Renal Extraction of Para-Aminohippurate in Infants and Children
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Note on the Interpretation of Clearance Methods in the Diseased Kidney
NOTE ON THE INTERPRETATION OF CLEARANCE METHODS IN THE DISEASED KIDNEY Homer W. Smith J Clin Invest. 1941;20(6):631-635. https://doi.org/10.1172/JCI101256. Research Article Find the latest version: https://jci.me/101256/pdf NOTE ON THE INTERPRETATION OF CLEARANCE METHODS IN THE DISEASED KIDNEY By HOMER W. SMITH (From the Department of Physiology, New York University CoUlege of Medicine, New York City) (Received for publication June 16, 1941) In interpreting the results obtained by clear- but only by investigation; but since by definition they are ance methods in the diseased kidney, the physio- unable to excrete diodrast they do not contribute to CD or TmD. logical limitations of these methods must be kept All renal parenchyma which normally lacks excretory clearly in mind. Since there has been no oppor- function, or which has lost its excretory function, will be tunity to discuss these limitations generally, it designated as inert tissue. This would include capsular has seemed desirable to emphasize certain more and connective tissue, impotent nephrons as defined above, important points in this note. injured nephrons which permit the back-diffusion of inulin and other constituents of the tubular urine, nephrons which The four methods to be considered here are are obstructed by casts or disconnected from collecting the inulin clearance (CIN), the plasma diodrast ducts so that urine formation is impossible, and fibrotic clearance (CD), the maximal rate of tubular ex- glomeruli and tubular fragments generally. cretion of diodrast (TmD) and the maximal rate of tubular reabsorption of glucose (TmG), all Total renal function and function in four methods being based on overall measure- individual nephrons ments made on the two kidneys by the collection Recognizing that there are two million-odd of bladder urine (4, 10, 12). -
ANS: 600 Ml/Min This Is the Renal Plasma Flow, Which Is Given As the Clearance of PAH
Bio390 Clearance and Reabsorption thanks to Dr. J.F. Anderson, Dept Zoology Univ. of Florida, Gainesville Use the following data to answer these questions. 100 ml renal inulin clearance: min 0.5 mg [inulin]arterial plasma: ml hematocrit: 0.40 600 ml renal PAH clearance: min 0.8 mg [glucose]arterial plasma: ml 0.0 mg [glucose]urine: ml 0.5 ml rate of urine formation: min ESTIMATE: a. plasma flow rate in the afferent arterioles: ANS: 600 mL/min This is the renal plasma flow, which is given as the Clearance of PAH. b. plasma flow rate in the efferent arterioles: ANS: This will be the renal plasma flow rate (RPF) minus the amount that the plasma volume is reduced by filtration. The amount of plasma lost by filtration must equal the GFR which is the clearance of inulin (100 ml/min here). Thus, the blood flow 1 in the efferent arteriole is 600 - 100 ml/min = 500 ml/min in this problem c. plasma flow rate in the renal veins: ANS: by the time that blood enters the veins, nearly all of the water lost during filtration has made its way back to the blood (especially if the subject is dehydrated!). If urine is being formed at a rate of 0.5 mL/min, then that represents (essentially) the volume of water lost per min. So, the renal venous plasma flow rate = RPF- urine loss = 600 - 0.5 = 599.5 ml/min d. renal blood flow rate in renal artery in ml/min ANS: 833 mL/min the hct = 40% (0.4). -
Impaired Tubular Secretion of Organic Solutes in Acute Kidney Injury
Original Investigation Impaired Tubular Secretion of Organic Solutes in Acute Kidney Injury Frank J. O’Brien,1 Robert D. Mair,2,3 Natalie S. Plummer,2,3 Timothy W. Meyer,2,3 Scott M. Sutherland,4 and Tammy L. Sirich2,3 Abstract Background Impairment of kidney function is routinely assessed by measuring the accumulation of creatinine, an organic solute cleared largely by glomerular filtration. We tested whether the clearance of solutes that undergo tubular secretion is reduced in proportion to the clearance of creatinine in humans with AKI. Methods Four endogenously produced organic solutes (phenylacetylglutamine [PAG], hippurate [HIPP], indoxyl sulfate [IS], and p-cresol sulfate [PCS]) were measured in spot urine and plasma samples from ten patients with AKI and 17 controls. Fractional clearance relative