Investigation of apparent non-albuminuric proteinuria in a primary care population.

BACKGROUND: There is debate as to whether using the urinary albumin- or protein-to-creatinine ratio (ACR or PCR) should be the primary test for proteinuria. Whilst albuminuria (increased ACR) in the absence of proteinuria (increased PCR) may be expected in some patients, the converse (i.e., proteinuria in the absence of albuminuria) is more unusual and its cause and significance are unclear. We investigated the nature of such apparent non-albuminuric proteinuria in a primary care population of patients. METHODS: ACR and PCR were measured in 569 urine samples from patients who either had chronic kidney disease or were at increased risk of the condition. Samples with apparent proteinuria (PCR ≥23 mg/mmol/≥200 mg/g) but no albuminuria (ACR <3.4 mg/mmol/<30 mg/g) were classified as 'discrepant' (37% of proteinuric samples, 6% of all samples); 27 of these samples were available for further analyses. The further analyses included electrophoresis, repeat measurement, immunoassays for markers of tubular proteinuria and use of alternative albumin and total protein methods. RESULTS: Electrophoresis did not identify significant proteinuria in the discrepant samples. The only evidence of tubular proteinuria following measurement of three urinary markers of the condition was a mildly increased α1-microglobulin-to-creatinine ratio in 10 of the 27 discrepant samples analysed, four of which also had a raised ß-trace protein-to-creatinine ratio. Use of an alternative urinary total protein method resulted in significantly lower PCRs and 17 of the 27 samples were no longer classified as proteinuric. CONCLUSIONS: We were unable to confirm the cause of a raised PCR without albuminuria in these patients and suspect that in most cases it is artefactual.

The diagnostic accuracy of a urine albumin-creatinine ratio point-of-care test for detection of albuminuria in primary care.

BACKGROUND: Albuminuria is an important sign of chronic kidney disease and is detected routinely by measurement of urinary albumin-creatinine ratio (ACR). A Siemens CLINITEK test designed for use at the point of care is available that can semiquantitatively measure ACR. STUDY DESIGN: Diagnostic accuracy study evaluating a urinary ACR point-of-care test. SETTING & PARTICIPANTS: The semiquantitative ACR test was evaluated at the point of care in a representative primary care population (those with or at increased risk of chronic kidney disease) of 642 patients under standard operational conditions and compared with the reference standard of ACR measurement in the clinical laboratory. INDEX TEST: The point-of-care CLINITEK semiquantitative ACR test. This test uses dye-binding and catalytic assays for albumin and creatinine, respectively, on a Microalbumin 9 strip, which is read by the CLINITEK Status Analyzer, and ACR is calculated automatically. REFERENCE TEST: Laboratory measurement of albumin and creatinine on an Abbott Architect analyzer by immunoturbidimetric and enzymatic assays, respectively, and calculation of ACR. RESULTS: The prevalence of albuminuria (laboratory ACR≥30 mg/g) in the study population was 20.2%. Sensitivity and specificity of the point-of-care test for detecting albuminuria were 83.2% and 80.0%, respectively. Positive and negative predictive values were 51.2% and 95.0%, respectively; positive and negative likelihood ratios were 4.16 and 0.21, respectively. Twenty-three (3.6%) samples measured at the point of care were not analyzed in the central laboratory for a variety of reasons, including laboratory reception data entry errors. LIMITATIONS: Our sensitivity calculation is accurate to an approximately 8% CI. CONCLUSIONS: The instrument-read reagent strip test was a poor rule-in test for albuminuria at the point of care, as evidenced by the low positive predictive value, but was a reasonable rule-out test. Observed sensitivity was lower than reported in earlier laboratory-based studies. This decreased diagnostic accuracy needs to be balanced against the potential advantages of a point-of-care testing approach.