12–15 In addition to aiding in the early diagnosis and prediction, they should be highly specific for AKI, and enable the identification
of AKI subtypes and aetiologies. AKI is traditionally diagnosed when the kidney’s major function BMS-777607 datasheet (glomerular filtration) is affected, and indirectly measured by change in serum creatinine. However, pre-renal factors such as volume depletion, decreased effective circulating volume or alterations in the calibre of the glomerular afferent arterioles all cause elevations in serum creatinine. Post-renal factors such as urinary tract obstruction similarly result in elevations in serum creatinine. Finally, a multitude of intrinsic renal diseases may result in abrupt rise in serum creatinine, particularly in hospitalized patients. Other tests to distinguish these various forms of AKI such as microscopic urine examination for casts and determination of fractional excretion Everolimus of sodium have
been imprecise and have not enabled efficient clinical trial design. Availability of accurate biomarkers that can distinguish pre-renal and post-renal conditions from true intrinsic AKI would represent a significant advance. Biomarkers may serve several other purposes in AKI.12–15 Thus, biomarkers are also needed for: (i) identifying the primary location of injury (proximal tubule, distal tubule, interstitium or vasculature); (ii) pinpointing the duration of kidney failure
(AKI, chronic kidney disease (CKD) or ‘acute-on-chronic’ kidney injury); (iii) identifying AKI aetiologies (ischaemia, toxins, sepsis or a combination); (iv) risk stratification and prognostication (duration and severity of AKI, need for dialysis, length of hospital stay, mortality); and (v) monitoring the response to AKI interventions. Furthermore, AKI biomarkers may play a critical role in expediting the drug development process. The Critical Path Initiative first issued by the Food and Drug Administration in 2004 stated that ‘Additional biomarkers (quantitative measures of biologic effects that provide informative links between mechanism of Reverse transcriptase action and clinical effectiveness) and additional surrogate markers (quantitative measures that can predict effectiveness) are needed to guide product development’. Collectively, it is envisioned that biomarkers will play an indispensable role in personalizing nephrologic care, by providing a more precise determination of disease predisposition, diagnosis and prognosis, earlier preventive and therapeutic interventions, a more efficient drug development process, and a safer and more fiscally responsive approach to medicine.