Renal Function Tests

MN  Chatterjea; Rajinder  Chawla

Part One

1Organ Function Tests2

Renal Function TestsChapter 1

INTRODUCTION

The body has a considerable factor of safety in renal as well as hepatic tissues. One healthy normal kidney can do the work of two, and if all other organs are functioning properly, less than a whole kidney can suffice.

On the other hand, there are certain extrarenal factors which can interfere with kidney function, specially circulatory disturbances. Hence, methods that appraise the functional capacity of the kidneys are very important. Such tests have been devised and are available, but it is stressed that no single test can measure all the kidney functions. Consequently, more than one test is indicated to assess the kidney function.

PRELIMINARY INVESTIGATIONS

Assessment of renal function begins with the appreciation of:

Patient's history: A proper history taking is important, particularly in respect of oliguria, polyuria, nocturia, ratio of frequency of urination in day time and night time. Appearance of oedema is important.
Physical examination: This is followed by side room analysis of the urine specially for presence/or absence of albumin, and microscopic examination of urinary deposits specially for pus cells, RB cells and casts.
Biochemical parameters: Certain biochemical parameters also help in assessing kidney function.

A stepwise increase in three nitrogenous constituents of blood is believed to reflect a deteriorating kidney function. Some authorities claim that serum uric acid normally rises first, followed by urea and finally increase in creatinine. By determining all the above three parameters a rough estimate of kidney function can be made. However, other causes of uric acid rise should be kept in mind.

Other biochemical parameters which may help are determination of total plasma proteins, and albumin and globulins and total cholesterol. In nephrosis there is marked fall in albumin and rise in serum cholesterol level.

PHYSIOLOGICAL ASPECT

Main functions of the kidney are:

To get rid the body of waste products of metabolism,
To get rid of foreign and non-endogenous substances,
To maintain salt and water balance, and
To maintain acid-base balance of the body.

A. Glomerular Function

The glomeruli act as “filters”, and the fluid which passes from the blood in the glomerular capillaries into Bowman's capsule is of the same composition of protein-free plasma.

The effective filtration pressure which forces fluid through the filters is the result of:

the blood pressure in the glomerular capillaries and4
the opposing osmotic pressure of plasma proteins, renal interstitial pressure and intratubular pressure. Thus,

•	Capillary pressure	=75 mmHg
•	Osmotic pressure of plasma proteins	=30 mmHg
•	Renal interstitial pressure	=10 mmHg
•	Renal intratubular pressure	=10 mmHg

Hence, net effective filtration pressure

= 75 −(3 + 10 + 10)

= 25 mmHg

Rate of filtration is influenced by:

Variations in BP in glomerular capillary,
Concentration of plasma proteins,
Factors altering intratubular pressure, viz.,
1. rise with ureteral obstruction;
2. during osmotic diuresis.
State of blood vessels.

If the efferent glomerular arteriole is constricted, the pressure in the glomerulus rises and the effective filtration pressure is increased. On the other hand, if the afferent glomerular arteriole is constricted, the filtration pressure is reduced.

The volume of glomerular filtrate formed depends on:

the number of glomeruli functioning at a time;
the volume of blood passing through the glomeruli per minute; and
the effective glomerular filtration pressure.

Under normal circumstances, about 700 ml of plasma (contained in 1300 ml of blood or approximately 25% of entire cardiac output at rest) flow through the kidneys per minute and 120 ml of fluid are filtered into Bowman's capsule. The volume of the filtrate is reduced in extrarenal conditions, such as dehydration, oligaemic shock and cardiac failure which diminish the volume of blood passing through the glomeruli, or lower the glomerular filtration pressure, and when there is constriction of the afferent glomerular arterioles or, changes in the glomeruli such as occur in glomerulonephritis. If the volume of glomerular filtrate is lowered below a certain point, the kidneys are unable to eliminate waste products which accumulate in blood.

B. Tubular Function

Whereas the glomerular cells act only as a passive semipermeable membrane, the tubular epithelial cells are a highly specialised tissue able to reabsorb selectively some substances and secrete others. About 170 litres of water are filtered through the glomeruli in 24 hours, and only 1.5 litres is excreted in the urine. Thus, nearly 99% of the glomerular filtrate is reabsorbed in the tubules.

