The two kidneys filter approximately 650 mL of plasma every minute. This means that 37, 000 grams of albumin pass through the glomeruli each day. Only 1.3 grams, or 0.004%, of the total albumin leaks through the glomeruli, which is an amazing efficiency for any filtration system. Ninety nine percent of the leaked albumin is degraded to fragments by the renal proximal tubules, resulting in a daily urinary excretion of only ~15 mg of albumin.

The two most important laboratory tests for chronic kidney disease (CKD) are estimated glomerular filtration rate (eGFR) and urine albumin. For many people, albuminuria is the earliest sign of CKD. The 2012 clinical practice guidelines developed by the Kidney Disease Improving Global Outcomes (KDIGO) Chronic Kidney Disease Work Group include an increased role for measurement of albuminuria in the evaluation and management of CKD (Kidney International Supplements 2013, 3:19-62). Measurement of urinary albumin is preferred over measurement of total protein because it is the single most important protein in urine. Also, analytical methods for albumin have been standardized and have better accuracy and precision at the lower threshold for early CKD. Normal values of urine albumin are usually expressed as the albumin excretion rate (AER). KDIGO chose a urinary AER of ?30 mg per 24 hours sustained for >3 months as the threshold for chronic kidney disease. This value is three times higher than the normal value in young adult men and women.

Although the reference point remains an accurately timed 24 hour specimen, inaccuracies in collection often contribute to errors in estimation of protein loss. For this reason KDIGO recommends collection of an early morning urine sample. Because hydration status and urine flow rate can influence albumin concentration in a random urine sample, KDIGO recommends that laboratories report the ratio of albumin to creatinine (ACR). Creatinine excretion is fairly constant throughout the day and corrects for variations in urine concentration. An ACR value of ?30 ug/mg in a random urine sample is equivalent to an AER of ?30 mg per 24 hours.






<30 mg/24 hours

<30 ug/mg


30-300 mg/24 h

30-300 ug/mg


>300 mg/24 h

>300 ug/mg


ACR is calculated with the folllowing formula:

ug albumin/mg creatinine = microalbumin (mg/dL) x 1000/creatinine (mg/dL)

The factor of 1000 is used to convert from milligrams (mg) albumin to micrograms (ug). The units for albumin and creatinine measurements on random or timed specimens vary in clinical practice. They can be expressed as either micrograms (ug) of albumin per milligram (mg) of creatinine or milligram (mg) of albumin per gram (g) of creatinine.

Even though albuminuria is a continuous risk factor for cardiovascular and all cause mortality, KDIGO divided ACR into 3 categories to simplify clinical practice.







Normal- mild increase



Moderate increase



Severe increase


The 300 ug/mg cut-off correlates with the lower limit of sensitivity of the traditional urine dipstick for albumin. Category A3 includes the nephrotic syndrome in which albumin excretion is >2200 mg per 24 hours or an ACR of >2200 ug/mg.

KDIGO guidelines recommend at least annual measurement of GFR and albuminuria. They also provide a guide to the frequency of monitoring based on the eGFR and albuminuria categories. For example, a patient with eGFR of 40 mL/min/1.73m2 and an ACR of 200 ug/mg should be tested three times a year.

Albumin excretion also plays a role in determining the blood pressure target in patients with CKD and hypertension. For example, target blood pressure is ?140/90 in patients with an ACR <30 ug/mg and ?130/80 in patients with an ACR ?30 ug/mg.

Several studies have reported that ACR values obtained with first morning urine samples correlate more closely with the results of 24 hour urine collections than random urine samples collected later in the day. In fact random urine samples yield values that are ~50% higher than first morning samples near the decision threshold of 30 ug/mg. For this reason, KDIGO recommends measuring ACR in a first morning urine sample. However, collection of random sample is often more convenient for the patient and avoids the need for a repeat visit. If a patient has an elevated ACR on a random urine sample, KDIGO recommends repeat testing with a first morning void sample. With this sequential testing strategy, fewer than 50% of patients with an elevated ACR on a random sample will be confirmed. Repeat testing is very important to confirm a persistent increase in urinary excretion of albumin.

Daily production of creatinine can vary by a factor of two or more between patients because of differences in muscle mass. African Americans have a lower ACR than Caucasians due to increased creatinine filtration and females have a higher ACR than males for the opposite reason. KDIGO guidelines do not address these variables.  

Previous guidelines for detection of diabetic nephropathy recommended the use of different ACR thresholds for males (0-16 ug/mg) and females (0-24 ug/mg) to account for differences in creatinine excretion. However, KDIGO guidelines recommend a single threshold of 30 ug/mg should be used.

Urine samples contaminated with blood should not be submitted since albumin levels will be falsely elevated. If same day testing is not possible, urine can be stored refrigerated for two weeks without albumin degradation.

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