to creatinine was calculated to assess tubular secretion. Fractional clearance values were calculated in terms of the free, unbound levels of HIPP, IS, and PCS that bind to plasma proteins. Results Fractional clearance values for PAG, HIPP, IS, and PCS were .1.0 in patients with AKI as well as controls, indicating that these solutes were still secreted by the tubules of the injured kidneys. Fractional clearance values were, however, significantly lower in patients with AKI than controls, indicating that kidney injury reduced tubular secretion more than glomerular filtration (AKI versus control: PAG, 2.160.7 versus 4.661.4, P,0.001; HIPP, 1065 versus 1567, P50.02; IS, 1066 versus 2867, P,0.001; PCS, 3.361.8 versus 1063, P,0.001). Free plasma levels rose out of proportion to total plasma levels for each of the bound solutes in AKI, so that calculating their fractional clearance in terms of their total plasma levels failed to reveal their impaired secretion. -
Dmd.117.077586.Full.Pdf
DMD Fast Forward. Published on November 21, 2017 as DOI: 10.1124/dmd.117.077586 This article has not been copyedited and formatted. The final version may differ from this version. DMD # 77586 Discovery and Validation of Pyridoxic Acid and Homovanillic Acid as Novel Endogenous Plasma Biomarkers of Organic Anion Transporter (OAT) 1 and OAT3 in Cynomolgus Monkeys Downloaded from dmd.aspetjournals.org Hong Shen, David M. Nelson, Regina V. Oliveira, Yueping Zhang, Colleen A. Mcnaney, Xiaomei Gu, Weiqi Chen, Ching Su, Michael D. Reily, Petia A. Shipkova, Jinping Gan, Yurong Lai, Punit Marathe, and W. Griffith Humphreys at ASPET Journals on September 29, 2021 Departments of Metabolism and Pharmacokinetics (H.S., Y.Z., X.G., W.C., J.G., Y.L., P.M., W.G.H.), Discovery Toxicology (D.N., C.A.M., M.D.R.), Bioanalytical Research (R.O., P.A.S.), and Discovery Pharmaceutics (C.S.), Pharmaceutical Candidate Optimization, Bristol-Myers Squibb Research and Development, Princeton, New Jersey 08543, United States 1 DMD Fast Forward. Published on November 21, 2017 as DOI: 10.1124/dmd.117.077586 This article has not been copyedited and formatted. The final version may differ from this version. DMD # 77586 Running title: Identification of functional plasma markers of OAT1 and OAT3 in vivo Address correspondence to: Dr. Hong Shen Department of Metabolism and Pharmacokinetics (MAP) Pharmaceutical Candidate Optimization (PCO) Downloaded from Bristol-Myers Squibb Company (BMS) Route 206 & Province Line Road, Princeton, NJ 08543-4000 Telephone: (609) 252-4509 dmd.aspetjournals.org Facsimile: (609) 252-6802 E-mail: [email protected] at ASPET Journals on September 29, 2021 Number of text pages: 29 Number of tables: 3 Number of figures: 6 Number of references: 39 Number of words: Abstract: 249 Introduction: 794 Discussion: 1832 Abbreviations: Ae, amount of unchanged drug recovered in the urine; AUC, area under the plasma concentration-time curve; CCK-8, cholecystokinin octapeptide; CE, collision energy; CLNR, 2 DMD Fast Forward. -
Production of Hypertonic Urine in the Absence of Pituitary Antidiuretic Hormone
Production of Hypertonic Urine in the Absence of Pituitary Antidiuretic Hormone Robert W. Berliner, Douglas G. Davidson J Clin Invest. 1957;36(10):1416-1427. https://doi.org/10.1172/JCI103541. Research Article Find the latest version: https://jci.me/103541/pdf PRODUCTION OF HYPERTONIC URINE IN THE ABSENCE OF PITUITARY ANTIDIURETIC HORMONE 1 BY ROBERT W. BERLINER AND DOUGLAS G. DAVIDSON 2 (From the Laboratory of Kidney and Electrolyte Metabolism, National Heart Institute, National Institutes of Health, Public Health Sertice, Department of Health, Education, and Welfare, Bethesda, Md.) (Submitted for publication May 1, 1957; accepted May 23, 1957) The mechanism by which pituitary antidiuretic permeability of the tubule membrane to water. hormone (ADH) produces its renal effect has The change to hypertonicity cannot be so readily not been clearly established. Under ordinary con- attributed to an effect on water permeability with- ditions, in the absence of ADH, urine of a con- out some assumptions as to the mechanism by centration considerably below that of plasma is which the hypertonicity is produced. However, produced in large volume. With increasing it is a reasonable hypothesis that the mechanism amounts of ADH, administered or secreted, the for the production of hypertonicity is not depen- osmotic pressure of the urine rises to and above dent upon ADH but that its effects are unmasked, that of plasma. With respect to total water bal- in the presence of ADH, by 1) changes in the vol- ance, the quantitatively more important contri- ume and concentration of urine delivered to it and, bution to water economy is the change between possibly, 2) changes in the permeability of the maximally dilute and isotonic urine, since this, in membranes separating the concentrating mecha- normal man, may involve a change in water ex- nism from the urine in the tubule lumen. -