Glucose is present in the glomerular filtrate in the same concentration as in the blood but practically none is excreted normally in health in detectable amount in urine and the tubules reabsorb about 170 gm/day. At an arterial plasma level of 100 mg/100 ml and a GFR of 120 ml/minute, approximately 120 mg of glucose are delivered in the glomerular filtrate in each minute. Maximum rate at which glucose can be reabsorbed is about 350 mg/minute (Tm G), which is an ‘active’ process. About 50 grams of urea are filtered through the glomeruli in 24 hours, but only 30 grams are excreted in the urine, this is a passive diffusion.

Certain substances foreign to the body, e.g. diodrast, para-aminohippuric acid (PAH) and phenol red are:

filtered through the glomeruli, and in addition are
secreted by the tubules. Thus, the amount of these substances excreted per minute in the urine is greater than that filtered through the glomeruli per minute. At low blood levels, the tubular capacity for excreting these compounds is so great that plasma passing through the kidneys is almost completely cleared of them.

Another group of substances, e.g. inulin, thiosulphate, and mannitol are eliminated exclusively by the glomeruli and are neither reabsorbed nor secreted by the tubules. Hence, amount of these substances excreted per minute in the urine is the same as the amount filtered 5through the glomeruli per minute, thus they give the glomerular filtration rate (GFR).

CLASSIFICATION

Based on the above functions, the renal function tests can be classified as follows:

Tests Based on Glomerular Filtration
1. Urea clearance test.
2. Endogenous creatinine clearance test.
3. Inulin clearance test.
4. Radio-isotopes in measurement of GFR.
  1. ⁵¹Cr–EDTA clearance.
  2. ^99mTc–DTPA clearance.
Tests to Measure Renal Plasma Flow (RPF)
1. Para-amino hippurate (PAH) test.
2. Measurement of ERPF by radioisotope-¹³¹I-labelled hippuran.
3. Filtration fraction (FF).
Tests Based on Tubular Function
1. Concentration and dilution tests.
2. 15 minute–PSP excretion test.
3. Measurement of tubular secretory mass.
Certain Miscellaneous Tests

These tests can determine size, shape, asymmetry, obstruction, tumour, infarct, etc.

A. GLOMERULAR FILTRATION TESTS

These are used to examine for impairment of glomerular filtration. Recently, ⁵¹Cr-EDTA and ^99mTc-DTPA clearance tests have been described.

What is meant by clearance test?

As a means of expressing quantitatively the rate of excretion of a given substance by the kidney, its “clearance” is frequently measured. This is defined as, “a volume of blood or plasma which contains the amount of the substance which is excreted in the urine in one minute”, or alternatively, “the clearance of a substance may be defined as that volume of blood or plasma cleared of the amount of the substance found in one minute's excretion of urine”.

I. Urea Clearance Test

Ambard was the first to study the concentration of urea in blood and relate it to the rate of excretion in the urine, and “Ambard's coefficient” was, for a while, the subject of much clinical study. At present, the blood/plasma urea clearance test of Van Slyke is widely used.

Blood urea clearance is an expression of the number of ml of blood/plasma which are compeletely cleared of urea by the kidney per minute. As a matter of fact, the plasma is not completely cleared of urea. Only about 10% of the urea is removed. Consequently, 750 ml of plasma pass through the kidney per minute and 10% of the urea is removed, this is equivalent to completely clearing 75 ml of plasma per minute.

A. Maximum Clearance

If the urine volume exceeds 2 ml/minute, the rate of urea elimination is at a maximum and is directly proportional to the concentration of urea in the blood. Thus, provided the blood urea remains unchanged, urea is excreted at the same rate whether the urinary output is 4 ml or 8 ml/minute.

Volume of blood cleared of urea per minute can be calculated from the formula,

where

U=Concentration of urea in urine (in mg/100 ml)

V=Volume of urine in ml/minute

B=The concentration of urea in blood (in mg/100 ml)

Substituting average values, the number of ml of blood cleared of urea per minute =

A urea clearance of 75 does not mean that 75 ml of blood have passed through the kidneys in one minute and were completely cleared of 6urea. It means that the amount of urea excreted in the urine in one minute is equal to the amount found in 75 ml of blood. The clearance which occurs when the urinary volume exceeds 2 ml/minute is termed as Maximum urea clearance (C_m) and average normal value is 75.

