Long Term 2 Enhanced Surface Water Treatment Rule for C.~parvum. To further investigate the removal relationship between C

  17. Changes in glomerular hemodynamic response to angiotensin II after subacute renal denervation in rats.

    PubMed Central

    Tucker, B J; Mundy, C A; Maciejewski, A R; Printz, M P; Ziegler, M G; Pelayo, J C; Blantz, R C

    1986-01-01

    We examined the changes in glomerular hemodynamics produced by angiotensin II (AII) in both normal Munich-Wistar rats and rats which were unilaterally renal denervated (measured kidney) 4-6 d prior to the measurement periods. Measurements of glomerular dynamics were performed in a control period after plasma volume expansion and during infusion of 11 ng X 100 g body wt-1 X min-1 of AII. The glomerular hydrostatic pressure gradient increased from 38 +/- 1 to 49 +/- 1 mmHg in denervated rats compared with a lesser response in controls (from 39 +/- 1 to 45 +/- 1 mmHg, P less than 0.05). Single nephron plasma flow decreased from 213 +/- 17 to 87 +/- 4 nl X min-1 X g kidney wt (KW)-1 in denervated kidneys versus a more modest decrease in control kidneys (from 161 +/- 9 to 102 +/- 5 nl X min X gKW-1). These changes were due to a greater increase in both afferent and efferent arteriolar resistance after AII infusion in denervated compared with control kidneys. Glomerular AII receptor maximum binding was 1,196 +/- 267 fmol/mg protein in denervated kidneys compared with 612 +/- 89 fmol/mg protein (P less than 0.01) in controls with no change in receptor affinity. We conclude the subacute unilateral renal denervation results in renal vasodilation, denervation magnifies the vasoconstrictive effect of AII infusion on glomerular hemodynamics, and the observed increased response to AII after denervation is associated with increases in glomerular AII receptors. PMID:3745432

  18. Cells of renin lineage are adult pluripotent progenitors in experimental glomerular disease

    PubMed Central

    Kaverina, Natalya V.; Eng, Diana G.; Krofft, Ronald D.; Glenn, Sean T.; Duffield, Jeremy S.; Gross, Kenneth W.; Shankland, Stuart J.

    2015-01-01

    Modified vascular smooth muscle cells of the kidney afferent arterioles have recently been shown to serve as progenitors for glomerular epithelial cells in response to glomerular injury. To determine whether such cells of renin lineage (CoRL) serve as progenitors for other cells in kidney disease characterized by both glomerular and tubulointerstitial injury, permanent genetic cell fate mapping of adult CoRL using Ren1cCreER × Rs-tdTomato-R reporter mice was performed. TdTomato-labeled CoRL were almost completely restricted to the juxtaglomerular compartment in healthy kidneys. Following 2 wk of antibody-mediated focal segmental glomerulosclerosis (FSGS) or 16 wk of ⅚ nephrectomy-induced chronic kidney diseases, tdTomato-mapped CoRL were identified in both interstitial and glomerular compartments. In the interstitium, PDGFβ receptor (R)-expressing cells significantly increased, and a portion of these expressed tdTomato. This was accompanied by a decrease in native pericyte number, but an increase in the number of tdTomato cells that coexpressed the pericyte markers PDGFβ-R and NG2. These cells surrounded vessels and coexpressed the pericyte markers CD73 and CD146, but not the endothelial marker ERG. Within glomeruli of reporter mice with the ⅚ nephrectomy model, a subset of labeled CoRL migrated to the glomerular tuft and coexpressed podocin and synaptopodin. By contrast, labeled CoRL were not detected in glomerular or interstitial compartments following uninephrectomy. These observations indicate that in addition to supplying new adult podocytes to glomeruli, CoRL have the capacity to become new adult pericytes in the setting of interstitial disease. We conclude that CoRL have the potential to function as progenitors for multiple adult cell types in kidney disease. PMID:26062877

