Table Of ContentEXAMINATION OF KIDNEY FUNCTION
DEVELOPMENTS IN NEPHROLOGY
Also in this series:
Cheigh JS, Stenzel KH and Rubin AL: Manual of Clinical Nephrology of the
Rogosin Kidney Center.
1981 ISBN 90-247-2397-3
Nolph KD, ed.: Peritoneal Dialysis
1981 ISBN 90-247-2477-5
Gruskin AB and Norman ME, eds: Pediatric Nephrology
1981 ISBN 90-247-2514-3
Strauss J, ed.: Hypertension, Fluid-Electrolytes, and Tubulopathies in Pediatric
Nephrology
1982 ISBN 90-247-2633-6
Strauss J, ed.: Neonatal Kidney and Fluid-Electrolytes
1983 ISBN 0-89838-575-X
Examination of Kidney Function
o. SCHOCK
Institute for Clinical and Experimental Medicine, Prague
1984 MARTINUS NIJHOFF PUBLISHERS I.I...
a member of the KLUWER ACADEMIC PUBLISHERS GROUP
BOSTON / THE HAGUE / DORDRECHT / LANCASTER ....
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slovak Medical Press, Prague
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P.O.Box 322, 3300 AH Dordrecht, The Netherlands
Library of Congress Cataloging in Publication Data
Schuck, Ota.
Examination of kidney function.
(Developments in nephrology; v. 4)
Includes index.
1. Kidney function tests. I. Title. II. Series.
[DNLM: 1. Kidney function tests. 2. Kidney diseases - Physiopathology.
WI DE998EB v. 4/QY 175 S385e]
RC904.S338 616.6'1075 82-6402
ISBN-13: 978-94-010-8997-5 e-ISBN-13: 978-94-009-5660-5
DOl: 10.1007/978-94-009-5660-5
Book information
Joint edition published by: Martinus NijhoffPublishers Boston, USA and Avicenum,
Czechoslovak Medical Press, Prague
Copyright
© 1984 by Martinus NijhoffPublishers, Boston.
© Translation J.H. Cort
All rights reserved. No part of this pUblication may be reproduced, stored in a
retrieval system, or transmitted in any form of by any means, mechanical, photo
copying, recording, or otherwise, without the prior written permission of the
publishers,
Martinus Nijhoff Publishers, 190 Old Derby Street, Hingh~, MA 02043, U.S.A.
CONTENTS
Glomerular filtration 9
physiology and pathophysiology 11
methods of investigation. . . . 13
clearance of inulin . . . . . 13
clearance of endogenous creatinine 26
plasma concentration of endogenous creatinine 30
measurement of GFR by means of radionuclides 36
non-routine methods of measurement of GFR under special conditions 38
Urea ............ . 44
physiology and pathophysiology 45
methods of investigation. . . . 48
plasma urea concentration and blood urea nitrogen (BUN) . 48
the urea concentration in the urine 51
urinary urea excretion. . 52
renal urea clearance. . . 52
fractional urea excretion. 54
indications for investigation 56
Renal plasma and blood flow . 58
physiology and pathophysiology 58
methods of investigation. . 62
measurement of CPAH 66
renal extraction of P AH 68
calculation of the renal vascular resistance . 69
filtration fraction. . . . . . . . . . . . 70
measurement of ERPF on the basis of radionuclides 73
slope clearance of 131I-Hippuran . 74
the evaluation of separate ERPF 79
indications for investigation 80
Proteinuria . . . . . . . 85
physiology and pathophysiology 85
classification of proteinuria . . 91
methods of investigation. . . . 94
bedside and laboratory screening methods for proteinuria 94
the 24-hour protein excretion . . . . . . . . . . . . 95
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clearance of individual proteins and investigation of the selectivity of proteinuria 96
polymer clearances. . . 98
indications for investigation 98
Concentrating ability 108
physiology and pathophysiology 110
methods of investigation. . . . 113
urinary osmolarity after 36 hr restriction of water intake . 117
urinary osmolarity after 24 hr restriction of water intake . 118
urinary osmolarity after 16 hr restriction of water intake . 119
scatter of Uosm and specific gravity values over 24 hr under conditions of free fluid intake 119
urine osmolarity in the newly born and children . . 121
urine osmolarity after VP or dDAVP administration 121
tubular reabsorption of solute-free water 125
indications for investigation 127
Dilution of the urine . . . 133
physiology and pathophysiology 134
methods of investigation. . . . 142
simple ("bolus") water load . 145
maintained maximal water diuresis 149
induction of water diuresis by intravenous infusion of a hypotonic solution. 149
indications for investigation . . . . . . 150
Excretion of osmotically active solutes 157
physiology and pathophysiology . . . . 157
methods of investigation. . . . . . . . 159
excretion of osmotically active solutes per 24 hours 159
the osmolar clearance. . . . . . . . . . . . . 159
the fractional excretion of osmotically active substances 160
induced osmotic diuresis 161
indications for investigation 161
Excretion of potassium. . 164
physiology and pathophysiology 164
methods of investigation. . 170
urinary K concentration. 170
urinary K excretion. . . 170
the renal clearance of K 171
fractional K excretion. . 172
indications for investigation 176
Excretion of sodium . . . 180
physiology and pathophysiology 180
methods of investigation. . 185
urine Na concentration . 185
urinary excretion of Na . 186
the renal clearance of Na 189
fractional excretion of Na 189
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distal Na reabsorption . 191
indications for investigation 192
Excretion of chloride. . . 198
physiology and pathophysiology 198
methods of investigation. . . . 199
urinary excretion of Cl . . . 199
the renal Cl clearance and fractional excretion of Cl . 199
distal Cl reabsorption. . 200
indications for investigation . . . . . 200