B. Standard Clearance

When the urinary volume is less than 2 ml/minute, the rate of urea elimination is reduced, because relatively more urea is reabsorbed in the tubules, and is proportional to the square root of the urinary volume. Such clearance is termed as standard clearance of urea (C_s) and average normal value is 54.

Note

Provided no prerenal factors are temporarily reducing the clearance of urea, the volume of blood cleared of urea per minute is an index of renal function.

If a larger volume than normal is cleared/minute renal function is satisfactory.
If a smaller volume is cleared, renal function is impaired.

Expression As %

Sometimes the result of a urea clearance test is expressed as a % of the normal maximum or of the normal standard urea clearance depending on whether the urinary output is greater or lesser than 2 ml/minute.

Expressed as % of normal

Relation with Body Surface

The urea clearance is proportional to the surface area of the body and if the result is to be expressed as a % of normal, a correction must be made in the case of children and those of abnormal stature. The C_m is directly proportional to the body surface and if any correction is required the result should be multiplied by 1.73/BS, where BS = the patient's body surface derived from the height and weight. In the case of C_s', the correction factor is

Procedure

The test should be performed between breakfast and lunch, as excretion is more uniform during this time.

The patient, who is kept at rest throughout the test, is given a light breakfast and 2 to 3 glasses of water.
The bladder is emptied and the urine is discarded, the exact time of urination is noted.
One hour later, urine is collected and a specimen of blood is withdrawn for determining urea content.
A second specimen of urine is obtained at the end of another hour.

The volume of each specimen of urine is measured accurately and the concentration of urea in the specimen of blood and urine is determined. The average value of the two specimens of urine is used for assessing the quantity and urea content of urine.

Interpretation

Urea clearance of 70% or more of average normal function indicates that the kidneys are excreting satisfactorily. Values between 40 and 70% indicates mild impairment, between 20 and 40% moderate impairment and below 20% indicates severe impairment of renal function.

In acute renal failure, the urea clearance C_m or C_s, is lowered, usually less than half the normal and increases again with clinical improvement.7
In chronic nephritis the urea clearance falls progressively and reaches a value half or less of the normal before the blood urea concentration begins to rise. With values below 20% of normal, prognosis is bad, the survival time rarely exceeds two years and death occurs within a year in more than 50% cases.
Terminal uraemia is invariably found when the urea clearance falls to about 5% of the normal values.
In nephrotic syndrome the urea clearance is usually normal until the onset of renal insufficiency sets in and produces the same changes as in chronic nephritis.
In benign hypertension a normal urea clearance is usually maintained indefinitely except in few cases which assume a terminal malignant phase when it falls rapidly.

Note

A very low protein diet can lead to low clearance value even in normal persons and in patients with mild renal disease.

II. Endogenous Creatinine Clearance Test

At normal levels of creatinine, this metabolite is filtered at the glomerulus but neither secreted nor reabsorbed by the tubules. Hence, its clearance gives the GFR. This is a convenient method for estimation of GFR since

it is a normal metabolite in the body;
it does not require the intravenous admini-stration of any test material; and
estimation of creatinine is simple. Measure-ment of 24 hour excretion of endogenous creatinine is convenient. This longer collection period minimizes the timing error.

Procedure

An accurate 24-hour urine specimen is collected ending at 7 a.m. and its total volume is measured.
Collect a blood sample for serum creatinine determination.
Estimate the serum and urinary creatinine concentration.

Result

where,

U=Urine creatinine concentration in mg/dl

P=Serum creatinine in mg/dl

V=Volume of urine in ml/minute

Normal values for creatinine clearance varies from 95 to 105 ml/minute.

III. Inulin Clearance Test

Inulin, a homopolysaccharide, polymer of fructose is an ideal substance as;

it is not metabolized in the body;
following IV administration, it is excreted entirely through glomerular filtration, being neither excreted nor reabsorbed by renal tubules. Hence, the number of ml of plasma which is cleared of Inulin in one minute is equivalent to the volume of glomerular filtrate formed in one minute.

