Methodological Problems

The concentration of albumin in the urine can be assayed using a number of immunoassays [20]. The major problem is the day to day variation of 23 to 52 %.

This variation is similar regardless of the urine collection procedure used: 24h, overnight collection, timed collection at daytime, during water diureses or by calculating an albumin/creatinine-ratio [4,20,22,59]. It is therefore recommended that presence of microalbuminuria is confirmed in at least two more urine collections [58].

Table 1. Four prospective studies demonstrating that an increased urinary albumin excretion rate (UAER) is a predictor of nephropathy in IDDM patients.

Number of patients Method for collecting urine UAER

Predictive Value for nephropathy (^g/min) Observation (years)

Number of patients with UAER above the predictive value who progressed to nephropathy

Gentofte London Aarhus Gentofte 2

23 63 44 71

24 hours 24 hours

Gentofte London Aarhus Gentofte 2

23 63 44 71

24 hours 24 hours

30

30

15

70

6

14

10

6

5/8

7/8

12/14

7/7

*) The patients from this study were also included as a part of Gentofte 2.

The UAER is increased in the presence of urinary tract infections, menstrual bleedings, nephrological diseases other than diabetic nephropathy, severe hypertension and severe cardiac disease which all have to be excluded. It is also elevated during heavy physical exercise but not significantly affected in healthy subjects during normal daily life activities [20,22]. The UAER is elevated in diabetic patients in very poor glycaemic control with ketonuria and during episodes of ketoacidoses [20].

The collection period is also of importance. The level is similar in urines collected over 24-h and in timed daytime urine collections but reduced by 25% in urines collected overnight. Therefore the range of microalbuminuria in overnight urines should be an UAER of 23 to 230 mg/24h (15 to 150 ^g/min) [20].

A close time-relationship between increase in UAER and increase in blood pressure has been demonstrated (60). The increase in UAER may precede the increase in blood pressure [61].

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