There are four distinct ways of measuring GFR:
1. The constant infusion technique
2. Via intravenous injections
3. Via urine samples
4. Via radioactive markers
In the constant infusion technique, a marker substance is infused continuously into a vein at a constant rate by means of a pump (which may be a portable device strapped around the waist), until the plasma concentration becomes constant. The known infusion rate is divided by this final concentration to obtain GFR in ml per minute. There is no need to collect urine. Curiously, this technique, although known for decades, has been employed in the evaluation of chronic renal failure only in the last few years. It is particularly useful in children, in whom it is more difficult to obtain timed samples of urine, but a good case can be made that it also should be used in adults. There are four disadvantages:
1. The marker substance must not be removed by any other organ, as noted earlier.
2. When kidney function is severely impaired, the steady state is reached only after a day or two of infusion, which is inconvenient to say the least.
3. Reliable portable constant infusion pumps are quite expensive.
4. The ideal marker substance to use in this technique is still being sought.
Nevertheless, wider use of this technique is likely to develop because of its accuracy and simplicity.
In a modification of the constant infusion technique that is very widely used, a GFR substance is injected intravenously, and its disappearance from the body is measured by several blood samples obtained during the ensuing hours. Many different formulas have been proposed for calculating GFR from timed blood samples. No urine samples are required, but this technique suffers from the same disadvantage as the constant infusion technique, namely, that removal of the marker by organs other than the kidney causes errors, which become amplified as the removal rate by the kidney decreases (in severe renal failure).
The urinary clearance method, the conventional method for measuring GFR, involves collecting and analyzing timed urine samples (usually three) while the marker is infused intravenously at a constant rate. Blood samples also are obtained during each collection period. The rate of excretion of the marker during each collection period is divided by the average plasma concentration during the period, to obtain its clearance, which is equal to the GFR during that period. The three estimates of GFR are then averaged.
The urinary clearance technique cannot be used if complete urine collections cannot be obtained. Many persons do not empty their bladders completely when they void, for a variety of reasons. For example, people with diabetes may have some degenerative changes in the nerves that supply the bladder. Older men often have some degree of prostate enlargement that causes residual urine to remain in the bladder after voiding. Patients whose kidney failure is the late result of congenital defects in the urinary system, many of whom develop enlarged bladders, often continue to have substantial residual urine in the bladder after voiding.
The greater the rate of urine flow, the more likely is complete emptying of the bladder. Consequently, someone undergoing this test will be encouraged to take steps to increase urine flow during the measurement of GFR. Drinking four glasses of water about an hour before the procedure starts usually will increase urine flow substantially. During the procedure, it is only necessary to continue to drink an amount of water roughly equal in volume to the volume of urine voided. In this way, the body maintains a constant water load. The water loading is begun an hour before the test because it takes an hour or so for antidiuretic hormone to disappear, after a drop in the concentration of dissolved solutes in body fluids signals the need to do so.
It is important to note that water loading can be overdone, with serious consequences. Many patients believe that the more water they drink, the better their GFR result will be. As far as I know, it is not possible to increase GFR at all by water loading; in fact, water loading may decrease GFR. However, a high urine flow does make it easier to measure.
Too much water loading can lead to a severe headache, nausea, vomiting, and even convulsions. This problem tends to be self-perpetuating, because nausea and pain are powerful stimuli for the secretion of antidiuretic hormone. Thus the patient's discomfort, brought on by too much water loading and/or by painful attempts to draw blood, may in itself make it difficult to urinate. Eventually, though, the water load is excreted and all symptoms disappear.
The major problem with the urinary clearance technique, as I noted earlier, is errors caused by incomplete urine collections. Detecting these errors is problematic in itself. Some physicians discard any results based on an arbitrary lower limit of urine flow rate, say 1 ml per minute. Another technique can be employed only if the marker substance is a gamma ray-emitting radioactive tracer. It involves determining the fraction of each voiding that remains in the bladder by measuring the radioactive emissions over the bladder before and after voiding. Using an ultrasound device to determine the amount of residual urine after voiding is another option.
It is hoped that one of these techniques will reduce the errors caused by incomplete voiding. These errors become more problematic as renal failure becomes more severe, because the maximal urine flow (during water loading) falls along with the fall in GFR. Nevertheless, we have been able to obtain consistent GFR results in patients with GFRs as low as 3 or 4 ml per minute, in whom urine flow during the test does not exceed 1 ml per minute. Many patients achieve better urine flow if they remain recumbent during the procedure.
A fourth technique involves measuring radioactivity over the kidney after injecting the patient with a gamma ray-emitting radioactive marker. So far, at least, this technique gives results that correspond very poorly to results obtained by some of the techniques already mentioned, especially in patients with chronic renal failure.
Was this article helpful?