Christopher P Price

St Bartholomew's and Royal London School of Medicine and Dentistry, London, UK

The kidneys play a central role in the homeostatic control of many substances, including water, and in the elaboration of urine in order to excrete water-soluble waste products (primarily nitrogenous) and toxins, thereby controlling the volume and composition of the extracellular fluid. In addition, the kidneys are responsible for some important endocrine functions, including haematopoiesis and vitamin D status. Typically, molecules under homeostatic control do not always provide sensitive and specific markers of pathological change, although they clearly represent a derangement of a homeostatic process. However, markers of functional change and structural damage can provide both sensitive and specific indications of pathological abnormality.

While a prerequisite for the utility of a biomarker is that its concentration alters as a consequence of structural or functional change, in itself this does not guarantee efficacy as a diagnostic test. Nevertheless, such information provides a valuable background to understanding the mechanisms of the underlying pathological change at a molecular, cellular or structural level. A diagnostic test can be used for either the screening, detection, diagnosis or prognosis of disease. The efficacy of a test should be judged by the ability of that test to enable a clinical decision to be made in the context of one or more of these situations. The implementation of the test then depends on its diagnostic performance and the potential clinical, operational or economic benefits that might accrue from its routine use [1]. This provides the foundation for the contribution of laboratory medicine to evidence-based clinical practice with the 'conscientious, explicit and judicious use of best evidence in the care of patients' [2].

Recognizing the fact that the availability of a diagnostic test underpins the ability to make a clinical decision and that effectiveness should determine the level of utilization, it is helpful to be aware of the pathophysiological basis for the choice of markers. In the case of biomarkers in renal disease, the pathophysiological origins of the test lie in changes in glomerular filtration rate, glomerular permeability, tubular function, tubular damage, urinary reflux, obstruction to urinary flow and deposition of collagen (fibrosis).


Figure 5.1 Schematic of the relationship between changes in glomerular filtration rate (GFR), appearance of symptoms ([ "" j) and the progression to end-stage renal disease (ESRD). This pattern is applicable to different elements of renal function.

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