  19. Cells of renin lineage are adult pluripotent progenitors in experimental glomerular disease.

    PubMed

    Pippin, Jeffrey W; Kaverina, Natalya V; Eng, Diana G; Krofft, Ronald D; Glenn, Sean T; Duffield, Jeremy S; Gross, Kenneth W; Shankland, Stuart J

    2015-08-15

    Modified vascular smooth muscle cells of the kidney afferent arterioles have recently been shown to serve as progenitors for glomerular epithelial cells in response to glomerular injury. To determine whether such cells of renin lineage (CoRL) serve as progenitors for other cells in kidney disease characterized by both glomerular and tubulointerstitial injury, permanent genetic cell fate mapping of adult CoRL using Ren1cCreER × Rs-tdTomato-R reporter mice was performed. TdTomato-labeled CoRL were almost completely restricted to the juxtaglomerular compartment in healthy kidneys. Following 2 wk of antibody-mediated focal segmental glomerulosclerosis (FSGS) or 16 wk of ⅚ nephrectomy-induced chronic kidney diseases, tdTomato-mapped CoRL were identified in both interstitial and glomerular compartments. In the interstitium, PDGFβ receptor (R)-expressing cells significantly increased, and a portion of these expressed tdTomato. This was accompanied by a decrease in native pericyte number, but an increase in the number of tdTomato cells that coexpressed the pericyte markers PDGFβ-R and NG2. These cells surrounded vessels and coexpressed the pericyte markers CD73 and CD146, but not the endothelial marker ERG. Within glomeruli of reporter mice with the ⅚ nephrectomy model, a subset of labeled CoRL migrated to the glomerular tuft and coexpressed podocin and synaptopodin. By contrast, labeled CoRL were not detected in glomerular or interstitial compartments following uninephrectomy. These observations indicate that in addition to supplying new adult podocytes to glomeruli, CoRL have the capacity to become new adult pericytes in the setting of interstitial disease. We conclude that CoRL have the potential to function as progenitors for multiple adult cell types in kidney disease. PMID:26062877

  20. Dibutyryl cyclic AMP does not influence glomerular collagen or basement membrane production in vitro.

    PubMed

    Uw, V Y; Cohen, M P

    1980-02-01

    Glomeruli isolated from normal rat renal cortex were incubated for 3 hr with radiolabeled proline in the presence or absence of dibutyryl cyclic AMP. Following incubation, glomerular basement membranes were purified with osmotic lysis followed by selective solubilization of the cell membranes and intracellular proteins with detergents. This technique permitted quantitative recovery of radiolabeled membranes synthesized under different incubational conditions. Dibutyryl cyclic AMP did not affect the incorporation of radioactive precursor glomerular basement membrane (control = 14.72 +/- 1.08 cpm/microgram of membrane protein; cyclic AMP = 14.43 +/- 1.13). Nondialyzable [14C]protein and hydroxy[14C]proline were also measured in the media and in the various glomerular cell fractions obtained during isolation of the basement membranes. Protein ([14C]proline) and collagen (OH[14C]proline) secretion into the media in incubations with cyclic AMP did not differ from that in control incubations. OH[14C]proline content was greatest (congruent to 23% in the water-soluble fraction recovered after osmotic lysis, but significant amounts of OH[14C]proline were also associated with the detergent-solubilized cell fractions. Dibutyryl cyclic AMP had no effect on either glomerular protein or collagen synthesis in these experiments. The results suggest that total glomerular basement membrane production in mixed cell populations is not modulated via a cyclic AMP--coordinated mechanism but do not exclude the possibility that cyclic AMP modulates the amount or kind of collagen synthesis by individual glomerular cell types. PMID:6243687

  1. The Tetraspanin CD37 Protects Against Glomerular IgA Deposition and Renal Pathology

    PubMed Central

    Rops, Angelique L.; Figdor, Carl G.; van der Schaaf, Alie; Tamboer, Wim P.; Bakker, Marinka A.; Berden, Jo H.; Dijkman, Henry B.P.M.; Steenbergen, Eric J.; van der Vlag, Johan; van Spriel, Annemiek B.

