Renal Biomarkers: Where We Are Today (Planned by ASVNU)

There is no single ideal renal biomarker. Ideally, we would be able to access a portfolio of biomarkers that reflect the different functions of all nephron segments, and that also indicate whether injury is ongoing or historical, and whether damage is permanent or reversible. Unfortunately, this diagnostic nirvana remains some way off. It is likely that different biomarkers will perform optimally in different disease states, in different species and depending on the timing of the renal insult and whether injury is ongoing. This talk will critically appraise commonly available biomarkers and challenge some assumptions about their limitations. There are many potential biomarkers currently under investigation and the intention is not to discuss all of them, but to present representative examples.

It is often stated that creatinine performs poorly as a marker of reduced renal function (and that SDMA might be more sensitive since it is less affected by muscle mass), with many studies performed to compare the performance of the two tests. However, very little attention has been given to the ability of remnant nephrons in a damaged kidney to hyper-filtrate, meaning that one of the important reasons that such surrogate markers of GFR do not increase early in kidney disease is that GFR is not actually decreased. Also, estimation of GFR (by plasma clearance, scintigraphy, or other methods) is always presumed to confer diagnostic advantages in detecting CKD earlier than using surrogate markers such as creatinine and SDMA, but actually the evidence to support this view is limited; often the error of GFR measurement is considerable, repeatability limited, and reference intervals that are used are much narrower than those permitted for standard biochemical tests.

Tubular injury/performance is usually assessed using two different types of tests; biomarkers that assess for ongoing injury (for example tubular enzymes, urinary clusterin) and evaluation of tubular function by detection of things like euglycaemic glucosuria or measurement of fractional excretion of electrolytes and other molecules. The validity of fractional excretion as an indicator of tubular (dys)function is something that is rarely challenged but in fact it is very difficult to interpret this test in clinical patients because fractional excretion of most electrolytes increases considerably as GFR decreases. It can probably only be used when making repeated measurements within the same patient, with normal renal function, when fed a standardised diet and fasted prior to the test.  

• Understand the limitation of GFR measurement as a measure of nephron number


• Recognise how laboratory harmonisation and breed-specific reference ranges could be used to improve the performance of surrogate markers of GFR such as creatinine


• Recognise why fractional excretion is a flawed test of tubular function


• Recognise that a single renal biomarker will never be adequate to represent all the different renal functions, or patterns of renal injury, but that a portfolio of tests are likely to be required for complete evaluation