DOCSLIB.ORG

Impaired Tubular Secretion of Organic Solutes in Acute Kidney Injury

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
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. Conclusions Tubular secretion of organic solutes can be reduced out of proportion to glomerular filtration in AKI. Impaired secretion of protein-bound solutes may be more reliably detected when clearances are expressed in terms of their free, unbound levels in the plasma. KIDNEY360 1: 724–730, 2020. doi: https://doi.org/10.34067/KID.0001632020 Introduction cleared by the combination of protein binding and The severity of kidney injury is most often assessed by tubular secretion (5,8). A particular aim of this study measuring the plasma creatinine level, which serves as was to assess the effect of AKI on such highly efficient a surrogate for the GFR. Many waste solutes, however, secretory clearances. We therefore calculated the frac- are removed from the body through proximal tubular tional clearance of the protein-bound solutes hippurate, secretion (1–4). This study tested whether renal clear- indoxyl sulfate, and p-cresol sulfate expressed in terms ances of secreted solutes decline in proportion to the of their free, unbound solute levels as well as their total GFR in AKI. The number of secreted solutes is large and solute levels in the plasma. We further assessed the we face the problem of assessing secretory function on effect of impaired secretion on the plasma accumulation the basis of the behavior of a set of them. Our study of normally secreted solutes in patients with AKI and assessed the fractional clearances of four endogenously compared them with solute levels in patients with an- produced organic solutes that are normally cleared by uria on thrice weekly hemodialysis. tubular secretion and are bound to plasma proteins to varying degrees (5). As originally described by Marshall (6,7) the combination of reversible protein binding and Materials and Methods tubular secretion allows the kidney to achieve clearances Patient Enrollment in excess of the renal plasma flow and thereby keep the Ten patients with AKI, 17 controls, and 15 patients free solute levels that body cells are exposed to very low. with anuria on thrice weekly hemodialysis were in- Subsequent studies have identified both endogenous cluded in the study. Patients with AKI were recruited organic solutes and pharmaceuticals that are efficiently from May 2016 to August 2016. Controls and patients 1Department of Medicine, Washington University, St. Louis, Missouri 2Department of Medicine, Stanford University, Palo Alto, California 3Department of Medicine, VA Palo Alto Health Care System, Palo Alto, California 4Department of Pediatrics, Lucile Packard Children’s Hospital, Stanford University, Palo Alto, California Correspondence: Dr. Tammy L. Sirich, Nephrology 111R, Palo Alto VA Health Care System, 3801 Miranda Avenue, Palo Alto, CA 94304. Email: [email protected] 724 Copyright © 2020 by the American Society of Nephrology www.kidney360.org Vol 1 August, 2020 KIDNEY360 1: 724–730, August, 2020 Secretory Impairment in Acute Kidney Injury, O’Brien et al. 725 on hemodialysis were from prior studies (9–11). Written plasma ultrafiltrate concentration divided by the total informed consent was obtained from all participants (in- plasma concentration. cluding written consent from a legally authorized represen- tative for three patients with AKI). The study was approved Statistical Analyses by the Stanford Institutional Review Board and was con- Values for the fractional clearance and free fraction of each ducted in accordance with the Declaration of Helsinki. solute in patients with AKI and controls were compared Patients with AKI were included if they met at least one of using the Mann–Whitney U test. Solute levels among the the Kidney Disease Improving Global Outcomes (KDIGO) hemodialysis, AKI, and control groups were log-transformed 1 $ criteria of ( ) increase in plasma creatinine level 0.3 mg/dl and then compared by ANOVA, with significance of pairwise 2 within 48 hours or ( ) increase in plasma creatinine level comparisons assessed using the Tukey method. Statistical $ 1.5 times baseline within the prior 7 days (12,13). KDIGO analysis was performed using SPSS version 24. criteria were employed to select patients according to a widely recognized categorization; however, individual patients fall- ing within this categorization may vary widely. Patients were Results excluded if they were anuric or if they were receiving heparin The characteristics of the patients with AKI are summa- because heparin causes error in the measurement of the free, rized in Table 1. The patients had been hospitalized for an unbound levels of protein-bound solutes (14). The presumed average of 17618 days before the study, with a range of 4–49 causes of AKI were infection in five patients and cardiovas- days. Their BP averaged 131619/6069 mm Hg and heart cular decompensation in five patients. Nine patients were on rate 92616 beats per minute. The plasma creatinine level antibiotics. Eight patients were on diuretics (two on a loop averaged 3.361.3 mg/dl and plasma urea nitrogen level diuretic