    2010-01-01

    The tetraspanin protein CD37 is a leukocyte-specific transmembrane protein that is highly expressed on B cells. CD37-deficient (CD37−/−) mice exhibit a 15-fold increased level of immunoglobulin A (IgA) in serum and elevated numbers of IgA+ plasma cells in lymphoid organs. Here, we report that CD37−/− mice spontaneously develop renal pathology with characteristics of human IgA nephropathy. In young naïve CD37−/− mice, mild IgA deposition in glomeruli was observed. However, CD37−/− mice developed high titers of IgA immune complexes in serum during aging, which was associated with increased glomerular IgA deposition. Severe mesangial proliferation, fibrosis, and hyalinosis were apparent in aged CD37−/− mice, whereas albuminuria was mild. To further evaluate the role of CD37 in glomerular disease, we induced anti–glomerular basement membrane (GBM) nephritis in mice. CD37−/− mice developed higher IgA serum levels and glomerular deposits of anti-GBM IgA compared with wild-type mice. Importantly, glomerular macrophage and neutrophil influx was significantly higher in CD37−/− mice during both the heterologous and autologous phase of anti-GBM nephritis. Taken together, tetraspanin CD37 controls the formation of IgA-containing immune complexes and glomerular IgA deposition, which induces influx of inflammatory myeloid cells. Therefore, CD37 may protect against the development of IgA nephropathy. PMID:20348240

  2. Immune adherence in renal glomeruli. Complement receptor sites on glomerular capillary epithelial cells.

    PubMed Central

    Burkholder, P. M.; Oberley, T. D.; Barber, T. A.; Beacom, A.; Koehler, C.

    1977-01-01

    Several very recent reports have indicated the presence of receptor sites for the third component of complement in human but not other vertebrate renal glomeruli. The present study constitutes a demonstration that the glomerular capillary epithelial cell bears this receptor, detectable with either EAC complexes (EAC1423b) or fluores ceinated zymosan-C3 (ZC3b) complexes, Fresh, unfixed frozen sections of normal or diseased human kidneys, mechanically isolated human glomeruli, dissociated glomerular cells, and glomeruli and golmerular cells maintained in tissue culture were examined with various EAC complexes or ZC3b and examined by phase light microscopy, fluorescence microscopy, or transmission and scanning electron microscopy. Clearly, by scanning electron microscopy it was determined that glomerular capillary epithelial cells bind the immune-adherence EAC indicator cells. Because glomeruli or glomerular epithelial cells did not bind E, EA, EACI, EAC14, or EAC142 but did bind EAC1423b or ZC3b, it is concluded that C3b (activated bound fragment of the third component of complement) is responsible for the immune-adherence reaction in glomeruli. Preliminary examination of diseased renal biopsies indicates that sclerotic glomeruli, focal segmental sclerotic or proliferative glomerular capillary lesions, and proliferative epithelial crescents are immune-adherence negative. Furthermore, a clear or consistent inverse relationship between glomerular capillary deposits of C3 which presumably might block epithelial C3 receptor sites, and immune-adherence reactivity with EAC in vitro was not as evident in this study as reported previously by other investigators. Nevertheless, it is still attractive to conceive that glomerular C3 receptor sites might be responsible for binding of antigen-antibody-complement complexes and formation of immune-complex deposits, at least on the epimembranous (subepithelial) surface of glomerular capillary walls. Inability to demonstrate this

