Fluorescent Probe for Assessment of Renal Elimination

The majority of acutely ill patients exhibit changes in renal function due to inflammation, increased solute generation, and iatrogenic factors such as fluid resuscitation and vasopressors. The pharmacokinetics of renally eliminated medications (eg. levetiracetam, cefepime, vancomycin) are frequently affected by inflammatory processes despite normal estimations in creatinine clearance resulting in suboptimal serum drug concentrations and therapeutic failure. Despite the prevalence of fluctuations in renal function in acute illness, real-time assessment is limited to monitoring of serum biomarkers such as creatinine and cystatin C, as well as urine output, which typically lag behind important changes in function. Furthermore, use of creatinine clearance equations based on anthropomorphic data correlates poorly with actual renal function, potentially misleading clinicians as to the progression of disease and the need for dose adjustment of important medications in this vulnerable population.

Limitations of current approaches for evaluating renal function in the acutely ill Estimation of GFR or creatinine clearance can be accomplished by numerous equations, the majority of which have been validated in non-critically ill adults, usually with a relatively high percent of patients with chronic kidney disease. These equations are often not accurate in patients with acutely worsening renal function. Likewise, while these equations are helpful for categorizing renal function and assessing appropriate medication dosing in otherwise healthy, ambulatory patients. Under-prediction of creatinine clearance values leads clinicians to consistently under-dose critical medications such as beta-lactam antibiotics, vancomycin, or antiseizure medications such as levetiracetam.

Proactive measurement of creatinine clearance can provide a more accurate depiction of GFR but is fraught with complications. Iohexol serum concentrations correlate well with GFR, but requires intravenous administration of iohexol, which has a small risk of infusion reaction and hypersensitivity, and serial blood samples. Measured urine creatinine clearance is also feasible but inconvenient in most hospitalized patients. mClCr requires bladder catheterization for accurate urine volume, consistent storage on ice for the duration of collection (between 8 and 24 hours), and prompt delivery of the large volume container to the local laboratory for creatinine analysis. Each of these criteria introduce variability into the measurement and are often unnoticed or undocumented, introducing inaccuracy into the mClCr values. The lack of a real-time, accurate assessment of creatinine clearance in the acutely ill population is a gap in practice and represents a resolvable problem in the process of individualized and precision dosing of medications in this vulnerable and high-risk population.

This study represents an important innovation in advancing the understanding of fluctuations in renal function during acute illness. The current study will validate the safety of transdermal GFR monitoring to provide real-time measurement of renal function in patients with stable renal function. Further, the reliability of transdermal GFR monitoring will be compared to current standards of renal function assessment. The results of this study will advance the field by validating the use of a real-time physiologic assessment of GFR rather than using labor intensive, invasive tests that may lag behind current renal function. Numerous important gaps remain with this new technology, including use primarily in the ambulatory, stable renal function populations. Thus, this study is potentially the first step in evaluating renal function across the acute care continuum.

Inclusion criteria

• 18-65 years old
• critically ill or acutely ill hospitalized patients admitted to the intensive care unit
• Stable/normal renal function

Exclusion criteria

• Prisoners
• Pregnant women
• Laboratory evidence of unstable kidney function (KDIGO AKI stage 1-3--This includes subjects with Scr > 1.5x baseline)