RENAL FUNCTION TESTS
RENAL FUNCTION TESTS
Muhammad Saeed, Ph.D
OBJECTIVES
To detect possible renal damage and
assessment of its severity.
To observe the progress of renal disease
To monitor the safe and effective use of drugs
which are excreted in the urine
Tests usually included in the list;
C Urine examination
C Tests of excretory functions
C Creatinine clearance
C Urinary acidification tests
C Urinary excretion of sodium and potassium
C Estimation of BUN and serum creatinine
levels
URINE EXAMINATION
Urine examination is an extremely valuable and
most easily performed test for the evaluation of
renal functions.
It includes physical or macroscopic examination,
chemical examination and microscopic
examination of the sediment. It has been
discussed in detail in a separate chapter.
TESTS OF EXCRETORY FUNCTIONS
If the clinical findings or simple urine
examination indicate that renal damage is
present, renal function can be assessed by tests
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INV-05
of excretory function. Following tests can be
performed for this purpose;
‚ Urine concentration test
‚ Vasopressin test
‚ Urine dilution or water load test
‚ Dye excretion tests
URINE CONCENTRATION TEST
The ability of the kidney to concentrate urine is
a test of tubular function that can be carried out
readily with only minor inconvenience to the
patient. This test requires a water deprivation for
14 hrs and has replaced the previous 24 hrs
water deprivation test. The test should not be
performed on a dehydrated patient.
PROCEDURE
The patient eats an early supper and is allowed
no food or water after 6 p.m. on the night
preceding the test. Discard any urine voided
during the night.
On the test day, the first specimen is voided at
7.00 a.m., the bladder is emptied completely
and the specimen is discarded.
A second specimen is collected at 8 a.m., 14 hrs
after the commencement of the test, and the
osmolality or specific gravity is measured. If the
osmolality exceeds 850 m osm/kg or the specific
gravity is > 1.022, the patient has adequate
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renal concentration power and the test is over.
If the values are < 850 m osm/kg or 1.022, for
osmolality and specific gravity respectively, a
urine sample is collected at 9 a.m. and assayed.
The renal concentrating ability is impaired if
neither urine sample reached an osmolality of
850 m osm/kg or a specific gravity of 1.022.
Normal values may be as higher as 1350 m
osm/kg or specific gravity of 1.032. If the
concentrating ability should fail, the specific
gravity would be 1.010 and osmolality close to
300 m osm/kg.
VASOPRESSIN TEST
This is more pleasant for the patient than full
water deprivation, and depends only on renal
tubular function.
METHOD
The patient has nothing to drink after 6 p.m. At
8 p.m. five units of vasopressin tannate is
injected subcutaneously. All urine samples are
collected separately until 9 a.m. the next
morning.
INTERPRETATION
Satisfactory concentration is shown by at least
one sample having a specific gravity above
1.020, or an osmolality above 800 m osm/kg.
The test may be combined with measurements
of plasma osmolality. The urine/plasma
osmolality ratio should reach 3 and values less
than 2 are abnormal.
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RENAL FUNCTION TESTS
If this test or the water deprivation test gives a
normal result, and there is no protein in the
urine, then it is unlikely that standard clearance
tests will show functional damage in diffuse
renal disease. This test will often detect impaired
function when creatinine clearance is normal, as
in hypertension or potassium deficiency.
URINE DILUTION (WATER LOAD) TEST
This test is very simple, but because it is less
sensitive than the water deprivation test as test
of renal damage its use is not often required.
METHOD
After an overnight fast the patient (who is not
allowed to smoke) empties his bladder
completely and is given 1000 ml of water to
drink. Urine specimens are collected for the next
4 hours, the patient emptying bladder
completely on each occasion.
INTERPRETATION
Unless there is renal functional impairment, the
patient will excrete at least 700 ml of urine in the
4 hours, and at least one specimen will have a
specific gravity less than 1.004. Kidneys which
are severely damaged cannot excrete a urine of
lower specific gravity than 1.010 or a volume
above 400 ml in this time. There is a delayed
diuresis.