Excretion of calcium and phosphate 202
physiology and pathophysiology 202
methods of investigation. . . . 206
urinary excretion of Ca . . . 206
urinary excretion on a normal diet 206
urinary excretion on a low Ca intake 207
the Ca/Cr ratio in fasting urine samples. 207
urinary Ca excretion after loading 208
serum Ca concentration . 208
the renal clearance of Ca . . . . . 209
fractional excretion of Ca . . . . . 209
urinary excretion and plasma concentration of phosphates 209
maximal tubular reabsorption of phosphates 209
indications for investigation 212
Acidifying capacity 218
physiology and pathophysiology 218
methods of investigation. . . . 223
spontaneous acidification . . 224
rapid amonium chloride test . 225
acidification test with arginine HCl . 227
several days with NH4Clloading. . 227
investigation of the renal bicarbonate threshold and the maximal tubular reabsorption of
bicarbonate . . . . . 227
indications for investigation 230
Glucose excretion 234
physiology and pathophysiology 234
methods of investigation. . . . 237
qualitative demonstration of glucose in the urine 237
glucose excretion ..... . 238
glucose "titration" and the Tma 238
indications for investigation 240
Uric acid excretion .... 243
physiology and pathophysiology 243
methods of investigation. . . . 246
urinary concentration of uric acid 246
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urinary excretion of uric acid 248
clearance of uric acid. . . . 248
fractional excretion of uric acid 249
indications for investigation 249
Amino acids excretion . . 252
physiology and pathophysiology 252
methods of investigation. . . . 256
demonstration of increased cystine excretion . 256
urinary excretion of alpha-amino-N 256
renal clearance of separate amino acids 257
fractional excretion of amino acids 257
indications for investigation 258
Index ......... . 263
8
GLOMERULAR FILTRATION
Historical remarks
Measurement of glomerular filtration rate (GFR) is one of the most important
methods of clinical investigation of kidney function.
From a historical point of view an important conceptual bridge between phy
siological studies and clinical practice - which culminated in the use of clearance
methods to investigate human renal function - was Rehberg's view in 1926 that
GFR could be measured in man. Rehberg was the first to make the correct as
sumption that GFR could be measured in man when using a marker substance
which would be readily filtrable at the glomerulus but not processed in any di
rection (other than in the direction of bulk flow) by the tubules. Using such
a substance, the amount excreted (UV) would be the same as the amount filtered.
If such a substance is easily filtrable at the glomerulus, its concentration in the
filtrate and in plasma (P) from venous blood should be almost identical.
This condition can be expressed by the following equation:
UV = GFR x P or
(1)
GFR= UV
P
Rehberg felt that creatinine fulfilled the above conditions because its concen
tration index (U IP) was the highest of any endogenous substances then known
(Fig. 1).
Present knowledge teaches us that creatinine, in man, is not excreted only by
glomerular filtration, but also by tubular secretion. The latter is more significant
with administration of an exogenous creatinine load. Nevertheless, Rehberg's
work on the theoretical basis of GFR measurement in man, and even his choice
of creatinine as the marker substance, were historical milestones for functional
investigation of the kidneys in clinical medicine.
Richards, Westphall and Bott (1934) and Shannon and Smith (1935) devoted
great energy to finding a better marker substance to fulfill Rehberg's conditions.
Both groups arrived at the polysaccharide inulin as the ideal marker.
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Fig. 1: Concentration index of various
u
substances excreted by the human kidney.
p
creatinine
Measurement of inulin clearance became the most precise estimate of GFR
in man and experimental animals. Unfortunately, this measurement is neither
simple nor satisfactory for routine clinical practice, and further marker substances
were still sought after. Each new marker was compared to inulin which had become
the reference Standard.
Out of the complex series of studies, the clearance of endogenous creatinine was
finally settled on as the most appropriate for routine clinical investigation.
The relation between inulin and endogenous creatinine clearances in healthy
subjects and in patients with renal disease has occupied the attention of many la
boratories.
Many complications arose from the biochemical problems of determining "true"
levels of endogenous creatinine versus the so-called "Jaffe positive chromogen".
At present, these analytical procedures have been so unified and solved that
endogenous creatinine clearance (Ccr) has become the clinical reference method
of choice, even if it is not "exactly" the same as "true" GFR.
Since the quantitative urine collection is usually difficult, the glomerular function
in routine clinical practice is usually assessed semi quantitatively by measurement
of the plasma creatinine concentration alone.
In recent years there have been attempts to simplify. the measurement of GFR
using radionuclides. A number of substances have been suggested. Good agre
ement has been observed between GFR and the clearance (evaluated on the basis
of the slope clearance technique) of the following substances: 51Cr-EDTA, 1311-
lothalamate and 99mTc-DTPA.
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