  3. Glomerular anionic site distribution in nonproteinuric rats. A computer-assisted morphometric analysis.

    PubMed

    Pilia, P A; Swain, R P; Williams, A V; Loadholt, C B; Ainsworth, S K

    1985-12-01

    The cationic ultrastructural tracer polyethyleneimine (PEI: pI approximately equal to 11.0), binds electrophysically to uniformly spaced discrete electron-dense anionic sites present in the laminae rarae of the rat glomerular basement membrane (GBM), mesangial reflections of the GBM, Bowman's capsule, and tubular basement membranes when administered intravenously. Computer-assisted morphometric analysis of glomerular anionic sites reveals that the maximum concentration of stainable lamina rara externa (lre) sites (21/10,000 A GBM) occurs 60 minutes after PEI injection with a site-site interspacing of 460 A. Lamina rara interna (lri) sites similarly demonstrate a maximum concentration (20/10,000 A GBM) at 60 minutes with a periodicity of 497 A. The concentration and distribution of anionic sites within the lri was irregular in pattern and markedly decreased in number, while the lre possesses an electrical field that is highly regular at all time intervals analyzed (15, 30, 60, 120, 180, 240, and 300 minutes). Immersion and perfusion of renal tissue with PEI reveals additional heavy staining of the epithelial and endothelial cell sialoprotein coatings. PEI appears to bind to glomerular anionic sites reversibly: ie, between 60 and 180 minutes the concentration of stained sites decreases. At 300 minutes, the interspacing once again approaches the 60-minute concentration. This suggests a dynamic turnover or dissociation followed by a reassociation of glomerular negatively charged PEI binding sites. In contrast, morphometric analysis of anionic sites stained with lysozyme and protamine sulfate reveals interspacings of 642 A and 585 A, respectively; in addition, these tracers produce major glomerular ultrastructural alterations and induce transient proteinuria. PEI does not induce proteinuria in rats, nor does it produce glomerular morphologic alterations when ten times the tracer dosage is administered intravenously. These findings indicate that the choice of

  4. Prohibitin-2 Depletion Unravels Extra-Mitochondrial Functions at the Kidney Filtration Barrier.

    PubMed

    Ising, Christina; Bharill, Puneet; Brinkkoetter, Sibylle; Brähler, Sebastian; Schroeter, Christina; Koehler, Sybille; Hagmann, Henning; Merkwirth, Carsten; Höhne, Martin; Müller, Roman U; Fabretti, Francesca; Schermer, Bernhard; Bloch, Wilhelm; Kerjaschki, Dontscho; Kurschat, Christine E; Benzing, Thomas; Brinkkoetter, Paul T

    2016-05-01

    Mitochondrial fusion is essential for maintenance of mitochondrial function and requires the prohibitin ring complex subunit prohibitin-2 (PHB2) at the mitochondrial inner membrane. Loss of the stomatin/PHB/flotillin/HflK/C (SPFH) domain containing protein PHB2 causes mitochondrial dysfunction and defective mitochondria-mediated signaling, which is implicated in a variety of human diseases, including progressive renal disease. Here, we provide evidence of additional, extra-mitochondrial functions of this membrane-anchored protein. Immunofluorescence and immunogold labeling detected PHB2 at mitochondrial membranes and at the slit diaphragm, a specialized cell junction at the filtration slit of glomerular podocytes. PHB2 coprecipitated with podocin, another SPFH domain-containing protein, essential for the assembly of the slit diaphragm protein-lipid supercomplex. Consistent with an evolutionarily conserved extra-mitochondrial function, the ortholog of PHB2 in Caenorhabditis elegans was also not restricted to mitochondria but colocalized with the mechanosensory complex that requires the podocin ortholog MEC2 for assembly. Knockdown of phb-2 partially phenocopied loss of mec-2 in touch neurons of the nematode, resulting in impaired gentle touch sensitivity. Collectively, these data indicate that, besides its established role in mitochondria, PHB2 may have an additional function in conserved protein-lipid complexes at the plasma membrane. PMID:27105734

  5. Level of urinary liver-type fatty acid-binding protein is associated with cardiac markers and electrocardiographic abnormalities in type-2 diabetes with chronic kidney disease stage G1 and G2.

    PubMed

    Maeda, Yoshiteru; Suzuki, Atsushi; Ishii, Junnichi; Sekiguchi-Ueda, Sahoko; Shibata, Megumi; Yoshino, Yasumasa; Asano, Shogo; Hayakawa, Nobuki; Nakamura, Kazuhiro; Akiyama, Yasukazu; Kitagawa, Fumihiko; Sakuishi, Toshiaki; Fujita, Takashi; Hashimoto, Shuji; Ozaki, Yukio; Itoh, Mitsuyasu