Procedure

Preferably performed in the morning. Patient should be hospitalized overnight and kept reclining during the test.
A light breakfast is given consisting of half glass milk, one slice toast can be given at 7.30 a.m.
At 8 a.m. 10 gm of inulin dissolved in 100 ml of saline, at body temperature, is injected IV at a rate of 10 ml per minute.
One hour after (9 a.m.) the injection, the bladder is emptied and this urine is discarded.
Note the time and collect urine one and two hours after. Volume of urine is measured and analyzed for inulin content.
At the midpoint of each collection of urine, 30 and 90 minutes after the initial emptying of bladder, 10 to 15 ml of blood is withdrawn (in oxalated bottle), plasma is separated and analyzed for inulin concentration.

Calculation and Result

Values obtained from two samples of blood are averaged.

where,

U=mg of inulin/100 ml of urine

V=ml of urine/minute

P=mg of inulin/dl of plasma (average of two samples)

Normal average: Inulin clearance in an adult (1.73 sqm) = 125 ml of plasma cleared of inulin/minute. Range = 100 to 150 ml.

Note

To promote a free flow of urine, one glass of water is given at 06.30 a.m. and repeated every half an hour until the test is completed. This step may be eliminated if administration of fluid is contraindicated.
Inulin clearance test is definitely superior for determination of GFR but requires tedious and intricate chemical procedure for determination.

IV. Radioisotopes in Measurement of GFR

Clinical advances in management techniques that halt or retard the progression of renal impairment requires an accurate and practical method for monitoring a patient's renal function.

Endogenous creatinine clearance test described above tends to overestimate GFR as renal failure evolves; whereas inulin clearance measurements although accurate are too cumbersome to use routinely.

The above limitations have stimulated the discovery and use of several radioisotopes with renal clearance characteristics that make them useful in assessing GFR and RPF on patients with renal insufficiency.

Methods

Measurement of GFR, either on the basis of urinary clearance or plasma clearance of the isotope can be reliably undertaken using the following methods:

⁵¹Cr-Ethylene diamine tetra-acetic acid (⁵¹Cr-EDTA clearance)
^99mTc diethylene triamine Penta acetic acid (DTPA)- for split renal function

To ensure accuracy in the measurement of GFR by urinary clearance of radionucleotide, it is essential that:

renal tubular secretion or reabsorption does not contribute to the elimination of the compound;
plasma protein binding of the isotope is negligible; and
patients completely empty their urinary bladder.

Plasma clearance of a radionucleotide measures GFR reliably only if non-renal clearance routes are negligible.

1. ⁵¹Cr-EDTA Clearance

Currently simplified single injection method for determination of ⁵¹Cr-EDTA plasma clearance is widely used, for routine assessment of glomerular filtration rate (GFR) in adults as well as in children.

It is particularly convenient in children where it is not easy to collect 24 hour urine sample. It has been used for children younger than one year.

A dose of 4.5 μci (0.17 MBq)/kg body weight of ⁵¹Cr-EDTA is injected IV. Capillary blood samples are drawn at 5, 15, 60, 90 and 120 minutes after the injection and simultaneously the haematocrit (hct) is determined. The radioactivity is calculated as measured activity in 0.2 ml capillary blood/1-hct. The ⁵¹Cr-EDTA plasma clearance is determined as the ratio between the injected amount of the ‘tracer’ (Q_o) and the total area under the plasma activity curve c (t) which is resoluted into two mono-exponential functions (Fig. 1.1).

The plasma clearance (cl) is then calculated as,

Figs 1.1A and B: ⁵¹Cr-EDTA activity C(t) in capillary plasma samples. Disappearance of ⁵¹Cr-EDTA. In curve (A) C₁ and C₂ are intercepts (monoexponential functions) and b₁ and b₂ rate constants. In (B) the disappearance curve is indicated by the solid line while the broken line shows the monoexponential curve that is used in estimating ⁵¹Cr-EDTA clearance from a single sample drawn

To determine plasma clearance from a single sample the mean transit time and extracellular fluid volume are estimated, and then cl = Ecv/t gives the clearance value.

2. ^99mTc-DTPA Clearance

This technique measures the split renal function. Separate estimation of GFR within the right and left kidneys is referred to as the split renal function technique

Gate's technique

Basis: This test is based on the fact that the fractional renal uptake of intravenously administered ^99mTc-DTPA, within 2 to 3 minutes after radio-tracer arrival within the kidneys, is proportional to the GFR.

Thus, with this technique it is possible to determine both split renal function and total GFR.