only, five on a thiazide and a loop diuretic, and one averaged 89625 mg/dl. The rate of rise was 0.3260.23 mg/dl on a mineralocorticoid blocking agent). Controls were from per day for the plasma creatinine level and 6.263.3 mg/dl a prior study and included if they were .18 years old and per day for plasma urea nitrogen level over a preceding had no known kidney disease (9). Plasma solute levels in period of up to 7 days, for which values are available as patients with AKI and controls were compared with those in illustrated in Supplemental Figure 1 (average 6.261.1 days, patients on hemodialysis from previous studies who were range 4–7 days). Urine output averaged over a 16-hour anuric and maintained on thrice weekly treatment, providing period around the study sample collection averaged adequate treatment by current standards, with single pool 1.760.8 L (range 0.55–2.9 L). The fractional excretion of . Kt/Vurea 1.4 (10,11). sodium was ,1% in three patients and .1% in seven patients, with an average of 4.7%64.9%. Of the ten patients, five who had plasma creatinine level of 3.961.6 mg/dl at the Sample Processing time of sample collection initiated RRT 566 days later, as Simultaneous spot urine and plasma samples were illustrated in Supplemental Figure 2. Four of these five obtained in patients with AKI and controls. Among the patients died during hospitalization at 49644 days after patients with AKI, urine was obtained from a Foley catheter sample collection without recovery of kidney function, and in nine and spontaneously voided in one. Plasma samples in one remained alive on chronic RRT. Of the remaining five patients on hemodialysis were obtained pretreatment at patients who had plasma creatinine 3.061.2 mg/dl at the a midweek session. Free solute levels were measured in time of sample collection, four were discharged 1169 days plasma ultrafiltrate obtained using Nanosep 30K Omega later with creatinine 2.060.4 mg/dl and one died. The separators (Pall, Ann Arbor, MI). Total solute levels were characteristics of the controls and patients on hemodialysis measured in plasma samples deproteinized 1:4 vol:vol with are summarized in Supplemental Table 1. methanol, dried, and reconstituted in water. Urine samples Solute fractional clearances in patients with AKI and were diluted with water to a concentration approximating controls are summarized in Table 2 and depicted in Figure 1. aurineflow of 10 ml/min for patients with AKI and As expected, the fractional clearance of urea in both groups 40 ml/min for controls. Phenylacetylglutamine, hippurate, in- was ,1.0, indicating tubular reabsorption, with a lower doxyl sulfate, and p-cresol sulfate were measured using average value in patients with AKI than in controls stable isotope dilution liquid chromatography with tandem (0.4060.11 versus 0.5760.14; P50.004) indicating greater mass spectrometry as previously described (5). Urea was reabsorption of urea in the setting of acute injury. In con- measured using an enzymatic assay and creatinine was trast, the fractional clearance of phenylacetylglutamine in measured using HPLC.
Load more

Recommended publications
  • 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).
    [Show full text]
  • 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.
    [Show full text]
  • 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.
    [Show full text]
  • 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).
    [Show full text]
  • A Didactic Approach to Renal Clearance
    A Didactic Approach to Renal Clearance Vander Baptista, PhD Department of Physiological Sciences, Centre of Biological Sciences, Federal University of Santa Catarina, 88040-970 Florianópolis, SC – Brazil [email protected] Abstract Renal clearance encompasses a somewhat abstract concept, which makes it a hard-to-visualize phenomenon. It is a confusing topic for students and a difficult task for the instructor to teach. In order to improve or facilitate the teaching-learning process of renal clearance, an alternative strategy is presented here. To properly characterize the components of renal clearance, this didactic model splits renal clearance into two distinct portions of flow rates. The information is organized in a sequential structure, from the simplest ideas to the most complex concepts, assisting both teacher and student in addressing renal clearance. https://doi.org/10.21692/haps.2020.022 Key words: renal clearance, didactic model, cumulative sequence, renal physiology, kidney Introduction The clearance methods are a useful way to quantify the The renal excretion rate of a substance S (ERS) is the amount glomerular filtration rate, tubular reabsorption, and tubular of S removed from the body by the kidneys per unit of time secretion (Hall and Guyton 2011). In a broader vision, as (mg/min). By using the same reasoning, it can be written pointed out by Dr. Donald W. Seldin: “The clearance concept ERS = x US, where is the urinary excretion rate (urinary is central to three critical areas of nephrology”; it was a key volume per unit of time) and US is the concentration of S in feature for understanding the nature of urine formation, for the urine.