Abnormal results are also found if there is
delayed water absorption or adrenal cortical
hypofunction. The test should not be done if
there is oedema or renal failure; water
intoxication may result.
RENAL FUNCTION TESTS
DYE EXCRETION TESTS
Many dyes are excreted by the kidneys, and
measurement of their concentration in the urine
after parenteral injection can be used as a
measure of renal function. Phenol-
sulphonphthalein (phenol red) is filtered by the
glomeruli and secreted by the tubules. Its
excretion essentially tests for renal plasma flow
and is therefore impaired early in conditions
such as heart failure. After intramuscular or
intravenous injection of 6 mg of dye to a normal
subject, 40-60 percent of the dose will be
excreted in the first hour, and another 20-25
percent in the second hour; less than 50 percent
excreted over two hours is abnormal.
Indigo-carmine is sometimes used in surgical
practice. During cystoscopy both ureteric orifices
may be observed, and after intravenous
injection of 100 mg dye, colour should be seen
issuing from both ureters, in about equal
concentration, in 15 minutes. Maximum
excretion is normally reached in 45 minutes.
CREATININE CLEARANCE TEST
The value of this test is that of a roughly
quantitative measure of glomerular damage
when simpler tests have already demonstrated
renal impairment. Due to lack of sensitivity it is
not considered the first line test for the diagnosis
of renal function impairment. The creatinine
clearance may be normal when early renal
damage has been demonstrated by urine
concentration test and by the presence of
proteinuria as in hypertension. This test may be
done over two separate hourly periods or over 4
hours, but a 24 hour period for measurement of
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33
endogenous creatinine clearance is
recommended. The results are independent of
the rate of urine flow.
METHOD
A careful and accurate 24 hour collection of
urine is made. At some time during the day (but
not within 1-3 hours after a large meal) a blood
sample is taken for plasma creatinine analysis;
this and the whole 24 hours urinary collection
are sent to the laboratory.
Calculation of creatinine clearance is made with
the help of formula (U x V)/P x 1.73/A
where
U = Urine creatinine concentration
P = Plasma creatinine concentration
V = Urine flow in ml/min
A = Body surface area in m2 and
1.73 is the standard body surface area
Body surface area can be measured with the
help of height and weight charts or with the help
of following formula.
log A = 0.425 log W + 0.725 log H - 2.144
where
A = Body surface area in m2
W = Weight in Kg
H = Height in cm
INTERPRETATION
Endogenous creatinine clearance is a rough
measure of the glomerular filtration rate and is
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normally 100-130 ml/min in an adult of normal
size. Correction is necessary for surface area in
children, or in adults of abnormal build.
Values below 90 ml/min (corrected to normal
surface area) are indicative of diminished
glomerular filtration rate. The test has particular
value in the general assessment of renal
function in cases when plasma analyses are
invalid, such as after dialysis, or when the BUN
(but not the plasma creatinine) has been
lowered by a low protein diet.
Errors in 24 hours urine collection lead to the
incorrect values for creatinine clearance. The
formula of Cock Croft and Gaut is a very helpful
tool to avoid this complication.
According to this formula
Creatinine clearance = 140-Age x Weight (Kg)
Plasma Creatinine x 72
For females the estimated GFR is 15% less than
the calculation because of less muscle mass.
URINARY ACIDIFICATION TEST
This procedure tests the ability of the renal
tubules to form an acidic urine and to excrete
ammonia. It is useful if there is doubt whether a
patient's acidosis (confirmed by plasma
analyses) is due to a pre-renal cause, or to
kidney damage as in renal tubular acidosis.
METHOD
The patient fasts from midnight until the
conclusion of the test, zero time. The patient
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RENAL FUNCTION TESTS
empties his bladder completely. The urine is
collected. The patient takes 0.1 g (1.9 m mol) of
ammonium chloride/kg body weight and drinks
a liter of water. A standard dose of 5 g is
sometimes used. In children the dose should be
proportional to the body surface area.