The actual test is less time consuming and does not take more than 5 to 10 minutes.

B. TESTS FOR RENAL BLOOD FLOW

1. Measurement of Renal Plasma Flow (RPF)

Para-aminohippurate (PAH) is filtered at the glomeruli and secreted by the tubules. At low blood concentrations (2 mg or less/100 ml) of plasma, PAH is removed completely during a single circulation of the blood through the kidneys. Tubular capacity for excreting PAH of low blood levels is great. Thus, the amount of PAH in the urine becomes a measure for the value of plasma cleared of PAH in a unit time, i.e. PAH clearance at low blood levels measures renal plasma flow (RPF).

RPF (for a surface area of 1.73 sqm) = 574 ml/minute.

2. Mesurement of Effective Renal Plasma Flow (ERPF) by Radioisotope

Though PAH method is satisfactory but not very accurate. ERPF is a measurement of tubular secretory function combined with GFR. Selection of a suitable test substance requires that

the compound be minimally protein-bound to provide for glomerular filtration; and
the non-filtered residual drug exiting the glomerulus in the efferent arteriole be completely secreted into the lumen of the tubule such that renal venous blood is fully cleared of the test substance.

It is to be noted that a small fraction of renal blood flow (approximately 8%) does not pass 10through fully active nephrons, and as a result, the renal blood extraction rate of the best test substance PAH is 90% +. Accordingly, estimating total renal blood flow with radiopharmaceutical counterpart, ¹³¹I labelled hippuran it is possible to designate only ERPF.

This estimation of ERPF can be performed easily in patients. It typically requires measuring differential or split renal appearance of the radionuclide, 1 to 2 minutes after injection of the isotope and collecting peripheral blood 44 minutes after isotope injection to assess glomerular renal function.

3. Filtration Fraction (FF)

The filtration fraction (FF) is the fraction of plasma passing through the kidney which is filtered at the glomerulus is obtained by dividing the inulin clearance by the PAH clearance.

If we take, GFR = 125 and RPF = 594, then

Normal range = 0.16 to 0.21 in an adult.

Interpretations

The FF tends to be normal in early essential hypertension, but as the disease progresses, the decrease in RPF is greater than the decrease in the GFR. This produces an increase in FF.
In the malignant phase of hypertension, these changes are much greater, consequently the FF rises considerably.
In glomerulonephritis, the reverse situation prevails. In all stages of this disease, a progressive decrease in the FF is characteristic because of much greater decline in the glomerular filtration rate (GFR), than the renal plasma flow (RPF).
A rise in FF is also observed early in congestive cardiac failure.

C. TESTS OF TUBULAR FUNCTION

Pathophysiological aspect: Alterations in renal tubular function may be brought about by:

ischaemia with reduction in blood flow through the peritubular capillaries;
by direct action of toxic substances on the renal tubular cells; and
by biochemical defects, e.g. impairing transfer of substances across the tubular cells.

Adequate renal tubular function requires adequate renal blood flow, a significant reduction in the latter is reflected in impaired tubular function. Hence, arteriolar nephrosclerosis and other diseases diminishing blood flow, causes inability to concentrate or dilute the urine with resulting “isosthenuria” (“fixation” of sp gr at 1.010).

I. Concentration Tests

These tests are based on the ability of the kidneys to concentrate urine, and on measureing sp gr of urine.

They are simple bedside procedures, easy to carry out and extremely important. The tests are conducted either

under conditions of restricted fluid intake, or
by inhibiting diuresis by injection of ADH.

1. Fishberg Concentration Test

This test imposes less strenuous curtailment of fluid intake and may be completed in a shorter period of time. Most commonly used simple bedside concentration test.

Procedure

Patient is allowed no fluids from 8 p.m. until 10 a.m. next morning.
The evening meal is given at 7 p.m. It should be high protein meal and must have a fluid content of less than 200 ml.
Urine passed in the night is discarded
Nothing orally next morning.
Collect urine specimens next morning at 8 a.m., 9 a.m. and 10 a.m. and determine the specific gravity of each specimen.

Result and Interpretation

If tubular function is normal, the sp gr of at least one of the specimens should be greater than 1.025, after appropriate correction made for temperature, albumin, and glucose.
Impaired tubular function is shown by a sp gr of 1.020 or less and may be fixed at 1.010 in cases of severe renal damage.

