Protein creatinine ratio

To circumvent the practical difficulties of collecting 24 h urine specimens and the limitations of urinary dipstick measurements, researchers have investigated the use of the protein: creatinine ratio on a spot urine specimen. This should not be confused with an albumin (measured by immunoassay) : creatinine ratio which has not been shown to be of value in testing for proteinuria associated with hypertensive disorders of pregnancy.

Most (Jaschevatzky et al., 1990; Neithardt et al., 2002; Ramos etal., 1999; Robert etal., 1997; Saudan et al., 1997), but not all (Durnwald and Mercer, 2003; Rodriguez-Thompson and Lieberman, 2001), studies have reported a good correlation (r = 0.92—0.94) between a spot protein: creatinine ratio and the 24 h urinary protein. However, only a few studies are appropriately designed to evaluate the usefulness of a protein : creatinine ratio as a screening/diagnostic test for significant proteinuria (24 h protein >0.3 g) in hypertensive disorders of pregnancy and both are relatively underpowered (Durnwald and Mercer, 2003; Saudan etal., 1997). In the first study of a hundred women seen because of hypertensive problems in pregnancy, a spot urinary protein: creatinine ratio was compared with 24 h urinary protein (abnormal >0.3g24h~1) (Saudan et al., 1997). Using a cut-off value of 30mgmmol~1 for an abnormal protein: creatinine ratio, sensitivity was 93%, specificity 95%, and positive predictive value 95% with a negative predictive value of 90%. None of the false negatives had a 24 h urinary protein greater than 0.4 g. The conclusion from this study was this method could be used to rapidly screen hypertensive pregnant women for proteinuria. A recent study of 220 women evaluated for suspected pre-eclampsia has found the ratio did not perform as well as this, although they used a different method to measure proteinuria (biuret reaction rather than the benzethonium chloride turbidometric method used by Saudan and co-workers) (Durnwald and Mercer, 2003). Using a cut-off of 300mgg^1 (equivalent to approximately 34mgmmol~1) to define an abnormal protein : creatinine ratio, they reported a sensitivity of 81%, specificity 56%, positive predictive value of 86% and a negative predictive value of 48%. In other words, 19% of women with significant proteinuria on a 24 h urine were not detected by a protein : creatinine ratio, the majority of women with a positive test do have significant proteinuria but half the women with a negative protein : creatinine ratio result had significant proteinuria. Overall the protein: creatinine ratio with a 300 mg g_1 cut-off correctly categorized 75% of women with respect to proteinuria being present or absent. From the ROC analysis data, if a lower cut-off (200 mgg-1) was used then sensitivity increased to 91%, specificity remained low at 48% and 39% of women with a normal protein : creatinine ratio had significant proteinuria on a 24 h urine. At this lower cut-off value, overall 80% of women were correctly categorized as having or not having proteinuria.

In summary, a protein: creatinine ratio is probably a more accurate method to screen for proteinuria than urinary dipstick, particularly at "1+", and possibly "2+" on dipstick. In the setting of gestational hypertension with either a negative, trace or "1+" on dipstick, then a spot 24 h urine protein: creatinine ratio may be a helpful screening test to identify those women with and without proteinuria. If proteinuria is ">3+" on dipstick, the rate of false positive tests is so low that the protein : creatinine adds little as a screening test and protein excretion should be quantified directly on a 24 h specimen. The protein : creatinine ratio has not been found to be an accurate method of quantifying protein excretion and should not be used to track progression of proteinuria in preeclampsia. Centers will need to evaluate local performance of the protein : creatinine ratio, as performance may be influenced by their patient population and the method of measuring protein. Further research is required to refine the role of a protein : creatinine ratio in the management of women with gestational hypertension and pre-eclampsia. At present it should not replace the 24 h urinary protein as the definitive test to determine whether a woman has significant proteinuria.

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