    2015-05-01

    Urinary liver-type fatty acid-binding protein (L-FABP) reflects the degree of stress in proximal tubules of the kidney. We examined the level of L-FABP in type-2 diabetes mellitus (T2DM) patients with chronic kidney disease (CKD) stage G1 and G2, and its relationship with cardiac markers and electrocardiographic (ECG) abnormalities. T2DM patients whose estimated glomerular filtration rate (eGFR) was ≥60 mL/min/1.73 m(2) were recruited [n = 276 (165 males), mean age 64 years]. The median level of urinary L-FABP was 6.6 μg/gCr. Urinary L-FABP showed significant correlation with urinary albumin-to-creatinine ratio (ACR) (r = 0.51, p < 0.0001). Median (25th-75th percentile) eGFR was 82 (72-95) mL/min/1.73 m2. We divided patients into four subgroups (group 1, L-FABP ≤8.4 μg/gCr and ACR ≤30 mg/gCr; group 2, L-FABP ≤8.4 μg/gCr and ACR >30 mg/gCr; group 3, L-FABP >8.4 μg/gCr and ACR ≤30 mg/gCr; group 4, L-FABP >8.4 μg/gCr and ACR >30 mg/gCr). Compared with group 1, group 4 was significantly higher in systolic blood pressure, and eGFR using standardized serum cystatin C, high-sensitivity troponin T, and N-terminal pro-brain natriuretic peptide (NT-proBNP). Group 4 had significantly higher level of NT-proBNP than group 3. Groups 2, 3 and 4 showed more ECG abnormalities than group 1. These findings suggest that simultaneous measurement of urinary L-FABP and ACR should be useful to assess cardiovascular damage reflecting on the elevation of cardiac markers and ECG abnormalities in T2DM with CKD G1 and G2. PMID:24626813

  6. Transfer and transport of aluminum in filtration unit.

    PubMed

    Wen-dong, Wang; Hong-wei, Yang; Hua-zhang, Zhao; Zhan-peng, Jiang

    2007-01-01

    Aluminum salt coagulants were used prevalently in various water works. In this article, the effects of filtration on residual aluminum concentration and species distribution were researched by determining the concentration of different aluminum species before and after single layer filter, double layer filter, and membrane filtration units. In the research, size exclusion chromatography (SEC) was used to separate colloidal and soluble aluminum, ion exchange chromatography (IEC) was used to separate organic and inorganic aluminum, and inductivity coupled plasma-atomic emission spectrometry (ICP-AES) was used to determine the aluminum concentration. The results showed that the rapid filtration process had the ability of removing residual aluminum from coagulant effluent water, and that double layer filtration was more effective in residual aluminum removal than single layer filtration, while nano filtration was more effective than micro filtration. It was found that when the residual aluminum concentration was below 1 mg/L in sediment effluent, the residual aluminum concentration in treated water was above 0.2 mg/L. The direct rapid filtration process mainly removed the suspended aluminum. The removal of soluble and colloidal aluminum was always less than 10% and the natural small particles that adsorbed the amount of soluble or small particles aluminum on their surface were difficult to be removed in this process. Micro filtration and nano filtration were good technologies for removing aluminum; the residual aluminum concentration in the effluent was less than 0.05 mg/L. PMID:17966844

  7. Breakthrough of cyanobacteria in bank filtration.

    PubMed

    Pazouki, Pirooz; Prévost, Michèle; McQuaid, Natasha; Barbeau, Benoit; de Boutray, Marie-Laure; Zamyadi, Arash; Dorner, Sarah

