Creatinine, an oldie but a goodie? Creatinine is a breakdown product of creatine kinase in skeletal muscle. First found in blood in 1896, it was noticed that levels go way up with chronic kidney disease in the 1910's. We've been fixated on it every since as the biomarker for kidney function. It's been routinely measured on hospital inpatients for at least 60 years. It's worth reviewing it strengths and weaknesses.
In the strength column, we can place that we have lots of experience with it. It's widely available, cheap to measure and tracks chronic disease quite nicely. Downsides? First, I've never liked saying it. It's a funny word. Second, the production of creatinine is highly variable, dependent on multiple factors including age, sex, race, muscle mass, nutritional state and others. Second, up to 40% of urinary creatinine is secreted by the tubules not filtered. In other words, it will never directly correlate with GFR as well as something that is not secreted at all, such as cysatinC (CysC). This leads to delays in the diagnosis of acute drops in GFR. Which brings us to the third major problem: It's slow. When the kidney filtering slows or stops, it takes days the serum creatinine to rise because basal production rates are so slow. Currently, we have to wait 2 days to learn the kidneys have been injured, beyond the time when interventions are thought to possibly improve outcomes. Its like trying to diagnosis an acute MI without troponins and just waiting to see how it will all settle out.
These limitations have lead to the intense development of serum and urinary biomarkers that better reflect GFR, give real time information about kidney injury and will, in all likelihood, make our old friend creatinine obsolete for ICU use with in 10 years . We've got several great candidates which work quicker, correlate better with disease severity and give more prognostic information coming down the pipeline, some of which are already being used in POC testing around the world (NGAL, KIM-1, L-FAB).
Rabinowitch IM. The prognostic value of the study of the blood creatinine in nephritis: based upon the study of fourteen cases with complete postmortem examination. Can Med Assoc J 1921; 11:320–322.
Moore, E, et al. Novel biomarkers of acute kidney injury: ready for clinical application? Current Opinion in Critical Care. Dec 2010 16(6): 523–525
Ultrasound for ICP. Occasionally, (meningitis, trauma, liver failure, strokes) we wonder what the pressure inside the head is. CTs of course, let us peek inside but only allow inferences. Sometimes, we wonder so much about ICP that we have the brain surgeons put an invasive monitor thru the skull. That's nice because it can also be therapeutic (in the case of EVDs). But is there a quicker way? Yes! Does it work? Maybe!
In 2010, when someone asks the question, 'is there a quicker way' the correct answer is either Epic or Ultrasound. Ultrasound? Sure. Recall that the optic nerve is sheathed within the dura. It appears that elevated pressures allow CSF buildup in this semi-compliant sheath and widen the diameter. (That's also the basis for blathering on about papilloedema). Multiple studies have measured the diameter of the optic sheath with ultrasound (at a standardized location, 3mm past the globe) and found a nice concordance with ICP. On study found a diameter greater than 5 (normal=3mm) was strongly predictive of an of ICP >20 mm Hg (sensitivity and specificity 94% and 76%, respectively).
Further work with MRI looking at the optic nerve sheath has shown that it is even more sensitive. With MRI, a cut-off value of 5.30 mm yields a sensitivity of 100% for diagnosis an ICP greater than 20.
Soldatos T. Optic nerve sonography: a new window for the non-invasive evaluation of intracranial pressure in brain injury. Emerg Med J 2009;26:630-634
Geeraerts T, et al. Use of T2-weighted magnetic resonance imaging of the optic nerve sheath to detect raised intracranial pressure. Crit Care 2008;12(5):R114. Epub 2008 Sep 11.