acute kidney injury ( aki ) remains a vexing clinical problem resulting in unacceptably high patient mortality , development of chronic kidney disease , and enhanced progression to end - stage kidney disease . although clinical risk factors for developing aki have been identified , there is no reasonable surveillance technique ( ' biomarker ' ) to either definitively and rapidly diagnose the injury or determine the extent of its severity . since patient outcomes correlate with the extent of injury and effective therapy requires early intervention , the ability to rapidly diagnose and stratify patients by their level of kidney injury is of paramount importance for therapeutic progress . therefore , a search for a biomarker of kidney injury has intensified and is now considered by many experts to be the highest priority in the field of aki . it is likely that a combination of structural and functional markers of aki will provide the highest clinical utility . glomerular filtration rate ( gfr ) , which measures the amount of plasma filtered through glomeruli within a given period of time , is clinically the most widely used indicator of kidney function . yet reduction in the gfr , secondary to kidney injury , is the hallmark of aki and results in increased levels of blood urea nitrogen ( bun ) and serum creatinine . unfortunately , the rates of increase in bun and serum creatinine do not parallel the fall in gfr in a time frame that is clinically useful . in addition , since both creatinine production from muscle and gfr determine the serum creatinine level , using serum creatinine as an indicator of gfr is highly patient - specific and often problematic or even misleading . achieving the ability to rapidly and accurately measure gfr in an early stage of aki would be beneficial for many reasons . it would rapidly identify and determine the extent of injury , allowing early pharmacologic or dialytic treatment ( or both ) , enrollment and stratification for clinical studies , and prognostic information . it could also be used to determine the effect of a clinical maneuver on gfr , such as volume resuscitation and the use of pressors to support blood pressure , and enable appropriate drug dosing for agents cleared by the kidney or nephrotoxins . on this well - known background , pickering and colleagues   set out to determine the clinical utility of a 4-hour creatinine clearance ( crcl ) , compared with plasma creatinine , for diagnosing aki . the authors found that crcl increased the likelihood of diagnosing aki ; a decreasing crcl correlated with increased kidney injury severity , death , or dialysis ; and the crcl was most helpful when patients began with a serum creatinine in the normal range . although the receiver operating characteristics were not impressive , the study was a small pilot study . this is not the first time a shortened crcl has been used to estimate gfr in clinical settings . herget - rosenthal and colleagues   used a 2-hour crcl in stable patients and found an acceptable and repeatable correlation with the 24-hour crcl . however , the accuracy and utility of a shortened collection in unstable patients were questioned by two studies conducted in patients with aki . this limitation may relate to reduced production of creatinine in sepsis , increased production of creatinine with trauma , increased metabolism including the use of glucocorticoids , or the changing of gfrs during the collection periods . pickering and colleagues did not attempt to validate their 4-hour crcl rates with 6-hour iohexol or iothalamate infustion studies , currently the gold standard for clinical studies . this validation could have been done nearly simultaneously with the 4-hour crcl urine collection . until such studies are conducted , confidence for using a crcl may be limited . a clinically useful technique to measure gfr in aki has been a long - sought - after goal . the cumbersome , time - consuming , and expensive techniques currently available have not met this important clinical need . the development and use of estimating formulas based on serum creatinine or cystatin c have been disappointing for several well - explained reasons . therefore , the development of a rapid , accurate , safe , easy , and in - expensive technique has high clinical importance both in and out of the hospital . an approach being developed commercially , used primarily in preclinical studies to date , is the use of bedside techniques to measure gfr . the use of inexpensive , nontoxic , easily sized fluorescent molecules has emerged as a likely candidate , and several groups are now working with this approach in preclinical models . it is likely that several of these approaches will enter clinical phase studies , and improvements in design and clinical utility are continually being developed . test rapidity , convenience , cost , safety , accuracy , and repeatability are all critical characteristics . hopefully , one or more of these approaches will emerge and alleviate the need for multiple - hour urine collection and analysis . aki : acute kidney injury ; bun : blood urea nitrogen ; crcl : creatinine clearance ; gfr : glomerular filtration rate . bam is a co - founder and part owner and the medical director of fast biomedical ( indianapolis , in , usa ) .
acute kidney injury has become a major focus for nephrologists and critical care physicians . 
 the development of structural biomarkers is proceeding , but the results to date have been disappointing . the use of a shortened creatinine clearance as a functional acute kidney injury biomarker is not new but has not been compared with that of other diagnostic approaches 
 . a rapid , repeatable , and accurate measured glomerular filtration rate would be the gold standard for a functional biomarker and is not far off .