What is the albumin (Albumin) to creatinine (Creatinine) ratio when the albumin in the urine is less than 3 milligrams per liter (mg/L)?

From the Guidelines

No, you cannot calculate the albumin to creatinine ratio (ACR) when the albumin in the urine is reported as <3mg/L because this is below the detection limit of the test. The ACR requires both a specific albumin value and a creatinine value to calculate the ratio. When albumin is reported as less than a certain threshold (in this case <3mg/L), it means the actual concentration is too low to be accurately measured by the laboratory method used. For a proper ACR calculation, you would need both a quantifiable albumin concentration and the urine creatinine concentration.

Key Points to Consider

• According to the KDIGO 2012 CKD guideline 1, albuminuria categories are assigned based on the albumin-to-creatinine ratio (ACR), with Category A1 being <3 mg/mmol, which corresponds to normal to mildly increased albuminuria.
• The guideline also notes that where albuminuria measurement is not available, urine reagent strip results can be substituted, but this does not apply in cases where the albumin level is below the detection limit.
• A more recent study published in 2022 1 reiterates the importance of albuminuria categories in classifying CKD, but does not provide guidance on calculating ACR when albumin levels are below the detection limit.
• Generally, an undetectable albumin level suggests normal kidney function with respect to protein filtration, as healthy kidneys should prevent significant albumin from appearing in the urine.
• If clinical suspicion for kidney disease remains despite this low albumin result, more sensitive testing methods or repeated testing might be warranted.

From the Research

Calculating Albumin to Creatinine Ratio

• The albumin to creatinine ratio (uACR) is a screening assay for chronic kidney disease (CKD) 2.
• A value of >30 mg/g is flagged abnormal, but lower ratios have prognostic implications 2.
• To calculate the uACR, the urine albumin (uAlb) should be measurable to 3 mg/L to match the lowest creatinine concentration generally utilized (10 mg/dL) 2.
• If the albumin in the urine is <3mg/L, it may still be possible to calculate the uACR, but the result may not be accurate due to the limitations of the measurement methods 3.
• The uACR can be calculated using a spot urine sample, and the result can be used to identify and monitor disease trajectory in cardiovascular, kidney, and metabolic conditions 4.

Measurement Methods

• The main methods of determination of albumin in the urine are immuno-turbidimetric and immuno-nephelometric methods, high performance liquid chromatography with steric exclusion, and liquid chromatography coupled with mass spectrometry 3.
• Immunoanalysis techniques are the most used, but they are not standardized, and large bias can be found between the different kits 3.
• The assay used to measure uAlb should be linear to 1.6 mg/L, and interday precision at 3.7 mg/L and 4.3 mg/L should be 7.7% and 8.6%, respectively 2.

Clinical Implications

• Albuminuria is an important risk marker for adverse cardiovascular and renal outcomes and mortality 5.
• The relationship between albuminuria and risk is continuous and linear, like that of blood pressure and cardiovascular risk 5.
• Routine annual screening can detect changes in urine albumin excretion and improve the timely identification of albuminuria, and therefore should be considered in patients with diabetes, hypertension, and chronic kidney disease 5.
• The uACR demonstrates a high degree of within-individual variability among individuals with type 2 diabetes, and multiple urine collections for UACR may improve capacity to monitor changes over time in clinical and research settings 6.