At 2 hours, 4 hours, and 6 hours; complete urine
specimens are collected.
INTERPRETATION
In a normal subject the urine will be acidified to
pH 5.3 or less, and will contain more than 1.5 m
mol of ammonia per hour, in at least one of the
specimens. If there is marked damage to the
renal acidifying power, the pH of the later
specimens of urine will be unaltered from that of
the resting specimen, and less than 0.5 m mol of
ammonia per hour will be excreted.
The pH results are more significant than the
ammonia results, as 3 days are needed for full
development of extra ammonium ion excretion.
URINARY EXCRETION OF SODIUM AND
POTASSIUM
SODIUM EXCRETION
The kidney normally excretes sodium and can
conserve sodium very efficiently if dietary
sodium is reduced. In chronic renal failure,
however, the capacity of the kidney to adapt to
changes in sodium intake is reduced. In most
patients with chronic renal failure it is possible to
maintain adequate sodium balance provided
large changes in sodium intake are avoided.
When the ability of the diseased kidneys, to
RENAL FUNCTION TESTS
adapt to changes in sodium intake is exceeded,
there is a tendency to retain sodium and water
and oedema develops when dietary sodium is
increased. On the other hand, if dietary sodium
is restricted, the diseased kidneys may fail to
conserve sodium and water, and the
consequent depletion may, in turn, reduce the
GFR even further.
Occasionally, in chronic pyelonephritis or other
disorders affecting primarily the renal tubules,
large amounts of sodium are lost in the urine
and severe sodium depletion can occur.
It is possible to test the ability of the kidney to
conserve sodium by giving a diet containing 20
m mol sodium/day. Normally the urinary sodium
excretion should fall to the amount present in
the diet within a week. This test should always
be monitored with great care by daily
measurement of plasma [sodium] and [urea],
since severe sodium depletion may be induced.
Measurement of urinary sodium should form part
of the overall assessment of fluid and electrolyte
balance in patients on fluid replacement therapy.
It is important to collect all the urine passed. In
these patients it is also important to assess all
other losses of fluid and electrolytes, and relate
losses to the patient's intake, dietary and
parenteral.
POTASSIUM EXCRETION
This is largely independent of GFR since
potassium is completely reabsorbed from the
glomerular filtrate in the proximal tubules and
secreted by the distal tubules. The rate of
secretion of potassium is influenced by the
SURGERY-INVESTIGATIONS
35
transtubular potential and by the tubular cell
[potassium]. It is usually maintained adequately
provided the urine flow rate is greater than one
liter per day. Retention of potassium tends to
occur late in the progress of renal disease, when
oliguria and anuria supervene. However, in
patients with oliguria due to acute or chronic
renal failure, hyperkalemia and potassium
retention can develop rapidly. Dangerous
hyperkalemia can follow the ingestion of
potassium containing foods.
Excessive renal losses of potassium only rarely
occur in chronic renal disease. However, the
sodium depletion, which sometimes occurs in
renal disease, may be associated with
secondary aldosteronism. This in turn, causes
excessive loss of potassium. Acid-base
disturbances markedly affect renal output of
potassium. Excessive losses occur particularly
when there is a metabolic alkalosis, since the
kidney is unable to conserve potassium
efficiently in the presence of an alkalosis. Some
of the primary tubular disorders are also
associated with excessive losses of potassium,
and treatment with diuretics commonly causes
potassium depletion.
Measurement of urinary potassium output may
provide valuable data in patients suspected of
having abnormal losses. If dietary potassium is
reduced to 20 m mol/day, urinary output should
fall to this value within one week (occasionally
this takes two weeks) in healthy individuals. The
persistence of a relatively high urinary
potassium output in the presence of
hypokalemia strongly suggests that the kidney is
not able to conserve potassium adequately.
