Glomerular filtration rate

In health the GFR remains remarkably constant owing to intrarenal regulatory mechanisms.

In disease, with a reduction in intrarenal blood flow, damage to or loss of glomeruli, or obstruction to the free flow of ultrafiltrate along the tubule, the GFR will fall and the ability to eliminate waste material and to regulate the volume and composition of body fluid will decline. This will be manifest as a rise in the blood level of urea or the plasma level of creatinine and in a reduction in measured GFR.

Measurement of the glomerular filtration rate

Measurement of the GFR is necessary to define the exact level of renal function. It is essential when the serum (plasma) urea or creatinine is within the normal range.

Inulin clearance - the gold standard of physiologists - is not practical or necessary in clinical practice. The most widely used measurement is the creatinine clearance.

The use of creatinine clearance is dependent on the fact that daily production of creatinine (principally from muscle cells) is remarkably constant and little affected by protein intake. Serum creatinine and urinary output thus vary very little throughout the day. This permits the use of 24-hour urine collections, which reduce collection errors, and the measurement of a single serum creatinine value during the 24 hours.

Creatinine excretion is, however, by both glomerular filtration and tubular secretion, although at normal serum levels the latter is relatively small. As most laboratory methods for measurement of serum creatinine give slight overestimates, the calculation of clearance fortuitously gives a value close to that of inulin.

With progressive renal failure, creatinine clearance may overestimate GFR but, in clinical practice, this is seldom important. Certain drugs - for example cimetidine, trimethoprim, spironolactone and amiloride - reduce tubular secretion of creatinine, leading to a rise in serum creatinine and a fall in measured clearance.

Given these observations, creatinine clearance, nevertheless, is a reasonably accurate measure of GFR in those situations in which it is most required - normal or near normal renal function.

Where urine collections are difficult (e.g. with ileal conduits) or deemed inaccurate, the GFR may be measured by the single injection of compounds such as [ 51 Cr]EDTA (ethylenediaminetetraacetic acid), [ 99m Tc]DTPA (diethylenetriaminepentaacetic acid) or [ 125 I]iothalamate, their excretion being primarily by glomerular filtration. Following intravenous injection of the compound, three blood samples are obtained at 2, 3 and 4 hours (or rather longer intervals if the patient is oedematous or if renal failure is suspected). The GFR may then be calculated from the slope of the exponential fall in blood level of the compound.

Urea clearance is not an accurate measure of GFR, particularly when urine flow rate is low, and should not be used as a measure of GFR.

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