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Donna Myers, M.D.
02-03-2011
- Microalbuminuria is defined as an albumin to creatinine ratio (ACR) between 30 - 300 mg/g.
- Macroalbuminuria is defined as an ACR > 300 mg/g.
- Confirmation is required on 2 out of 3 samples over the next 3-6 months from initial detection in the absence of a urinary tract infection.
- Immunochemistry method offers highly sensitive and specific measure of urinary albumin either from a 24 hour collection or a randomly voided ("spot") sample.
- Immunoassays for urine albumin utilize an antibody to human albumin. The antibody-albumin complexes are measured if albumin is present.
- 4 methods to measure antibody to human albumin complexes: (1) turbidimetric analyzer, simple to perform but greater up-front expense; (2) radioimmunoassay (RIA); (3) ELISA assay, more labor intensive; and (4) radioimmunodiffusion.
- Immunoturbidimetric Analysis (ITA) is available for commercial use. One example, "The Albumin Tina-Quant" (Roche) has as its primary linearity urine albumin levels from 3 - 400 mg/L with an extended linearity to 4400 mg/L. Values > 4400 mg/L may be estimated by using dilutions up to 20-fold.
- High performance liquid chromatography (HPLC) accurately measures urine albumin but is time-consuming and limited to research studies.
- Spectrophotometric assays measuring a colored end-product are used for 24 hour urine total protein (vs. albumin) collections.
- Point-of-care testing utilizing table top immunoturbidimetric reactions such as the DCA2000 (Bayer analyzer) and the HemoCue Albumin 201 system has been proposed for a rapid turn-about of results (7 minutes).
- On routine urinalysis protein is detected by a reagent stick with tetrabromophenol. Albumin combines with the blue divalent anionic form of the indicator changing color from yellow to green to blue. A colorimetric analyzer (reflectance spectroscopy) is used; it has a sensitivity of 10 mg/dL with a specificity of 97%. A correction pad compensates for the natural color of urine.
- A technician-dependent spot urine protein by dipstick is a useful tool in a clinic practice.
- Sulfosalicylic acid 3% turbidity test offers a semi-quantitative estimate of total urinary protein, measuring albumin, globulins and Bence Jones proteins. It is most useful in making a preliminary diagnosis of nephrotic range proteinuria, dramatically demonstrated by thick white clumps in the test tube.
- Guidelines recommend annual screening for chronic kidney disease starting from the diagnosis of type 2 diabetes (T2DM) and starting 5 years after the diagnosis of type 1 diabetes (T1DM).
- Screening for kidney disease should consist of a serum creatinine with estimation of glomerular filtration rate (GFR) and a spot urinary albumin:creatinine ratio (ACR).
- A 24 hour urine collection for protein is seldom needed.
- In patients with diabetes and hypertension, both low levels (microalbuminuria) and high levels (macroalbuminuria in nephrotic range) of urinary protein is also a risk predictor of heart failure in addition to nephropathy.
- In the general population, microalbuminuria increases the chance of developing hypertension, diabetes and cardiovascular disease. It should be part of a comprehensive cardiovascular risk profile for healthy individuals.
- In patients with diabetes or a history of cardiovascular disease, microalbuminuria increases the risk of developing heart failure almost 2-fold.
- High macroalbuminuria (> 3 g/g creatinine) in T2DM is associated with a 3-fold higher risk of heart failure vs. those with lower levels of macroalbuminuria (< 1.5 g/g).
- Point-of-care testing provides immediate results during consultation, offers an added risk assessment for cardiovascular disease, and allows physicians to motivate patients to make appropriate life style changes at the time of the clinic visit.
- High levels of conjugated bilirubin (> 66 mg/dL), hemolysis (> 300 mg/dL) and hyperlipidemia interfere with the Albumin Tina-Quant assay, with results flagged or not reported in presence of these interfering substances.
- Interference with the Tina-Quant assay also from very high levels of urinary acetone, ascorbic acid, calcium, creatinine, glucose, hemoglobin and urea and uric acid.
- Patients with uric acid kidney stones may be hyperuricosuric (> 800 mg/day in males), interfering with the assay with up to 10% inaccuracy on the Tina-Quant assay.
- Do point of care testing for microalbuminuria only when negative for leukocytes, nitrites and blood.
- Measurements of urinary protein by assays sensitive only to albumin excludes measurement of other tubular proteins such as Bence Jones protein, missing the diagnosis of multiple myeloma.
- The colorimetric dipstick analysis for protein is semi-quantitative; has greater sensitivity to albumin than to Bence Jones proteins and globulins; requires a fresh specimen (refrigerated < 4 hrs); and may give a false positive in the presence of alkaline urine (pH > 8), hemoglobin, and contrast medium.
- Another limitation to the dipstick analysis is inter-observer variability.
- Collection of a 24 hour urine is cumbersome and not generally used, requiring strict adherence to instructions, adequate hydration, and voiding that is both timely and complete. Useful in measuring urine creatinine as this is stable for a given patient unless body mass changes.
- The measurement of urinary albumin is critical to identification of early diabetic nephropathy. Microalbuminuria is relatively specific in type 1 diabetes, although not nearly as specific to diabetic nephropathy in type 2 diabetes.
- A spot urine albumin to creatinine ratio is recommended for detecting albuminuria.
- Both micro- and macroalbuminuria are associated with a higher risk of cardiovascular disease in normal and at-risk populations.
- The reason for the link between albuminuria and cardiovascular disease is unclear, but may be due to impaired systemic endothelial function.
- Albuminuria is an important therapeutic target for renal and cardiovascular protection.
- KDOQI;
KDOQI Clinical Practice Guidelines and Clinical Practice Recommendations for Diabetes and Chronic Kidney Disease.;
Am J Kidney Dis;
2007; Vol.
49; pp.
S12-154;
ISSN:
1523-6838;
PUBMED: 17276798
Rating:
Basis for recommendation
Comments:Comprehensive practice guidelines for diabetes and chronic kidney disease by the National Kidney Foundation - Kidney Disease Outcomes Quality Initiative (NFK-KDOQI).
- Arnlöv J, Evans JC, Meigs JB, et al.;
Low-grade albuminuria and incidence of cardiovascular disease events in nonhypertensive and nondiabetic individuals: the Framingham Heart Study.;
Circulation;
2005; Vol.
112; pp.
969-75;
ISSN:
1524-4539;
PUBMED: 16087792
Rating:
Basis for recommendation
Comments:Urinary albumin:creatinine ratios below normal (< 30 mg/g) predicted the development of de-novo cardiovascular disease in a population healthy at baseline.
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