A Compendium of Research
NASA TECHNICAL NASA TM X-3308 MEMORANDUM CO CO I X c PHYSIOLOGIC RESPONSES TO WATER IMMERSION IN MAN: A COMPENDIUM OF RESEARCH James Kollias, Dena Van Derveer, Karen J. Dorchak, and John E. Greenleaf Ames Research Center Moffett Field, Calif. 94035 ^ *" /V NATIONAL AERONAUTICS AND SPACE ADMINISTRATION • WASHINGTON, D. C. • FEBRUARY 1976 1. Report No. 2. Government Accession No. 3. Recipient's Catalog No. NASA TM X-3308 4. Title and Subtitle 5. Report Date February 1976 PHYSIOLOGIC RESPONSES TO WATER IMMERSION IN MAN: 6. Performing Organization Code A COMPENDIUM OF RESEARCH 7. Author(s) 8. Performing Organization Report No. A-6038 James Kollias, Dena Van Derveer, Karen J. Dorchak, and John E. Greenleaf 10. Work Unit No. 9. Performing Organization Name and Address 970-21-14-05 NASA Ames Research Center 11. Contract or Grant No. Moffett Field, Calif. 94035 13. Type of Report and Period Covered 12. Sponsoring Agency Name and Address Technical Memorandum National Aeronautics and Space Administration 14. Sponsoring Agency Code Washington, D. C. 20546 15. Supplementary Notes 16. Abstract Since the advent of space flight programs, scientists have been searching for ways to reproduce the zero-gravity effects of weightlessness. Brief periods of weightlessness up to 1 minute were feasible using Keplerian trajectory, but comprehen- sive study of the prolonged effects of the weightless state necessitated the development of other methods. Thus far the two approaches most widely used have been complete bedrest and fluid immersion. Surprisingly, these simulated environments have produced essentially all of the symptoms found in astronauts. This compendium contains reports appearing in the literature through December 1973. -
Acute Blood Loss
Therapeutics in Practice Acute Blood Loss Column Editor K. Gary Magdesian, DVM, DACVIM, DACVECC, DACVCP University of California, Davis Debra Deem Morris, DVM, MS, DACVIM Acute hemorrhage, a form of hypovolemic shock, can result from external or internal 190 State Route 10 blood loss. Distinguishing between these two types of hemorrhage is important to ren - dering proper therapy because cases of controllable hemorrhage must be treated differ - East Hanover, NJ 07936 ently than cases of uncontrollable hemorrhage. • phone 973-599-1191 • fax 973-599-1193 PATHOPHYSIOLOGY OF HEMORRHAGIC SHOCK • email stretchdee m@ yahoo.com Acute hemorrhage results in hypovolemia and a reduction in oxygen-carrying capac - ity (hemoglobin). A blood volume loss of 15% to 20% is clinically detectable, while life-threatening circulatory failure occurs with a blood volume loss of 30% to 40%. 1 Compensatory physiologic mechanisms include vasoconstriction, increased cardiac contractility, and tachycardia (activation of the sympathetic nervous system). In addi - tion, the drop in hydrostatic pressure due to hypovolemia causes filtration fraction to diminish and lymphatic flow to increase as a result of sympathetic activation and a reduction in central venous pressure (CVP). These changes result in a net movement of interstitial fluid into the vascular space. Simultaneously, the renin–angiotensin– aldosterone system is activated, resulting in a decreased glomerular filtration rate, decreased urine production and enhanced renal sodium resorption, increased thirst, and vasoconstriction. Vasopressin contributes to vasoconstriction and thirst. These compensatory mechanisms can maintain circulation in cases of mild blood loss (up to a volume loss of 15%). Losses exceeding this amount require volume replacement and are beyond physiologic compensation. -
1) an Increase in the Concentration of Plasma Potassium Causes Increase I