    [Show full text]
  • Tion, UV, in the Clearance Calculation, Ie, IV/P = Ously by the Infusion Technique, and on the Appli
    COMPARISON OF THE CONSTANT INFUSION AND URINE COLLECTION TECHNIQUES FOR THE MEASUREMENT OF RENAL FUNCTION 1 BY EUGENE Y. BERGER, SAUL J. FARBER, AND DAVID P. EARLE, JR. WITH THE TECHNICAL ASSISTANCE OF ROSALYN JACKENTHAL (From the Third [New York University] Research Service, Goldwater Memorial Hospital, and the Department of Medicine, New York University College of Medicine, New York City) (Received for publication May 8, 1948) For any exogenous substance which is neither bladder rinses with water and air. The maximum rate metabolized, stored nor excreted otherwise than in of excretion of PAH by the tubules (TmPaH) was also measured in some of the experiments (3). Three or the urine, the rate of excretion must be equal to the more serial urine collection periods of 15 to 30 minutes rate of infusion under conditions where its plasma each were measured. level and volume of distribution are constant. Priming injections of inulin and PAH were given This steady state, as indicated by a constant plasma intravenously in amounts calculated to achieve plasma level, will be designated infusion equilibrium. levels of 5 to 20 and 2 to 3 mg. per cent respectively. The approximate volume of distribution for an average A simplified method for the measurement of normal subject was taken as 15 liters for inulin and 20 glomerular filtration rate and the effective renal liters for PAH. Priming injections of 2 grams of inulin plasma flow based upon the above principle has and 0.8 gram sodium p-aminohippurate were frequently been described elsewhere (1). In the application used and generally resulted in plasma levels of 10 to 15 of the principle, the rate of infusion, IV (where I and 2.5 to 3.0 mg.
    [Show full text]
  • Impaired Tubular Secretion of Organic Solutes in Acute Kidney Injury
    Kidney360 Publish Ahead of Print, published on June 24, 2020 as doi:10.34067/KID.0001632020 1 Impaired Tubular Secretion of Organic Solutes in Acute Kidney Injury Frank J. O’Brien1, Robert D. Mair2,3, Natalie S. Plummer2,3, Timothy W. Meyer2,3, *Scott M. Sutherland4, *Tammy L. Sirich2,3 1The Department of Medicine, Washington University, St. Louis, MO 2The Department of Medicine, Stanford University, Palo Alto, CA 3The Department of Medicine, VA Palo Alto Healthcare System, Palo Alto, CA 4The Department of Pediatrics, Lucile Packard Children’s Hospital, Stanford University, Palo Alto, CA *SMS and TLS are Joint Senior Authors Correspondence: Tammy L. Sirich Nephrology 111R Palo Alto VAHCS 3801 Miranda Ave. Palo Alto, CA 94304 [email protected] Copyright 2020 by American Society of Nephrology. 2 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 which undergo tubular secretion is reduced in proportion to the clearance of creatinine in humans with acute kidney injury (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 10 AKI patients and 17 control subjects. 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 which bind to plasma proteins. Results. Fractional clearance values for PAG, HIPP, IS, and PCS were greater than 1.0 in AKI patients as well as control subjects, indicating that these solutes were still secreted by the tubules of the injured kidneys.
