Current Questions on Proteinuria and Albuminuria

Introduction

Proteinuria is a classic sign of kidney disease, which was considered as a marker of progressive kidney disease, whereas microalbuminuria was established first as an early sign that predicts overt proteinuria in diabetic nephropathy. Later, several evidence proved that pathological “albumin-leakage” appears not only in diabetes but also means an increased risk for further vascular complications in all types of cardiovascular diseases reflecting widespread endothelial dysfunction.^1–4 Albuminuria is probably due to damage of the glomerular endothelial cell glycocalyx and/or the glomerular podocytes caused by local or systemic factors such as inflammatory mediators, glycemic products, free radicals, and others.⁵ Nowadays, microalbuminuria is mainly recognized as a cardiovascular risk factor, with no lower limit.⁶ According to the latest clinical studies, detection of albuminuria and proteinuria is suggested not only for monitoring of diabetic nephropathy but these laboratory test are necessary in all cases when early cardiovascular complications may develop.^7,8 Even though the above normal urinary albumin level predicts the development of micro- and macroalbuminuria, a higher baseline means higher mortality later.⁹ Above this, there is no doubt that albuminuria is a good marker of progression of kidney disease, whereas proteinuria reflects increased cardiovascular morbidity and mortality also. Decreased albuminuria or proteinuria resulted in decreased risk for both cardiovascular events and end-stage kidney disease.

Abstract

According to current clinical trials, albumin excretion not only indicates kidney damage but it is also a risk factor for the progression of kidney disease and future cardiovascular events. While proteinuria is considered as a marker of kidney function, microalbuminuria, first of all, indicates cardiovascular risk. Sensitivity of the laboratory tests is method dependent, some of the previously used tests do not meet the clinical requirements, and the error of urine collection makes the results misleading. To avoid these preanalytical problems, recent guidelines suggest the calculation of albumin and creatinine ratio (ACR) and protein and creatinine ratio (PCR) from the values measured from the first morning urine, as these ratios correlate well with the corresponding results of properly collected 24-hour urine. For the clinical diagnosis of albuminuria, the sensitive immunoturbidimetric assays are recommended. Because of poor sensitivity, urinary albumin dipsticks are not recommended for the measurement of albuminuria. For the diagnosis of proteinuria, wide-range urinary protein reagents are available with high sensitivity. The traceability of calibrator to a reference material is a critical requirement. For these reasons, proteinuria and albuminuria of a patient should be monitored in the same laboratory, using a fixed method and cut-off value. Protein, albumin, and creatinine should be measured from the same urine sample, practically using the same analyzer. The ACR values should be reported together with gender-dependent reference ranges. As the PCR range is wider, the same cut-off value can be used for men and women. We discuss the interpretation and diagnostic algorithm of proteinuria and albuminuria.

Keywords

ACR, albuminuria, cardiovascular disease, chronic kidney disease, proteinuria, protein/creatinine