image
Chapter 26

FLCs are present in similar concentrations in the vascular and extravascular compartments [529]. As a consequence, the vascular compartment may contain only 15-20% of the total amount of FLCs in the body. The serum concentrations of κ and λ FLCs are dependent upon the balance between production and clearance (Chapter 3). Although κ FLCs are normally produced at a rate approximately twice that of λ FLCs, the renal clearance of monomeric κ FLCs is faster than dimeric λ FLCs. This accounts for the observed differences in their serum half-lives (κ sFLCs: approximately 2 hours; λ sFLCs: 4 - 6 hours) and their serum concentrations (Chapter 3 and Section 6.1) [94][95]. The molecular weight cut-off for glomerular filtration of circulating macromolecules is around 60 kDa. Therefore, whilst sFLCs are rapidly cleared from the blood by the kidneys, larger serum proteins such as albumin (66 kDa) and transferrin (81 kDa) are only filtered to a limited extent [99] and their serum concentrations are not dependent upon kidney function.

After filtration by the glomeruli, FLCs and other proteins enter the proximal tubules and bind to brush border membranes via low-affinity, high-capacity receptors called cubulin and megalin [99]. Binding results in internalisation of the bound proteins followed by proteolysis within the tubular epithelial cells. Subsequently, the constituent amino acids are returned to the circulation across the basolateral membrane [99]. Reabsorption of FLCs by the proximal tubule is highly efficient and a normal 24-hour urine collection will only contain around 10 mg of polyclonal FLCs [81].

Whilst the concentration of serum creatinine is a useful guide to kidney function, the glomerular filtration rate (GFR) is a more accurate measure. Estimated GFR (eGFR) values can be derived from various different calculations. Currently, the most widely used calculation is the one proposed by the Modification of Diet in Renal Disease (MDRD) study group, which incorporates serum creatinine along with age, sex, and ethnicity in the equation to produce an eGFR [532]. More recent calculations may be more accurate than the MDRD equation for kidney function measurement; in particular the CKD-EPI equation may replace MDRD in routine clinical practice in the near future [533].