    2016-10-01

    The removal of cyanobacteria cells in well water following bank filtration was investigated from a source water consisting of two artificial lakes (A and B). Phycocyanin probes used to monitor cyanobacteria in the source and in filtered well water showed an increase of fluorescence values demonstrating a progressive seasonal growth of cyanobacteria in the source water that were correlated with cyanobacterial biovolumes from taxonomic counts (r = 0.59, p < 0.00001). A strong correlation was observed between the cyanobacterial concentrations in the lake water and in the well water as measured by the phycocyanin probe (p < 0.001, 0.73 ≤ r(2) ≤ 0.94). Log removals from bank filtration estimated from taxonomic counts ranged from 0.96 ± (0.5) and varied according to the species of cyanobacteria. Of cyanobacteria that passed through bank filtration, smaller cells were significantly more frequent in well water samples (p < 0.05) than larger cells. Travel times from the lakes to the wells were estimated as 2 days for Lake B and 10 days for Lake A. Cyanobacterial species in the wells were most closely related to species found in Lake B. Thus, a travel time of less than 1 week permitted the breakthrough of cyanobacteria to wells. Winter samples demonstrated that cyanobacteria accumulate within bank filters, leading to continued passage of cells beyond the bloom season. Although no concentrations of total microcystin-LR were above detection limits in filtered well water, there is concern that cyanobacterial cells that reach the wells have the potential to contain intracellular toxins. PMID:27343842

  8. A rigid porous filter and filtration method

    SciTech Connect

    Chiang, Ta-Kuan; Straub, Douglas, Straub L.; Dennis, Richard A.

    1998-12-01

    The present invention involves a porous rigid filter comprising a plurality of concentric filtration elements having internal flow passages and forming external flow passages there between. The present invention also involves a pressure vessel containing the filter for the removal of particulate from high pressure particulate containing gases, and further involves a method for using the filter to remove such particulate. The present filter has the advantage of requiring fewer filter elements due to the high surface area- to-volume ratio provided by the filter, requires a reduced pressure vessel size, and exhibits enhanced mechanical design properties, improved cleaning properties, configuration options, modularity and ease of fabrication.

  9. Granulocyte kinetics in donors undergoing filtration leukapheresis.

    PubMed

    Rubins, J M; MacPherson, J L; Nusbacher, J; Wiltbank, T

    1976-01-01

    Normal blood donors undergoing filtration leukapheresis (FL) have a profound transient neutropenia early in the procedure which is followed by a "rebound" neutrophilia. This phenomenon occurs in unstimulated donors as well as in donors pretreated with either prednisone or dexamethasone. The mechanism for development of the neutropenia was investigated in volunteers throug a nylon filter at 37 C, a significant but transient neutropenia was observed. Plasma rendered cell and stroma-free achieved the same result indicating that plasma alone, when exposed to nylon fibers, is capable of producing neutropenia. PMID:1251458

  10. Electrospinning of nanofibers for filtration media

    NASA Astrophysics Data System (ADS)

    Park, Hyoungjun

    Since particulate impurity is regarded as the primary cause of lung diseases, purification of air has been a crucial issue. Filtration is the most conventional method to obtain clean air, whereby particulate matter is collected on a fibrous media. The use of fibrous filters is prevalent because of their high filtration efficiency and low pressure drop. Fibrous filters were fabricated via the electrospinning process which can be used to produce continuous submicron-diameter sized fibers. Polyacrylonitrile (PAN) nanofibers with a mean fiber diameter of 224 nm were electrospun to form fibermats. Filtration tests on fibermats of PAN were conducted to confirm that filters of thinner fibers result in higher collection efficiencies and lower pressure drops than that of thicker fibers as predicted by the theoretical filtration mechanism. Results showed that electrospun PAN nanofibermats had a superior quality factor of 0.067+/-0 compared to 0.031+/-0.001 by the current state-of-the-art microfiber-based high particulate air (HEPA) filtration media. The verified theory implies that nanofibermats of other types of materials could also be considered as promising filtration media since filtration performance is independent of the material used. As materials for advanced next-generation filtration media, ceramics are favored over polymeric materials due to their robustness against environmental factors such as ultraviolet rays, abrasive particles, and high temperature all of which degrade and damage the fibrous structure. Amidst various ceramic materials, the anatase phase of TiO2 was selected due to its mechanical property and versatility as a photocatalyst and microwave-absorbing material. Anatase TiO2 fibers were fabricated by electrospinning followed by heat treatment at 500°C for 3 hours. However, early precipitation or gelation of the organic solvent-based TiO2 sol posed a practical challenge in the sample preparation. In order to enhance stability of the precursor sol, a