Note

A false result may be obtained, if the patient has:

congestive cardiac failure because elimination of oedema fluid in night will simulate inability to concentrate;
inability to concentrate is also characteristic of diabetes insipidus.

2. Lashmet and Newburg Concentration Test

This test imposes: (i) severe fluid intake restriction over a period of 38 hours; and (ii) involves the use of a special dry diet for one day.

3. Concentration Test with Posterior Pituitary Extract

The subcutaneous injection of 10 pressor units of posterior pituitary extract (0.5 ml of vasopressin injection) in a normal person will inhibit the diuresis produced by the ingestion of 1600 ml of water in 15 minutes.

The test has the advantage of short performance time, and minimising the necessity of preparation of the patient.

Posterior pituitary extract will also inhibit the diuresis seen in congestive heart failure under active treatment as well as that of diabetes insipidus, allowing sufficient concentration to determine degree of tubular function in these conditions.

Interpretation

Under the conditions of the test, individual with normal kidney function, excrete urine with sp gr 1.020 or higher. Failure to concentrate to this degree indicates renal damage.

II. Water Dilution/Elimination Test

Principle: The ability of the kidneys to eliminate water is tested by measuring the urinary output after ingesting a large volume of water.

Note

Water excretion is not only a renal function but also depends on extrarenal factors and prerenal deviation will reduce the ability of the kidneys to excrete urine.

Procedure

The patient remains in bed throughout the test because elimination of water is maximal in the horizontal position.
On the day before the test, the patient has an evening meal but takes nothing by mouth after 8 p.m.
On the morning of the test, he empties his bladder at 8 a.m. which is discarded, and then drinks 1200 ml of water within half an hour.
The bladder is emptied at 9 a.m., 10 a.m., 11 a.m. and 12 noon and the volume and the sp gr. of the four specimens are measured.

Interpretations

If renal function is normal more than 80% (1000 ml) of water is voided in 4 hours, the larger part being excreted in the first 2 hours. The sp gr of at least one specimen should be 1.003 or less.
If renal function is impaired, less than 80% (1000 ml) of water is excreted in 4 hours, and the sp gr does not fall to 1.003 and remains fixed at 1.010 in cases of severe renal damage.

III. Tests of Tubular Excretion and Reabsorption

Principle: The reserve function of secretion of foreign non-endogenous materials by the tubular epithelium is most conveniently tested for by the use of certain dyes and measuring their rate of excretion.12

1. Phenol Sulphthalein (PSP) Excretion Test

Use of PSP (Phenol red) to measure renal function was first introduced by Rowntree and Geraghty in 1912. Later on, Smith has shown that with the amount of dye employed, 94% is excreted by tubular action and only 6% by glomerular filtration. Thus, the test measures primarily tubular activity as well as being a measure of renal blood flow.

15-minute PSP Test

It has been shown the test is reliable and sensitive if the amount of dye excreted in the first 15 minutes is taken as the criterion of renal function.

Test and Interpretation

When 1.0 ml of PSP (6 mg) is injected IV, normal kidneys will excrete 30 to 50% of the dye during the first 15 minutes. Excretion of less than 23% of the dye during this period regardless of the amount excreted in 2 hours indicates impaired renal function.

It is also used to determine the function of each kidney separately. Here, the appearance time as well as the rate of excretion of the dye is of importance. After IV injection, the normal appearance time of the dye at the tip of the catheters is 2 minutes or less and rate of excretion from each kidney is greater than 1 to 1.5% of the injected dye per ml. Increase in appearance time and decrease in excretion rate indicate impaired function.

2. Tests to Measure Tubular Secretory Mass

Principle: If diodone/or PAH concentration in the plasma is gradually raised above the level at which it is wholly excreted whilst traversing the kidney on a single occasion, the amount of diodone/PAH actually excreted per minute increases, but the removal of the presented diodone is no longer complete. Eventually a plasma concentration will be reached at which the tubules are excreting the “maximum” amount possible, they are said to be “saturated” and since they are working at their utmost capacity, further elevation of plasma diodone level produces no increase in the tubular excretion. Hence, the total excretion/minute under these conditions is the

amount excreted by glomerular filtration +
the amount excreted by the tubules.

