Measuring glomerular filtration rate in the intensive care unit: no substitutesplease
Critical Care volume 17, Article number: 181 (2013)
Acute kidney injury (AKI), due to its increasing incidence, associated morbidityand mortality, and potential for development of chronic kidney disease withacceleration to end-stage renal disease, has become of major interest tonephrologists and critical care physicians. The development of biomarkers todiagnose AKI, quantify risk and predict prognosis is receiving considerableattention. Yet techniques to accurately assess functional changes withinpatients still rely on the use of an insensitive marker (creatinine),creatinine-based estimating equations and unreliable urinary tests. Therefore,it is critical that functional tests be developed and used in combination withbiomarkers, thus allowing improved care in AKI and chronic kidney diseasepatient populations.
Bragadottir and colleagues found utilization of glomerular filtration rate (GFR)estimating equations of limited value, no value or perhaps even negative value inintensive care unit (ICU) acute kidney injury (AKI) patients . They confirmed the limited, inaccurate and highly variable data obtainedfrom urinary creatinine collections to quantify the GFR. They acknowledge this hadbeen shown before and point to inaccurate urine collections and variable release ofcreatinine from muscle as problems [2–4]. Unfortunately, the available tests to quantify the GFR utilize asingle-compartment model that requires several hours for equilibration between theplasma volume and extracellular fluid space. In addition, they require laboratorydeterminations that are complex, sensitive to user error, time consuming andexpensive.
The use of serum creatinine, and the accompanying equations to estimate the GFR inpatients with stable kidney function, has been beneficial in longitudinal populationstudies where trends are followed and the known wide variation between calculatedand determined GFRs is acceptable. The necessity of a plasma equilibrium state forcreatinine, based on the stable release of creatinine from muscle and stable removalby the kidney via the GFR, is well known in these situations. In states of AKI,however, these necessary parameters do not hold and thus it is predictablyimpossible to use serum creatinine or equations based on serum creatinine.
Further complicating the use of these parameters in the acute situation is theavailability of renal reserve. The renal reserve represents the ability of thenormal kidney to increase the GFR following specific challenges such as ahigh-protein meal, early diabetes, unilateral nephrectomy or progressive loss ofkidney function . Renal reserve can be >50% of baseline unstimulated kidney function,thus increasing the GFR from 100 ml/minute/1.73 m2 to >150ml/minute/1.73 m2. Renal reserve may therefore be one reason why the GFRcan fall to 50% of normal values prior to detection based on a rise in serumcreatinine. This observation has made the use of serum creatinine insensitive as amarker of development of chronic kidney disease and is in part why the estimatingequations for the GFR are not useful above a GFR of 50 to 60 ml/minute/1.73m2. In theory, therefore, a patient could have lost up to 67% oftheir baseline total GFR, going from a potential GFR of 150 ml/minute/1.73m2 to one of 50 ml/minute/1.73 m2 prior to a change inserum creatinine (Figure 1). We know very little aboutrenal reserve in AKI.
An additional problem with serum creatinine as a marker of kidney function in casesof AKI is the slow rate of rise to an equilibrium state. In a noncatabolic 70 kgpatient, if you were to remove both kidneys the serum creatinine would rise by only1 mg/dl/day. Thus, 1 day post bilateral nephrectomy the patient’s serumcreatinine would be 2 mg/dl, on day 2 it would be 3 mg/dl, and so on, even thoughthe patient has zero GFR. Patients with severe AKI therefore sit in the ICU waitingfor blood chemistries, or their volume status, to rise to renal replacement levels,all the while being in a state we believe requires renal replacement therapy forappropriate support. Add to this the other factors known to confound serumcreatinine as a marker of the GFR and is there any wonder why its use in the ICU,where accurate quantitative data are a must, is resulting in less than maximal careof the patient [6–10].
On a brighter note, commercial attempts have been initiated to develop a rapid,sensitive, reproducible, affordable and user-friendly GFR technique [9, 11]. Clearance of a freely filterable water-soluble molecule is being usedwith either noninvasive or minimally invasive approaches. Both one-compartment andtwo-compartment models are being developed, with two-compartment approaches offeringa more rapid result because equilibration with the extracellular fluid is not needed . FAST BioMedical (Indianapolis, IN, USA) has recently completed a phaseI, single-blind, dose escalation study in normal patients with satisfactory results(unpublished observation; see Competing interests statement).
Perhaps a more intriguing question for the clinician to now consider is, whenavailable, how will a GFR test be used to advance care in the hospitalized patient?To commercialize such a product there must be defined clinical pathways resulting inmeaningful, cost-effective and patient-beneficial outcomes that can be standardizedfor general use. In AKI, functional confirmation and quantification of the severityof injury would allow the physician to determine the immediate need for renalreplacement therapy. Additionally, the response to hydration or pressor therapycould be quantified with a second test post-therapy. Weaning from continuousveno-venous hemofiltration therapy or movement of the patient to the ward, based onthe return of kidney function that is now quantifiable, may minimize valuable daysin the ICU. Knowing the actual GFR for drug dosing of renally cleared drugs ornephrotoxins may provide more reliable serum levels. Accurate GFRs would alsoaccurately identify patients with low GFRs requiring preventative therapies prior touse of agents such as radiocontrast or gadolinium.
The field of nephrology has lagged in the development of diagnostic technology.However, it now seems time to turn attention to the care of the AKI and chronickidney disease patient in an effort to minimize, or at least forestall, thedevelopment of end-stage renal disease and requirement for chronic renal replacementtherapy. Individualization of patient care will come through innovation and itscareful application. The cost of such development and utilization can be easilyrationalized based on the patient and societal costs of end-stage renal care ofchronic dialysis patients.
Acute kidney injury
Glomerular filtration rate
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BAM is a co-founder, part owner, and medical director of FAST Biomedical(Indianapolis, IN, USA).
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Molitoris, B.A. Measuring glomerular filtration rate in the intensive care unit: no substitutesplease. Crit Care 17, 181 (2013). https://doi.org/10.1186/cc12876