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ESTIMATION OF BLOOD UREA NITROGEN
(BUN) & SERUM CREATININE
There is no plasma constituent whose
concentration depends solely on the functional
state of the kidneys. In renal failure all non-
protein nitrogen constituents of the plasma are
retained. Blood urea Nitrogen estimations are
frequently performed as a test of renal function,
but the causes of a raised BUN are many such
as;
C Haemorrhage in the gut or body tissues
C Severe infections
C Burns
C Muscle injury
C High gluco corticoid dosage
C Tetracycline therapy (with the exception of
doxycycline)
It is not possible to detect renal damage by a
raised BUN until renal function has fallen by
about 50 percent as measured by the creatinine
clearance test. Analyses of BUN (or serum
creatinine) can be used as a quantitative
measure of known glomerular damage. The
estimation is most useful for the assessment of
the severity and progress of renal failure in;
C Acute tubular necrosis
C Acute glomerulonephritis
C Chronic renal disease
C Post-renal obstruction
Decrease in BUN level may be caused by;
C Low protein diet
C Liver damage
C Dialysis
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RENAL FUNCTION TESTS
Under these conditions plasma creatinine
clearance (or even plasma creatinine) will be a
true measure of the renal damage because
endogenous creatinine production remains
relatively constant.
Other plasma analyses, such as measurement
of uric acid, electrolytes and acid base state, or
of proteins, although valuable and often
necessary in the assessment of known renal
disease, show alterations in a wide variety of
other disorders.
Normal Plasma values of BUN and creatinine
are as follows;
BUN = 8-25 mg/dl
Creatinine = 0.6-1.6 mg/dl
CHOICE OF RENAL FUNCTION
Examination of the urine is the most important
initial test for suspected renal damage,
particularly glomerular diseases. Search must
be made for protein, erythrocytes and casts. The
urine concentration test (or vasopressin test) is
sensitive. It is possibly the most useful single
test for confirming the presence of renal tubular
impairment. The creatinine clearance is
quantitative for glomerular impairment and
needs rarely be done unless simpler tests are
abnormal. The estimation of plasma urea or
creatinine should be done as a guide to
progress and prognosis if there is severe renal
damage or obstruction.
RENAL FUNCTION WITH INCREASING AGE
There is a gradual decrease in all aspects of
RENAL FUNCTION TESTS
renal function after 35 years of age. This
appears to be due to involution, but may be
aggravated by renal vascular degeneration. The
most clinically significant change is the gradual
reduction in GFR which, when accompanied by
a progressive decrease in muscle mass, may
result in very little change in the serum
creatinine concentration. If the lowered GFR is
not recognized, elderly patients are at grave risk
from the accumulation and consequent toxicity
of drugs normally excreted in the urine (such as
digitalis, aminoglycoside antibiotics).
REFERENCES
1. Ruddy, M. C. and Stenzel, K. H. Disorders of
water, sodium and potassium metabolism. In
Cheigh, J.S. et al., (eds); Manual of clinical
Nephrology. Mattinus Nighoff, 1981.
2. Tobias: G.J et al., Endogenous creatinine
clearance. N. Engl. J. Med; 266.317. 1962
3. Vatrin; H. Renal function; M echanism s
preserving fluid and solute balance in
Health. Boston, little. Brown and Co. 1973.
4. Ward, P.C. Renal dysfunction 1; Urea and
Creatinine Postgrad. Med; 69(5).93; 1981.
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5. Barlow L. K. et al., Volatile and osmometry
continued. clin chem 22.1230. 1976.
6. Camara A. A., et al., The twenty four hourly
endogenous creatinine clearance as a
clinical measure of the functional state of
the kidneys J. Lab. Clin. med. 37.743; 1951.
7. Duarte, C.G; Glomerular filtration rate and
renal plasma flow. In renal function tests,
c linic a l la b o ra t ory p ro c e d u re s a nd
Diagnosis. Boston, little, Brown and Co. 1980
8. Greenhil, A, and Grusk, F.C: Laboratory
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9. Mac Donald, N.F. Sodium and Potassium
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