The glomerular contribution is the glomerular volume/minute (C_In) and diodone concentration in the glomerular filtrate (P_D), since filtrate and plasma contain the same concentration.

Maximum contribution by tubules

The above represents the “tubular excretory capacity or mass” for diodone expressed in mg/minute and represented by the symbol “T_mD”.

Normally, T_mD lies in the range 36 to 72 in adults.

D. OTHER MISCELLANEOUS TESTS TO ASSESS RENAL FUNCTION

1. Test of Renal Ability to Excrete Acid

A number of workers have studied the excretion of acid by the kidneys following stimulation by giving NH₄Cl.

Procedure

Method followed here is that of Davies and Wrong (1957).

Give NH₄Cl, 0.1 gm/kg in grams or half gram gelatin coated capsules over a period of an hour, e.g., from 10 a.m. to 11 a.m.
Empty the bladder an hour later and discard the specimen.
Collect all urine specimens passed during the next 6 hours and empty the bladder at the end of that period.

13Note:

Make sure that the urine is collected in specially cleaned vessels preferably under oil. A crystal of thymol can be placed in the vessel. Measure the pH of the urine specimens and determine the NH₃ content of the combined urine specimens.

Interpretation

Normal persons pass urine during the 6-hour period with pH–5.3, and have an ammonia excretion between 30 and 90 micro-equivalents/minute.
In most forms of renal failure, the pH falls in the same way, but the ammonia excretion is low.
In renal tubular acidosis, pH remains between 5.7 and 7.0 and ammonia excretion is also low.

2. Intravenous Pyelography

When injected IV, certain radiopaque organic compounds of iodine are excreted by the kidneys in sufficient concentrations to cast a shadow of the renal calyces, renal pelvis, ureters and the bladder on an X-ray film and gives lot of informations regarding size, shape and functioning of the kidneys.

The most commonly used substances are:

Iodoxyl–available as “Pyelectan” (Glaxo), Uropac (M & B), Uroselectan B, etc.
Diodone 30%, which is recently introduced, and gives better results. Available as Perabrodil (Bayer), Pyelosil (Glaxo), etc.

Indications

IV pyelography is widely used in the investigation of diseases of urinary tract and should be a routine procedure for investigation with patients of:

renal calculi,
repeated urinary infections,
renal pain; haematuria,
prostatic enlargement,
suspected tumours; and
congenital abnormalities.

By pyelography the relationship of the renal tract to calcified abdominal shadows and masses can be demonstrated. The excretion and concentration of diodone may be used as a rough indication of renal function. If the calyces and pelvis of one kidney are outlined, while the other remains invisible, it can be assumed that the function of the invisible side is impaired.

Contraindications

IV pyelography should not be done in patients with:

acute nephritis,
congestive cardiac failure,
severely impaired liver function,
in frank uraemia
in hypersensitive patients and sensitivity to organic iodine compounds. Sensitivity test should be done before injecting the drug.

3. Radioactive Renogram

¹³¹I-labelled Hippuran is given IV and simultaneously the radioactivity from each kidney is recorded graphically in a stripchart recorder by electronic device. Hippuran-¹³¹I is actively secreted by the kidney tubules and it is not concen-trated in the liver.

A single dose 15 to 60 μci of Hippuran ¹³¹I given IV slowly.

Interpretation

With the limitations and complexities of the interpretation of the results, the investigation is of great practical clinical use. The following information is obtained.

Whether any major asymmetry in function between the two kidneys is present.
A reasonable assessment of overall renal function–Given by the ratio of bladder activity/heart activity in 10 minutes time.
The presence of obstruction to urine flow in renal pelvis or ureters.

No other means exist for obtaining so much information in a short time about the differential function of the kidneys.14

4. Radioactive Scanning

A recent development is the renal scintiscan. This has the theoretical advantage over the renogram of being able to detect segmental lesions.

In this technique, ²⁰³Hg-labelled chlormerodrin or ¹⁹⁷Hg-labelled chlormerodrin is injected intravenously and a renal scan can be obtained by a scintillation counter over the lumbar region.

Renal scanning is helpful for detection of abnormalities in size, shape and position of the kidneys.

Renal tumours and renal infarcts are shown in scintiscan which may be missed in Pyelography.

Chapter Notes

Renal Function TestsChapter 1