  11. Electrokinetic filtration in clays: theory and experiments.

    PubMed

    Musso, Guido; Francia, Carlotta; Maja, Mario; Spinelli, Paolo

    2002-10-01

    The main aspects and results of some electrokinetic filtration tests are presented. Both theory and tests show the key role played by the electrochemical boundary phenomena, such as the electrode reactions, and by the mineralogy of the soil. The aforementioned results show the necessity to run long duration tests. Indeed the macroscopic properties of the soil can change widely during the tests, therefore affecting the expected results in terms of environmental remediation or consolidation but also in terms of energy consumption and efficiency. PMID:12489264

  12. Investigation of Microgranular Adsorptive Filtration System

    NASA Astrophysics Data System (ADS)

    Cai, Zhenxiao

    Over the past few decades, enormous advances have been made in the application of low-pressure membrane filtration to both drinking water and wastewater treatment. Nevertheless, the full potential of this technology has not been reached, due primarily to limitations imposed by membrane fouling. In drinking water treatment, much of the fouling is caused by soluble and particulate natural organic matter (NOM). Efforts to overcome the problem have focused on removal of NOM from the feed solution, usually by addition of conventional coagulants like alum and ferric chloride (FeCl3) or adsorbents like powdered activated carbon (PAC). While coagulants and adsorbents can remove a portion of the NOM, their performance with respect to fouling control has been inconsistent, often reducing fouling but sometimes having no effect or even exacerbating fouling. This research investigated microgranular adsorptive filtration (muGAF), a process that combines three existing technologies---granular media filtration, packed bed adsorption, and membrane filtration---in a novel way to reduce membrane fouling while simultaneously removing NOM from water. In this technology, a thin layer of micron-sized adsorbent particles is deposited on the membrane prior to delivering the feed to the system. The research reported here represents the first systematic study of muGAF, and the results demonstrate the promising potential of this process. A new, aluminum-oxide-based adsorbent---heated aluminum oxide particles (HAOPs)---was synthesized and shown to be very effective for NOM removal as well as fouling reduction in muGAF systems. muGAF has also been demonstrated to work well with powdered activated carbon (PAC) as the adsorbent, but not as well as when HAOPs are used; the process has also been successful when used with several different membrane types and configurations. Experiments using a wide range of operational parameters and several analytical tools lead to the conclusion that the fouling

  13. Ictal Cardiac Ryhthym Abnormalities

    PubMed Central

    Ali, Rushna

    2016-01-01

    Cardiac rhythm abnormalities in the context of epilepsy are a well-known phenomenon. However, they are under-recognized and often missed. The pathophysiology of these events is unclear. Bradycardia and asystole are preceded by seizure onset suggesting ictal propagation into the cortex impacting cardiac autonomic function, and the insula and amygdala being possible culprits. Sudden unexpected death in epilepsy (SUDEP) refers to the unanticipated death of a patient with epilepsy not related to status epilepticus, trauma, drowning, or suicide. Frequent refractory generalized tonic-clonic seizures, anti-epileptic polytherapy, and prolonged duration of epilepsy are some of the commonly identified risk factors for SUDEP. However, the most consistent risk factor out of these is an increased frequency of generalized tonic–clonic seizures (GTC). Prevention of SUDEP is extremely important in patients with chronic, generalized epilepsy. Since increased frequency of GTCS is the most consistently reported risk factor for SUDEP, effective seizure control is the most important preventive strategy. PMID:27347227

  14. Abnormal uterine bleeding.

    PubMed

    Whitaker, Lucy; Critchley, Hilary O D

    2016-07-01

    Abnormal uterine bleeding (AUB) is a common and debilitating condition with high direct and indirect costs. AUB frequently co-exists with fibroids, but the relationship between the two remains incompletely understood and in many women the identification of fibroids may be incidental to a menstrual bleeding complaint. A structured approach for establishing the cause using the Fédération International de Gynécologie et d'Obstétrique (FIGO) PALM-COEIN (Polyp, Adenomyosis, Leiomyoma, Malignancy (and hyperplasia), Coagulopathy, Ovulatory disorders, Endometrial, Iatrogenic and Not otherwise classified) classification system will facilitate accurate diagnosis and inform treatment options. Office hysteroscopy and increasing sophisticated imaging will assist provision of robust evidence for the underlying cause. Increased availability of medical options has expanded the choice for women and many will no longer need to recourse to potentially complicated surgery. Treatment must remain individualised and encompass the impact of pressure symptoms, desire for retention of fertility and contraceptive needs, as well as address the management of AUB in order to achieve improved quality of life. PMID:26803558

