Renal function (GFR or creatinine clearance) as estimated by serum creatinine and 24-hour urine collection should in theory closely correlate.
However, I have run into a case where they differ greatly. The serum creatinine was measured twice at two separate labs and were in normal range at 0.89 and 1.0 mg/dL, yielding a calculated CrCl of 115 and approx 90. However, the 24-hour urine creatinine clearance results yielded 38 ml/min and 5 ml/min, which would be either acute kidney injury / acute renal failure, or chronic kidney disease / failure (CKD stage 3b and CKD stage 5 respectively). The test was again repeated a third time and again resulted in 1.0mg/dl but this time a CrCl 70 mg/dl.
This is a huge difference with large ramifications in terms of diagnosis and treatment. The question is:
What could be the reason for this, and which measurement is the more reliable one?
I've read several studies that concluded that the serum creatinine alone was actually a better predictor of GFR than urine creatine clearance over 24, 4, and 2h. Every cohort study I found online shows an upper margin of error of around 30% where predicted values from serum creatinine fall and measured clearance levels.
There are various factors at play here:
The GFR to serum creatinine is a hyperbolic relation which is a bad function for estimating values greater than 60 ml/min and even as low as 45 ml/min: ]1 As you can see the entire range of values for GFR is estimated over a small fraction of .5 mg/dl difference whereas values lower than 30 range over 20 mg/dl serum creatinine.
The jaffe assay which was used reacts creatinine with picric acid in alkaline solution and spectrophotometrically compared to a baseline creatinine sample with are both measured against a blank. This particular reaction is not as precise as the less common enzymatic assay which does not react with with nonspecific targets
"The nonspecificity of Jaffe's reaction causes falsely elevated creatinine results in the presence of protein, glucose, acetoacetate, ascorbic acid, guanidine, acetone, cephalosporins, aminoglycosides (mainly streptomycin), ketone bodies, α-keto acids, and other organic compounds." -wiki
- The standardization of measurements within labs and between labs was found to introduce about 5% error(and in 1 sample 25%) when 5 samples over the entire GFR range were sent to 26 different instruments:
After reading many studies online it appears the estimated GFR calculated by formulas are rather inaccurate predictors of GFR, and the creatine clearance is a rather imprecise measurement as well. Here's one study showing standard errors that span 100% when comparing calculated vs measured gfr although it suffers from having only 100 subjects: One large cohort study of 45000 has good news for young healthy individuals with low creatinine clearance values: The lower the value the slower the decline with age so that even at the lowest 2.5% of 70Ml your average projection is not kidney failure 40 years later: