The following points highlight the four main types of renal function test. The types are: 1. Glomerular Filtration Tests 2. Tests for Renal Blood Flow 3. Tests Based on Tubular Function 4. Certain Miscellaneous Test.
Types of Renal Function Test:
- Glomerular Filtration Tests
- Tests for Renal Blood Flow
- Tests Based on Tubular Function
- Certain Miscellaneous Test
Renal Function Test: Type #
1. Glomerular Filtration Tests:
i. Urea clearance test.
ii. Endogenous creatinine clearance test.
iii. Inulin clearance test.
iv. Recently, Cr51-EDTA clearance test.
The clearance of a substance is defined as the volume of blood/plasma which contains the amount of the substance which is excreted in the urine in one minute.
i. Urea Clearance Tests:
Blood urea clearance is expressed as the number of millilitre (ml) of blood/plasma which are completely cleared of urea by the kidney per minute. The plasma is not completely cleared of urea. Only about 10 per cent of the urea is removed while 750 ml of plasma passes through the kidney per minute. Hence, 10 per cent of urea is removed which is equivalent to completely clearing 75 ml of plasma per minute.
If a larger volume than normal is cleared per minute, renal function is satisfactory. But the renal function is impaired when a smaller volume is cleared. In case, the urine volume exceeds 2 ml per minute, the rate of urea elimination is at a maximum and is directly proportional to the concentration of urea in the blood.
So, the clearance which occurs when the urinary volume exceeds 2 ml per minute is termed as maximum urea clearance (Cm).
[U = Concentration of urea, V = Volume of urine in ml/minute, B = Concentration of urea in blood.]
The rate of urea elimination is reduced when the urinary volume is less than 2 ml per minute. Such clearance is termed as standard urea clearance (Cs).
Sometimes, the result of urea clearance test is expressed as the percentage of the normal maximum or of the normal standard urea clearance depending on whether urinary output is greater or lesser than 2 ml per minute.
So, normal percentage is expressed as
The urea clearance is proportional to the surface area of the body, and if the result is to be expressed as a percentage of normal, a correction must be made in the case of children and those of abnormal stature.
Procedure of the Test:
The test must be performed between breakfast and lunch since excretion is more uniform during this period.
(a) The patient at rest throughout the test is given a light breakfast and 2 to 3 glasses of water.
(b) The bladder is made emptied and the exact time of urination is noted.
(c) The urine is collected after one hour and the urea content of blood is also noted.
(d) At the end of another hour, a second specimen of urine is collected.
(e) 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 two specimens of urine is the urea content of urine.
Interpretation:
(a) Urea clearance of 70 per cent indicates the satisfactory excretion of the kidney.
(b) In mild impairment of the renal function, values show between 40 to 70 per cent; in moderate impairment, values show between 20 to 40 per cent; in severe impairment, values show below 20 per cent.
(c) In acute renal failure, Cm or Cs is lowered usually less than half the normal values.
(d) In chronic nephritis, the urea clearance falls rapidly and shows half or less of the normal values.
(e) In nephrotic nephritis, the urea clearance is usually normal until the onset of renal insufficiency sets in.
(f) Terminal uremia appears when the urea clearance falls to about 50 per cent of the normal values.
(g) In benign hypertension, a normal urea clearance is usually maintained indefinitely except in few cases.
(h) Low urea clearance value is found in normal persons with a very low protein diet.
ii. Endogenous Creatinine Clearance Test:
The metabolite creatinine is filtered at the glomerulus but neither secreted nor reabsorbed by the tubules. Hence, its clearance gives the GFR.
This method is convenient for estimation of GFR for the following reasons:
(a) It is a normal metabolite in the body.
(b) It does not require the intravenous administration of any test material.
(c) Creatinine estimation is also simple.
(d) The longer collection period of creatinine minimizes the timing error.
Procedure:
(a) The total volume of the collected 24-hour urine specimen ending at 7 AM is measured accurately.
(b) A blood sample is also collected for the determination of serum creatinine.
(c) The urinary creatinine concentration is also estimated.
... Ccr = U x V/P
where U = urine creatinine concentration in mg/dl
P = serum creatinine in mg/dl
V = volume of the urine in ml/minute
Normal values for creatinine clearance varies from 95 to 105 ml/minute.
iii. Inulin Clearance Test:
Inulin (fructosan, a homopolysaccharide) is not metabolised in the body, is excreted entirely through glomerular filtration, and is not secreted or reabsorbed by the renal tubules.
Procedure:
(a) The test is done preferably in the morning. The patient should be hospitalized overnight and kept reclining during the test.
(b) A light breakfast consisting of half a glass of milk and one sliced toast is given at 7.30 a.m.
(c) 10 grams of inulin dissolved in 100 ml. of saline at body temperature is injected intravenously at the rate of 10 ml per minute at 8 a.m.
(d) At 9 a.m. the bladder is emptied and the urine is discarded.
(e) After one and two hours, the volume of the collected urine is measured and analysed for inulin content.
(f) 8 to 10 ml of blood is withdrawn in oxalated bottle at the mid-point of each collection of urine. Plasma is separated and analysed for inulin concentration. The average of the values of two samples of blood is noted.
Calculation:
C Inu = U x V/P
where, U = mg of inulin/100 ml of urine.
V = ml of urine/minute
P = mg of inulin/dl of plasma (the average of two values)
Normal value:
Inulin clearance in an adult of 1.73 sq. m = 125 ml of plasma cleared of inulin/ minute.
Range = 110 to 150 ml.
Remark:
(a) One glass of water is given at 6.30 AM and is repeated every half an hour until the test is completed. This step should be eliminated during the administration of fluid.
(b) This test is undoubtedly superior for the determination of GFR but requires tolerable tedious chemical procedure for determination.
iv. Determination of Cr51-EDTA Clearance:
Cr51 -EDTA plasma clearance is widely used for routine assessment of glomerular filtration rate (GFR) in adults as well as in children. It is especially convenient in children where it is not easy to collect 24 hour urine sample. It is used for children younger than one year old.
4.5 µci/kg body weight of Cr51-EDTA is injected IV. Capillary blood samples are drawn at 5, 15, 60, 90 and 120 minutes after the injection and simultaneously the hematocrit (hct) is determined.
The radioactivity is calculated as measured activity in 0.2 ml. Capillary blood/l-hct. Cr51– EDTA plasma clearance is determined as the ratio between the injected amount of the ‘tracer’ (Q0) and the total area under the plasma activity curve c(t).
The plasma clearance (CI) is then calculated as
CI = Q0/(C1/b1 + C2/b2)
Renal Function Test: Type #
2. Tests for Renal Blood Flow:
Measurement of Renal Plasma Flow (RPF):
Para-amino hippuric acid (PAH) is filtered at the glomeruli and secreted by the tubules.
PAH is removed completely during a single circulation of the blood through the kidneys. Tubular capacity for excreting PAH is great.
Therefore, 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 sq. m) = 574 ml./minute.
Filtration Fraction (FF):
Filtration Fraction (FF) is the fraction of plasma passing through the kidney which is filtered at the glomerulus. This is derived by dividing the inulin clearance by the PAH clearance.
If GFR = 125 and RPF = 574, then FF = 125/574 = 0.217 (21.7%).
Normal range = 0.16 to 0.21 in an adult.
Interpretations:
(a) The filtration fraction becomes normal in early essential hypertension. FF is increased as the disease progresses.
(b) The filtration fraction (FF) is highly increased in malignant phase of hypertension.
(c) FF is also increased in congestive cardiac failure.
Renal Function Test: Type # 3. Tests Based on Tubular Function:
The sufficient renal tubular function depends on the adequate renal blood flow. Arteriolar nephrosclerosis and other diseases diminish blood flow and hence are unable to concentrate or dilute the urine resulting in “isosthenuria” (“fixation” of specific gravity at 1.010).
Concentration Tests:
The tests are conducted either (a) under conditions of restricted fluid intake, or (b) by inhibiting diuresis by injection of ADH.
(i) Fishberg concentration test:
This test is performed in a shorter period of time with less intake of fluid.
Procedure:
(a) The patient is given an evening meal at 7.0 p.m. containing high protein and a fluid containing less than 200 ml.
(b) The urine if passed in the night is discarded.
(c) The patient is kept without any fluid after 7.0 p.m. to 10.0 a.m. next morning.
(d) The urine specimens must be collected in the next morning at 8.0 a.m., 9.0 a.m. and 10.0 a.m. to determine the specific gravity of each sample.
Interpretation:
(a) In case of normal tubular function, the specific gravity of at least one of the specimens should be greater than 1.025 after suitable correction for temperature, albumin and glucose.
(b) At least one of the urine specimens shows a specific gravity of 1.020 or less in case of impaired tubular function and the specific gravity becomes fixed at 1.010 in severe renal damage.
(c) A false result is also expected in case of congestive cardiac failure and diabetes insipidus owing to the inability of the elimination to be concentrated.
(ii) Water dilution/Elimination test:
The ability of the kidneys to eliminate water is tested by ingesting a large volume of water after measuring the urinary output.
