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 alpha(1)-microglobulin-to-creatinine ratio in 10 of the 27 discrepant samples analysed, four of which also had a raised beta-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.