David Levy, MD, FRCP
Quantification of Urinary Albumin Excretion
The following methods are in current use:
- Spot early-morning urine specimen expressed as ACR (mg/mmol or mg/g): albumin excretion corrected for urine output;
- 24-hour urinary albumin excretion (mg per 24 hours);
- Timed (usually overnight) AER (µg/min);
- Urinary albumin concentration uncorrected for creatinine (i.e. mg/L).
ACR is widely used as a screening test, and increasingly to monitor response to treatment, on account of its simplicity for both the patient and the laboratory. Reliable point-of-care methods for measuring ACR are now available (e.g. DCA Vantage). Urinary albumin concentration in a spot specimen (point-of-care HemoCue Albumin 201) has its advocates, but so far has not been widely adopted. Although ACR correlates well with 24-hour urinary albumin excretion, there are difficulties with its universal adoption .
- Its definition is not agreed worldwide (see below): the original definitions of microalbuminuria and macroalbuminuria were based on 24-hour collections.
- The lower limits for microalbuminuria defined by ACR are higher in females than males (24-hour urinary creatinine excretion is lower in females).
- 24-Hour urinary creatinine measurement falls with age, especially in females. ACR increases with age, and for precision, age- and sex-adjusted values should be used.
- Early-morning (first pass) specimens should always be analysed….
Factors that may falsely increase urinary albumin excretion include the following:
- Strenuous exercise can increase ACR in normal people to 6–8 mg/mmol (53–70 mg/g), but it settles to baseline within 24 hours.
- Fever/systemic infection.
- Very poor glycemic control leading to hyperfiltration.
- Contrary to widespread belief, asymptomatic UTI (see Chapter 7) does not cause proteinuria or microalbuminuria. Management of albuminuria should not be delayed on account of bacteriuria.
Urinary albumin versus protein measurements
Because of the significance of microalbuminuria in diabetes practice it is usual to measure urinary albumin; once patients transfer to the renal team, the degree of proteinuria is less of a concern, and in any case gram, rather than milligram, protein leakages are the rule. Renal units therefore often use protein/creatinine ratios. Albumin constitutes about 70% of total urinary protein; the distinction is of importance in the microalbuminuric range.
Reference ranges for albumin excretion (Table 8.2) Normoalbuminuria
The normal range for AER is usually quoted as 1.5–20 µg/min, with a geometric mean of 6.5 µg/min, approximately equivalent to 10 mg per 24 hours (AER is logarithmically, not normally distributed). This value is similar to the detection limit of most laboratory assays. ACR in healthy volunteers and in non-microalbuminuric type 2 patients is about 0.4 mg/mmol (males) and 0.5 mg/mmol (females).
Microalbuminuria is defined as:
- urinary albumin excretion 30–299 mg per 24 hours;
- AER 20–199 µg/min;
- ACR 2.5/3.5 to 20 mg/mmol (USA 30–299 mg/g);
- there may be intermittent stick-positive proteinuria.
The threshold for microalbuminuria using ACR is higher in females than males. In the UK threshold values are usually quoted as 2.5 mg/mmol (22 mg/g) or more in males, and 3.5 mg/mmol (31 mg/g) or more in females, though 2.0 and 2.8, respectively, are also used, for example in Canada. Using a factor of 8.8 for conversion of SI to traditional units, the range defining microalbuminuria is not the same in the UK and in the USA; agreement is needed. The classic clinical trials used different definitions for microalbuminuria (e.g. DCCT > 40 mg per 24 hours; UKPDS > 50 mg/L).