Procedure:
(a) The patient should take an evening meal and should not take anything after 8.0 p.m.
(b) On the next morning, he should empty his bladder at 8.0 a.m. which is discarded and then within half an hour he must be allowed to drink 1200 ml of water.
(c) His bladder is emptied at 9.0 a.m., 10.0 a.m., 11.0 a.m., and 12.0 noon. The volume and the specific gravity of these four specimens should be measured.
(d) The patient must be in bed during the test, since elimination of water is maximum in the horizontal position.
Interpretation:
(a) In case of normal renal function, the excretion of water is more than 80 per cent in four hours and the specific gravity of at least one specimen must be 1.003 or less.
(b) But in case of impaired renal function, less than 80 per cent of water is excreted in four hours and the specific gravity of at least one specimen does not fall to 1.003. The specific gravity of one specimen rather becomes fixed at 1.010 in severe renal damage.
(iii) Concentration test with posterior pituitary extract:
(a) The subcutaneous injection of 0.5 ml of vasopressin to a normal person inhibits the diuresis.
(b) This test is performed within a short period of time and does not require any preparation of the patient.
(c) In case of congestive heart failure and diabetes insipidus, the posterior pituitary extract inhibits the diuresis causing sufficient concentration to determine degree of tubular function.
(d) In case of person with normal kidney function, the specific gravity of excreted urine becomes 1.020 or more and failure to this degree indicates renal damage.
(iv) Phenol sulfthalein (PSP) excretion test:
This test is reliable and sensitive if the amount of dye in the first 15 minutes is taken as the criterion of renal function.
Procedure:
1.0 ml of PSP (6 mg) is injected intravenously to a patient. Observation should be done after 15 minutes.
Interpretation:
(a) Normal kidneys excrete 30 to 50 per cent of the dye during the first 15 minutes.
(b) Impaired renal function is confirmed if less than 23 per cent of the dye is excreted during this period.
Renal Function Test: Type #
4. Certain Miscellaneous Test:
(i) Test of Renal Ability to Excrete Acid:
Procedure:
(a) Half a gram of gelatin coated capsules should be given over a period of an hour.
(b) The bladder should be emptied an hour later and the specimen must be discarded.
(c) All passed urine specimens must be collected during the next 6 hours and the bladder should be emptied at the end of that period.
(d) The urine must be collected in cleaned vessels containing a crystal of thymol.
(e) The pH of the urine specimens should be measured and the ammonia content of the combined urine specimens must also be determined.
Interpretation:
(a) In case of normal persons, the pH is 5.3 of the passed urine during the 6-hour period and the value of ammonia excretion is between 30 and 90 micro equivalents/minute.
(b) The pH of the passed urine falls but ammonia excretion is low in case of renal failure.
(c) The pH of the urine is between 5.7 and 7.0 and ammonia excretion is also low in renal tubular acidosis.
(ii) Intravenous Pyelography:
(a) After the injection of radio-opaque organic compounds intravenously, certain compounds of iodine are excreted by the kidneys in adequate concentrations to form a shadow of the renal calyces, renal pelvis, ureters, and the baldder on an X-ray film and provides sufficient information regarding size, shape, and functioning of the kidneys.
(b) The most recently used substance is diodone (30 per cent) which gives better results and available as pyelosil (Glaxo). The excretion of diodone is used as a rough indication of renal function.
(c) Intravenous pyelography is used in the investigation of urinary tract diseases and it becomes a routine procedure for the investigation of patients suffering from renal calculi, repeated urinary infections, renal pain, hematuria, prostatic enlargement and suspected tumors, etc.
(d) This pyelography should not be done in case of patients suffering from acute nephritis, severely impaired liver function, congestive cardiac failure, hypersensitivity, etc.
(iii) Radio-active Renogram:
(a) The radioactivity of each kidney is recorded graphically after the administration of I131-labelled hippuran intravenously. This hippuran-I131 is actively secreted by the kidney tubules and is not concentrated in the liver.
(b) 15 to 60 µci of hippuran-I131 is given slowly intravenously by a single dose.
(c) This investigation gives the information regarding the major asymmetry in function between the two kidneys, the assessment of overall renal function, and the presence of obstruction to urine flow in renal pelvis or ureters.
(a) This is the recent developed technique and in this technique, Hg197labelled chlormerodrin is injected intravenously. A renal scan can be obtained by a scintillation counter over the lumbar regions.
(b) This technique is useful for the detection of abnormalities in size, shape, and position of the kidneys.
(c) This technique also shows renal tumors and renal infarcts which are not detected in pyelography.