Select the one that is the best answer: 1) An increase in the concentration of plasma potassium causes increase in : a) release of renin b) secretion of aldosterone c) secretion of ADH d) release of natriuretic hormone e) production of angiotensin II . 2) Amino acids are almost completely reabsorbed from the glomerular filtrate via active transport in the : a) proximal tubule b) loop of Henle c) distal tubule d) collecting duct e) renal pelvis 3) Glomerular filtration rate would be increased by : a) constriction of the afferent arteriole b) a decrease in afferent arteriolar pressure c) compression of the renal capsule d) a decrease in the concentration of plasma protein e) a decrease in renal blood flow 4) The greatest amount of hydrogen ion secreted by the proximal tubule is associated with : a) excretion of potassium ion b) excretion of hydrogen ion c) reabsorption of calcium ion d) reabsorption of bicarbonate ion e) reabsorption of phosphate ion 5) In controlling the synthesis and secretion of aldosterone , which of the following factors is least important ? a) renin b) angiotensin II c) concentration of plasma Na+ d) concentration of plasma K+ e) adrenocorticotropic hormone ( ACTH ) 6) Renal correction of acute hyperkalemia will result in : a) alkalosis b) acidosis - c) increased secretion of HCO3 d) increased secretion of H+ e) increased secretion of Na+ 7) Most of the glucose that is filtered through the glomerulus undergoes reabsorption in the : a) proximal tubule b) descending limp of the loop of Henle c) ascending limb of the loop of Henle d) distal tubule e) collecting duct 8) Ammonia is an affective important urinary buffer for which of the following reasons : a) its production in the kidney decrease during chronic acidosis b) the walls of the renal tubules are impermeable to NH3 c) the walls of the renal tubules are impermeable to NH3 d) its acid base reaction has a low pKa e) none of the above . -
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https://theses.gla.ac.uk/ Theses Digitisation: https://www.gla.ac.uk/myglasgow/research/enlighten/theses/digitisation/ This is a digitised version of the original print thesis. Copyright and moral rights for this work are retained by the author A copy can be downloaded for personal non-commercial research or study, without prior permission or charge This work cannot be reproduced or quoted extensively from without first obtaining permission in writing from the author The content must not be changed in any way or sold commercially in any format or medium without the formal permission of the author When referring to this work, full bibliographic details including the author, title, awarding institution and date of the thesis must be given Enlighten: Theses https://theses.gla.ac.uk/ [email protected] The Development of HPLC Methods for the Determination of Methotrexate and Doxorubicin Metabolites and their Application to Clinical Studies. Yahya Yahya Zeki Farid BSc PhD University of Glasgow Department of Pathological Biochemistry Faculty of Medicine JUNE 1983 X s. HERON LTD 5 QUEENS CRESCENT ST. GEORGES CROSS GLASGOW 041 332 1883 ProQuest Number: 10646152 All rights reserved INFORMATION TO ALL USERS The quality of this reproduction is dependent upon the quality of the copy submitted. In the unlikely event that the author did not send a com plete manuscript and there are missing pages, these will be noted. Also, if material had to be removed, a note will indicate the deletion. uesL ProQuest 10646152 Published by ProQuest LLO (2017). Copyright of the Dissertation is held by the Author. -
Renal Function in Mice: Effects of Volume Expansion and Angiotensin II
J Am Soc Nephrol 10: 2631–2636, 1999 Renal Function in Mice: Effects of Volume Expansion and Angiotensin II LUDEK CERVENKA,* KENNETH D. MITCHELL,† and L. GABRIEL NAVAR† *Department of Experimental Medicine, Institute for Clinical and Experimental Medicine, Prague, Czech Republic; and †Department of Physiology, Tulane University School of Medicine, New Orleans, Louisiana. Abstract. The present study was performed to validate a simple (83 6 2 mmHg), but led to significantly greater values in both means for assessing renal function in anesthetized mice and to GFR and RPF (1.35 6 0.14 versus 1.01 6 0.1 ml/min z g and characterize the renal hemodynamic responses to acute volume 11.26 6 1.39 versus 6.29 6 0.5 ml/min z g, respectively). expansion and how these responses are altered by concurrent Infusion of AngII during