by measuring the concentration of sodium ions, [Na+], within it. The cells within the glomeruli, the juxtaglomerular cells then act 011 signals from the macula densa to constrict/dilate the afferent arterioles, thus altering GFR.
In adition to this local effect on renal blood pressure, the tubuloglomerular feed
back also has an additional systemic effect 011 blood pressure since its causes the juxtaglomerular cells to secrete renin, an enzyme involved in the production of
angiotensin II, a potent systemic vasoconstrictor which increases GFR.
Mean arterial blood pressure (mm Hg)
Figure 1.3: Autoregulation of GFR. From Imholtz (2008)
Having presented an introduction to the kidneys and the process of renal filtration, the next section provides an overview of the techniques used currently for renal function assessment (using non-imaging techniques).
1.3 Non Image-based Renal Function Assessment
There are numerous techniques developed to evaluate renal function. Some of the most widely used non-invasive techniques are based either on the concept of plasma clearance or on the measurement of plasma concentration alone for the estimation of the most important parameters for the diagnosis of renal disease: namely, renal blood flow and glomerular filtration rate.
1.3.1 Measuring Renal Plasma Flow and Renal Blood Flow
simplifying the above equation. Such a substance is para-aminohippurate (PAH). PAH is an organic acid that is both filtered at the glomerulus and extensively secreted by the proximal tubule, resulting in an extraction fraction (i.e first-pass clearance) that approaches 90%. Therefore, an approximate RPF (underestimated by ~ 1 0 % ) can be found using PAH, known as Effective Renal Plasma Flow (ERPF). Thus:where
P[pah] and P[pai-i]
indicate PAH concentration in urine and systemic/renal arterial plasma respectively. Since PAH is not metabolised and no organ, except the kidney, extracts PAH from the blood, the PAH concentration in the renal artery is equal to the concentration in any non-renal peripheral vein. This can be easily sampled.
that is composed of cells. Thus, knowing RPF and Hct, Renal Blood Flow (RBF) can be found so that:
Concentration is most commonly expressed as Molarity (M) = No. of moles/litres of solvent.
Another commonly used measure of concentration is Molality (m) — No. of moles/kg. of solvent.
_ U[x]Fu
1.3. Non Image-based Renal Function Assessment
9R BF = RPF + (RBF x Hct)
rearranging:
R PF
R B F = ( I ^ )
E R P F measurements using PAH need a constant intravenous infusion to achieve a constant FjpAH] and timed urine samples to measure urine flow. Urine sampling is particularly prone to error, and the whole procedure is time consuming and expensive.
Thus, R BF estimation is not widely used in the clinical diagnosis of renal disease.
However, accurate measurement of RBF is an active area of research, as this is the most important parameter for the assessment of pathology in the renal vasculature.
1.3.2 Measurement of Glomerular Filtration Rate
As already discussed, G FR estimation is the most important functional test in renal medicine. GFR, the total plasma volume filtered by the glomeruli per unit time, can be measured by the use of some particular substance X that is freely filtered but is not re-absorbed, secreted, stored or metabolised, so that the amount excreted equals the amount filtered indiscriminately at the glomerulus. Such a substance is inulin, a fructose polymer that is not metabolised and is cleared only by glomerular filtration.
Thus, G F R can be calculated using again the concept of clearance such that:
G FR = M i ( L 4 )
Uinu)
where C/pnuj and P[inu] indicate inulin concentration in urine and plasma respectively.
Just as with RBF in the previous section, G FR measurement using the above formula for inulin requires a constant intravenous infusion and has urine collection requirements that are not usually met by patients with compromised renal function. Thus, even though inulin clearance is considered to be the gold standard in G F R measurement, in practice it is only used as a research tool.
Clinically, creatinine is used instead of inulin to determine renal clearance. Creatinine, a product of muscle metabolism, is freely filtered at the glomerulus and is not re
absorbed. However, it is secreted by the tubules and, therefore, the clearance formula overestimates GFR. However, G FR measurement using creatinine clearance does not require intravenous infusion and the clearance period can be extended (usually 24 hours) so that adequate amounts of urine can be obtained. This makes it preferable to inulin clearance for routine medical practice.
Measurement of Glomerular Filtration Rate using Plasma Concentration
To avoid the problems associated with urine collection, G FR can also be estimated from the measurement of the plasma creatinine alone since G FR is approximately inversely proportional to plasma creatinine concentration, P[cr]- The Cockroft-Gault formula (Cockcroft and Gault, 1976) takes into account patient weight and gender to produce an estimate of creatinine clearance (C cr):
c (140 - age) x weight x Cg
P M
where C (J is 1 for men and 0.85 for women.
There are several variations and modifications on the Cockroft-Gault formula, including other factors, such as the Modification of Diet in Renal Disease (M DRD) formula (Levey et al., 1999) which also accounts for racial origin. Such methods, based on collecting a series of plasma samples and using plasma creatinine concentration formulae, are the basis for G FR measurement in clinical practice (Baker, 1998).
In addition to the plasma concentration methods for estimating renal function using creatinine described above, there are others based on the use of radiopharmaceuticals (radionuclide3-labelled substances). Radionuclides were first used to assess renal func
tion by Oeser and Billion (1952), who measured the remaining traces in urine of a