    [Show full text]
  • Effects of Positive Pressure Ventilation on Intrarenal Blood Flow in Infant Primates
    Pediat. Res. 8: 792-796 (1974) Antidiuretic hormone intrarenal blood flow developmental physiology kidney intermittent positive pressure ventilation Effects of Positive Pressure Ventilation on Intrarenal Blood Flow in Infant Primates EDDIE S. MOO RE,(^^) MAURINA B. GALVEZ, JOHN B. PATON, DAVID E. FISHER, AND RICHARD E. BEHRMAN Department of Pediatvics, University of Illinois College of Medicine, Chicago, Illinois, USA Extract cortical flow rates in patients with acute failure. Horster and Thurau (9) found that superficial cortical and juxtamedullary Measurement of intrarenal distribution of renal blood flow nephrons in adult rats have different functional capacities. It by injection of radionuclides in 3-5-day-old infant monkeys can be speculated that the occurrence of decreased urine flow showed a preponderance of outer cortical over inner cortical might result from redistribution of blood to inner cortical " flow with flow rates of 4.23 and 2.54 ml/min/g, respectively. nephrons with possible greater reabsorptive capacity. The Intermit tent positive pressure ventilation (IPPV) causes a extent and character of overall renal function may therefore reversal of this flow pattern. The theoretical difference in be in part dependent upon intrarenal distribution as well as on nephron function in these two areas suggests that this reversal total renal blood flow. Although the studies of Jose et al. (1 1) in intrarenal flow induced by IPPV may have important demonstrated a low cortical flow and low total renal blood clinical implications. flow in infant puppies, few studies have been done in infants to measure the effect on intrarenal flow to various stimuli and Speculation how this would affect overall renal function.
    [Show full text]
  • Renal Function in Dogswith Pyometra
    Acta vet. scand. 1964, 5, 56-73. From the Department of Surgery and Department of Clinical Biochemistry, Royal Veterinary College, Stockholm, Sweden. RENAL FUNCTION IN DOGS WITH PYOMETRA 3. GLOMERULAR FILTRATION RATE, EFFECTIVE RENAL PLASMA FLOW, AND THE RELATION BETWEEN SOLUTE EXCRETION RATE AND MAXIMUM URINE OSMOLARITY DURING DEHYDRATION By Ake Asheim In bitches with pyometra (chronic purulent endometritis) the ability of the kidneys to excrete concentrated urine is impair­ ed with polyuria and polydipsia as a result (Asheim 1963 b). Since the limitation in concentrating ability cannot be ascribed to extrarenal causes (insufficiency of the hypothalamic-hypo­ physeal system, Asbeim 1963 a), it can fairly confidently be assumed to be of renal origin. Renal disease of whatever cause can lead to a reduction in the number of functioning nephrons. The residual functioning nephrons assume a greater excretory burden and because of this a greater osmotic load per nephron. This counterbalances the obligatory water resorption in the proximal tubules and results in so-called osmotic diuresis (Bricker et al. 1960, Kleeman et al. 1960). The osmotic diuresis is combined with a reduction of maximum urine osmolarity (max. Uosm) which is not affected by exogenous antidiuretic hormone (West & Rapoport 1950, Page & Reem 1952, Zak et al. 1954, Dorhout Mees 1959). As the osmotic load increases, max. Uosm gradually decreases until it approaches plasma osmolarity (Posm). Renal damage has been reported in bitches with pyometra (Bloom 1954). One has to take into account the possibility that the functioning renal mass can be reduced to such a degree to 57 give an osmotic diuresis which can explain the reduction of max.
    [Show full text]
  • Correction of Abnormal Renal Blood Flow Response to Angiotensin II by Converting Enzyme Inhibition in Essential Hypertensives
    Correction of abnormal renal blood flow response to angiotensin II by converting enzyme inhibition in essential hypertensives. J Redgrave, … , N K Hollenberg, G H Williams J Clin Invest. 1985;75(4):1285-1290. https://doi.org/10.1172/JCI111828. Research Article In 40-50% of patients with essential hypertension, a high sodium intake does not increase renal blood flow (RBF). These patients have been defined as nonmodulators because sodium intake does not modulate renal and adrenal responsiveness to angiotensin II (AII). To define the role of AII in mediating this altered responsiveness, we assessed the effect of a converting enzyme inhibitor (enalapril) on RBF and its responsiveness to AII in 25 patients with essential hypertension--10 modulators and 15 nonmodulators--and 9 normotensive controls. After 5 d of a 200-meq sodium intake, the nonmodulators did not increase RBF, whereas the normotensives (79 +/- 28 ml/min per 1.73 m2) and modulators (75 +/- 26 ml/min per 1.73 m2) did (P less than 0.025). Arterial blood pressure did not change in the modulators with the salt loading, whereas in the nonmodulators, blood pressure rose (P less than 0.004). After enalapril administration for 66 h, there was a significant difference (P less than 0.01, Fisher Exact Test) in the blood pressure response in the two hypertensive subgroups. In the modulators, there was no change; in the nonmodulators, despite the high salt diet, a blood pressure reduction occurred. In parallel, basal RBF and RBF responsiveness to AII were not changed after converting enzyme inhibition in the normotensive control (n = 9) or the hypertensive modulators (n = 10).
