Glomerular filtration rate is the accepted best indicator of kidney function. Any
pathology of the kidneys is reflected in a decreased GFR and this in turn has serious
physiological consequences including anaemia and severe cardiovascular disease.
Kidney disease is a progressive one, proceeding through subacute or intrinsic renal
disease such as glomerular nephritis into chronic kidney disease (CKD). Complete
kidney failure leads to the need for kidney dialysis and kidney transplantation. There
is evidence that the incidence of CKD is increasing in developed countries and is
associated with increasing risk of diabetes and an increasingly elderly population.
There is thus a great clinical demand for accurate measurements of GFR in order to
detect the onset of kidney disease, to assess its severity and to monitor its subsequent
progression.Measurement of glomerular filtration rate
The measurement of GFR is based on the concept ofrenal clearancewhichisdefinedasthe
volume of serum cleared of a given substanceby glomerular filtration in unit time. It
therefore has units of cm^3 min^1. In principle any endogenous or exogenous substance
that is subject to glomerular filtration and is not reabsorbed could form the basis of the
measurement. The polysaccharide inulin meets these criteria and is subject to few variables
or interferences but because it is not naturally occurring in the body is inconvenient for
routine clinical use but is commonly used as a standard for alternative methods. In practice
serum creatinine is the most commonly used marker. It is the end product of creatine
metabolism in skeletal muscle and meets the excretion criteria so that its serum concen-
tration is inversely related to GFR. However, it is subject to a number of non-renal
variables including:- Muscle mass: Serum values are influenced by extremes of muscle mass as in athletes
and in individuals with muscle-wasting disease or malnourished patients. - Gender: Serum creatinine is higher in males than females for a given GFR.
- Age: Children under 18 years have a reduced serum creatinine and the elderly have an
increased value. - Ethnicity: African–Caribbeans have a higher serum creatinine for a given GFR than
have Caucasians. - Drugs: Some commonly used drugs such as cimetidine, trimethoprim and
cephalosporins interfere with creatinine excretion and hence give elevated GFR values. - Diet:Recent intake of red meats and oily fish can raise serum creatinine levels.
Routine laboratory estimations of GFR (referred to aseGFR) are based on the measure-
ment of serum creatinine concentration and the calculation ofeGFR from it using an
equation that makes corrections for four of the above variables. Serum creatinine is
routinely measured by one of two ways: - Spectrophotometric method based on the Jaffe reaction: This involves the use
of alkaline picric acid reagent which produces a red-coloured product that is measured
at 510 nm. A limitation is that the reagent also reacts with some non-creatinine
chromogens such as ketones, ascorbic acid and cephalosporins and as a result gives
high values.
647 16.3 Examples of biochemical aids to clinical diagnosis