volume expansion led to significant angiotensin II (AngII) infusions. Inulin and para-aminohippu- elevations of MAP (100 6 3 mmHg, P , 0.05) and prevented rate clearances were used to assess GFR and renal plasma flow the increases in GFR and RPF elicited by volume expansion (RPF) in three groups of male C57Bl/6 mice anesthetized with (0.77 6 0.08 and 5.35 6 0.48 ml/min z g, respectively). inactin (100 mg/kg, intraperitoneally) and ketamine (10 mg/ Volume expansion also elicited marked increases in absolute kg). To avoid the hypotension associated with repeated blood and fractional sodium excretion (6.1 6 1.0 versus 0.62 6 0.2 sampling, a single blood sample was taken after three timed mEq/min z g and 3.1 6 0.7 versus 0.4 6 0.1%, respectively). -
Relationship Between Renin and Intrarenal Hemodynamics in Hemorrhagic Hypotension
Relationship between renin and intrarenal hemodynamics in hemorrhagic hypotension A. Grandchamp, … , J. R. Scherrer, B. Truniger J Clin Invest. 1971;50(5):970-978. https://doi.org/10.1172/JCI106590. Research Article In order to investigate the possible role of the renin-angiotensin system in the regulation of intrarenal hemodynamics in hemorrhagic hypotension (HH), seven mongrel dogs have been studied under the following conditions: (a) Control, (b) HH (mean arterial pressure 70 mm Hg), and (c) HH + alpha adrenergic blockade by phenoxybenzamine (HH + POB). The following parameters were obtained for the right kidney: Intrarenal distribution of blood flow and local blood flow rates (133Xe washout technique); total renal blood flow (RBF) on the basis of the clearance and extraction ratio of PAH and the arterial hematocrit; plasma renin concentrations in the renal artery and vein by the method of Boucher and his associates; and renin release into the renal circulation. Alpha adrenergic blockade reverted the typical redistribution of intrarenal blood flow observed under HH. In hemorrhage, arterial and venous renin concentrations increased by a factor of 3.4 and 4.8 respectively. A further small increase was observed during HH + POB with the respective factors increasing to 4.8 and 5.3, as compared with control values. The renin release into the circulation increased by a factor of 1.2 in HH and 4.0 in HH + POB. Whereas in HH there seemed to be a relationship between increased renin concentrations or renin release, and the redistribution of blood flow, no such correlation was found […] Find the latest version: https://jci.me/106590/pdf Relationship between Renin and Intrarenal Hemodynamics in Hemorrhagic Hypotension A. -
Discovery and Validation of Pyridoxic Acid and Homovanillic Acid As
Supplemental material to this article can be found at: http://dmd.aspetjournals.org/content/suppl/2017/11/21/dmd.117.077586.DC1 1521-009X/46/2/178–188$25.00 https://doi.org/10.1124/dmd.117.077586 DRUG METABOLISM AND DISPOSITION Drug Metab Dispos 46:178–188, February 2018 Copyright ª 2018 by The American Society for Pharmacology and Experimental Therapeutics Discovery and Validation of Pyridoxic Acid and Homovanillic Acid as Novel Endogenous Plasma Biomarkers of Organic Anion Transporter (OAT) 1 and OAT3 in Cynomolgus Monkeys s Hong Shen, David M. Nelson, Regina V. Oliveira, Yueping Zhang, Colleen A. Mcnaney, Xiaomei Gu, Weiqi Chen, Ching Su, Michael D. Reily, Petia A. Shipkova, Jinping Gan, Yurong Lai, Punit Marathe, and W. Griffith Humphreys Departments of Metabolism and Pharmacokinetics (H.S., Y.Z., X.G., W.C., J.G., Y.L., P.M., W.G.H.), Discovery Toxicology (D.M.N.), Bioanalytical and Discovery Analytical Sciences (R.V.O., C.A.M., M.D.R., P.A.S.), and Discovery Pharmaceutics (C.S.), Pharmaceutical Candidate Optimization, Bristol-Myers Squibb Research and Development, Princeton, New Jersey Received July 14, 2017; accepted November 17, 2017 Downloaded from ABSTRACT Perturbation of organic anion transporter (OAT) 1- and OAT3- animals. The plasma of animals was then subjected to targeted mediated transport can alter the exposure, efficacy, and safety of LC-MS/MS analysis, which confirmed that the PDA and HVA AUCs drugs. Although there have been reports of the endogenous increased by approximately 2- to 3-fold by PROB pretreatments. biomarkers for OAT1/3, none of these have all of the characteristics PROB also increased the plasma concentrations of hexadecane- dmd.aspetjournals.org required for a clinical useful biomarker.