    [Show full text]
  • L3-Renal Clearance [PDF]
    At the end of this session, the students should be able to: Describe the concept of renal plasma clearance Use the formula for measuring renal clearance Use clearance principles for inulin, creatinine etc. for determination of GFR Explain why it is easier for a physician to use creatinine clearance Instead of Inulin for the estimation of GFR Describe glucose and urea clearance Explain why we use of PAH clearance for measuring renal blood flow Mind map Concept of clearance rate of glomerular filtration Clearance is the volume of plasma that is completely Assess severity of renal cleared of a substance each damage minute. Tubular secretion&reabsorption of renal clearance renal different substances. The important of important The Clearance Equation Clearance tests CX = (UX X V)/ PX endogenous where creatinine Urea Uric acid CX = Renal clearance (ml/min) UX X V = excretion rate of substance X exogenous U = Concentration of X in urine X Inulin Para amino Diodrast (di-iodo V = urine flow rate in ml/min hippuric acid pyridone acetic acid) Px= concentration of substance X in the plasma Measurement of glomerular Measurement of renal Measurement of renal filtration rate (GFR) plasma flow (RPF) blood flow (RBF) GFR is measured by the RPF can be estimated from RBF is calculated from clearance of a glomerular maker the clearance of an organic the RPF and hematocrit like Creatinine & Inulin . acid Para-aminohippuric acid (PAH) The formula used to calculate GFR or RPF is CX = (UX X V)/ PX X could be PAH , creatinine and inulin The formula used to calculate RBF is RBF= RPF \ 1-Hct Or RBF=RPF% \ 100-Hct Hematocrit is the fraction of blood volume that is occupied by red blood cells and 1-Hct or 100-Hct is the fraction of blood volume that is occupied only by plasma Criteria of a substance used Criteria of a substance used for for GFR measurement renal plasma flow measurement 1.freely filtered 1.freely filtered 2.not secreted by the tubular cells 2.rapidly and completely secreted by the renal tubular cells 3.not reabsorbed by the tubular cells.
    [Show full text]
  • Clinical Applications of a Kinetic Model of Hippurate Distribution and Renal Clearance
    CLINICAL APPLICATIONS OF A KINETIC MODEL OF HIPPURATE DISTRIBUTION AND RENAL CLEARANCE JosephA. DeGrazia,Paul0. Scheibe,PeterE.Jackson,ZoltanJ. Lucas, William R.Fair,JohnM. Vogel*, and LeonardJ. Blumin Stanford Medical Center, Stanford, California, A nalytical Development Associates Corporation, Cupertino, California, Community Hospital of Los Gatos-Saratoga, Los Gatos, California, USPHS Hospital, San Francisco, California, and Veterans Administration Hospital, San Francisco, California Measurements of effective renal plasma flow yield the basic parameters of renal physiology of and urine flow fractions have been obtained by interest to the clinician. the application of a new kinetic model of o-iodo Recent advances in nuclear medicine instrumenta hippurate distribution and renal clearance. tion and computing have made it possible to further Good agreement was obtained between these develop the radiohippurate method so that it is a estimates and those of comparable parameters quantitative measure of specific kidney functions obtained by conventional split-function tech (10—15). In general, these methods have used a niques using p-aminohippurate and inuliii@ Also, computer to aid in the adjustment of the variable examples have been presented of the use of this parameters of a mathematical description of hip test for the evaluation of patients suffering from purate turnover in the body to extract quantitative well-documented renal diseases. These uses have clinically useful data not usually obtained from the included serial testing in patients with major conventional renogram. renal artery occlusion, bilateral renal vein In this paper we report the first clinical applica thrombosis, obstruction due to stone, or trans tion of a new split-function renal test using an ex plant rejection.
    [Show full text]