Biomarkers in assessment of acute kidney injury

This has been asked about in Question 2 from the first paper of 2010. I answered it with a table. That table is reproduced below without any substantial alteration.

A Comparison of Biomarkers in the Assessment of Acute Kidney Injury
Marker Physiology Advantages Disadvantages
  • A breakdown product of creatine phosphate in muscle
  • Excreted unchanged by the kidneys
  • Simple to measure
  • Cheap
  • Widely available
  • Indicator of GFR if its production remains constant
  • Indicator of a change in renal function when viewed as a trend
  • Dependent on muscle metabolism rate remaining normal
  • As renal function worsens, tubular secretion accounts for more of the total creatinine secretion, and its relationship to glomerular filtration rate is thus diluted
  • Relies of accuracy of collection (i.e. did you collect all the urine over 24hrs?)
  • In AKI, frequently overestimates GFR by as much as twofold
  • Increase in creatinine and change in creatinine clearance is delayed for some period after the onset of kidney injury
Creatinine clearance
  • Correlates with GFR
  • Requires 24hr urine collection
  • Alterantively, can be calculated froms erum creatinine using the Cockcroft-Gault formula
  • Under ideal circumstances, correlates with GFR
  • Cheap
  • Easy to collect
  • Widely available
  • Product of ammonia metabolism and thus a product of amino acid deamination.
  • Filtered and excreted passively by the kidney
  • Simple to measure
  • Cheap
  • Related to pathology (high urea has consequences, eg. encephalopathy and platelet dysfunction)
  • Less specific than creatinine
  • Elevated in a number of conditions
  • Levels related not only to renal function but also to rates of protein metabolism
  • Influenced by dietary protein intake
Urine output
  • The fraction of the filtered fluid which is not reabsorbed
  • Simple to measure
  • Cheap
  • Related to pathology (low urine output can result in fluid overload)
  • Non-specific, except severely decreased or absent
  • Severe AKI can exist wih normal or increased urine output
Urinary NGAL
  • Less effective in a general ICU population
  • Expensive
  • Experimental
  • Requires urine (there may not be any)
Cystatin C
  • A 13-kDa, nonglycosylated basic protein, produced at a constant rate by all nucleated cells.
  • Freely filtered by glomeruli and catabolized in tubules
  • Poor predictor of the need for RRT in a heterogeneous ICU population
  • Expensive
  • Experimental
Urinary IL-18
  • Less helpful in detecting glomerular injury
  • Expensive
  • Experimental
Urinary KIM-1
  • Less helpful in detecting glomerular injury
  • Expensive
  • Experimental
  • Only sensitive and specific for one aetiology of AKI

If one were a time-poor exam candidate in need of a single resource for novel biomarkers, this systematic review in Nature would be my recommendation.


Parikh, Chirag R., et al. "Urinary interleukin-18 is a marker of human acute tubular necrosis." American Journal of Kidney Diseases 43.3 (2004): 405-414.

Devarajan, Peasad. "Neutrophil gelatinase-associated lipocalin (NGAL): a new marker of kidney disease." Scandinavian Journal of Clinical & Laboratory Investigation 68.S241 (2008): 89-94.

Bennett, Michael, et al. "Urine NGAL predicts severity of acute kidney injury after cardiac surgery: a prospective study." CLINICAL JOURNAL-AMERICAN SOCIETY OF NEPHROLOGY 3.3 (2008): 665.

Herget-Rosenthal, Stefan, et al. "Early detection of acute renal failure by serum cystatin C." Kidney international 66.3 (2004): 1115-1122.

Royakkers, Annick ANM, et al. "Serum and urine cystatin C are poor biomarkers for acute kidney injury and renal replacement therapy." Intensive care medicine 37.3 (2011): 493-501.

Coca, S. G., et al. "Biomarkers for the diagnosis and risk stratification of acute kidney injury: a systematic review." Kidney international 73.9 (2007): 1008-1016.

Shemesh, Ovadia, et al. "Limitations of creatinine as a filtration marker in glomerulopathic patients." Kidney Int 28.5 (1985): 830-838.

Waikar, Sushrut S., and Joseph V. Bonventre. "Creatinine kinetics and the definition of acute kidney injury." Journal of the American Society of Nephrology20.3 (2009): 672-679.

Bellomo, Rinaldo, et al. "Acute renal failure–definition, outcome measures, animal models, fluid therapy and information technology needs: the Second International Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group." Critical care 8.4 (2004): R204.

Cockcroft, Donald W., and M. Henry Gault. "Prediction of creatinine clearance from serum creatinine." Nephron 16.1 (1976): 31-41.

Han, Won K., et al. "Kidney Injury Molecule-1 (KIM-1): a novel biomarker for human renal proximal tubule injury." Kidney international 62.1 (2002): 237-244.