  15. Comparison of Garnet Bead Media Filtration and Multimedia Filtration for Turbidity and Microbial Pathogen Removal

    EPA Science Inventory

    U.S. Environmental Protection Agency’s (EPA’s) National Risk Management Research Laboratory (NRMRL) in Cincinnati, Ohio is evaluating drinking water filtration systems to determine their capability to meet the requirements of the Long-Term 2 Enhanced Surface Water Treatment Rule ...

  16. Co-existence of thin basement membrane nephropathy with other glomerular pathologies; a single center experience

    PubMed Central

    Qazi, Rizwan A.; Bastani, Bahar

    2015-01-01

    Background: The co-existence of thin basement membrane nephropathy (TBMN) and another glomerular pathology portends a worse prognosis than TBMN alone. Objectives: The purpose of our study was to investigate the prevalence of TBMN and associated glomerular pathologies at our institution. Patients and Methods: We reviewed all renal biopsies performed at Saint Louis University hospital over a 7-year period. We excluded all post transplant biopsies, and biopsies showing diabetic glomerulopathy, membranoproliferative glomerulopathy, membranous glomerulopathy, and biopsies where no electron microscopy or immunofluorescent studies were done. All other biopsies were included. Results: A total of 634 biopsies were included in the study. The prevalence of TBMN was 47 (7.4%), of whom 17 (36.2%) had TBMN alone. In the remaining 30 (63.8%) patients TBMN was associated with other glomerular pathologies: IgAN 9 (19.1%) and FSGS 9 (19.1%). We found significantly higher prevalence of IgAN in patients with TBMN versus all biopsies (19.1% vs. 7.7%, respectively, P = 0.002). We found significant similarities in biopsy indications for TBMN and IgAN group. Conclusions: Around two thirds of the cases of TBMN were associated with other glomerular pathologies. The prevalence of IgAN, but not focal segmental glomerulosclerosis, was significantly higher in patients with TBMN as compared to the general renal biopsy specimens. PMID:25964888

  17. Glomerular endothelial cell injury and cross talk in diabetic kidney disease.

    PubMed

    Fu, Jia; Lee, Kyung; Chuang, Peter Y; Liu, Zhihong; He, John Cijiang

    2015-02-15

    Diabetic kidney disease (DKD) remains a leading cause of new-onset end-stage renal disease (ESRD), and yet, at present, the treatment is still very limited. A better understanding of the pathogenesis of DKD is therefore necessary to develop more effective therapies. Increasing evidence suggests that glomerular endothelial cell (GEC) injury plays a major role in the development and progression of DKD. Alteration of the glomerular endothelial cell surface layer, including its major component, glycocalyx, is a leading cause of microalbuminuria observed in early DKD. Many studies suggest a presence of cross talk between glomerular cells, such as between GEC and mesangial cells or GEC and podocytes. PDGFB/PDGFRβ is a major mediator for GEC and mesangial cell cross talk, while vascular endothelial growth factor (VEGF), angiopoietins, and endothelin-1 are the major mediators for GEC and podocyte communication. In DKD, GEC injury may lead to podocyte damage, while podocyte loss further exacerbates GEC injury, forming a vicious cycle. Therefore, GEC injury may predispose to albuminuria in diabetes either directly or indirectly by communication with neighboring podocytes and mesangial cells via secreted mediators. Identification of novel mediators of glomerular cell cross talk, such as microRNAs, will lead to a better understanding of the pathogenesis of DKD. Targeting these mediators may be a novel approach to develop more effective therapy for DKD. PMID:25411387