Accurate measurement of albuminuria at reduced cost

Sir,

Screening for albuminuria is important for early detection of renal involvement in diabetes [1]. Because of considerable day-day variation in albumin excretion, the median result of three overnight or first morning collections is taken when accurate diagnosis is needed [2]. Measuring urinary albumin creatinine ratio (ACR) corrects for inaccuracies in timing of collections and dilutional effects [3]. If ACR measured on a single mixed sample of equal-sized aliquots taken from each of the three collections could provide results of similar accuracy to the median value of ACR from three separate collections, accurate measurement of ACR might be obtained at lower cost.

For 1 month all triplicate collections for ACR from our clinic were analysed by both methods. The samples were collected on alternate nights from 29 patients with ACR ranging from 0.3 to 44.8 g/mol, stored at room temperature and brought directly to the laboratory. Samples were analysed within 6 days of collection and confirmed negative for nitrites (Nephur 6 test strips). After mixing thoroughly, a 2.0 ml aliquot was taken from each collection and assayed separately. The median of the three measurements was calculated (ACR Med). A second 2-ml aliquot was taken from each sample and the three aliquots mixed together to form a 6.0 ml mixed sample (ACR Mix), which was then assayed for ACR. The three single samples and the mixed sample were analysed in a single run using immunoturbidimetry [4] (Roche Diagnostics, Basel, Switzerland). Intra-assay coefficients of variation were 4.8% for albumin and 2.9% for creatinine. Analyses were performed on log-transformed data. The geometric mean (interquartile range) for ACR Med was 6.2 (2.8–20.3) vs 5.6 g/mol (2.8–20.5) for ACR Mix (not significant on paired t-test). Correlation between the two measurements was highly significant (r = 0.93, P<0.001). Figure 1 shows the difference between the two measures of ACR against their mean [5]. The mean (±2 SD) of the means of the differences between the two measures of albuminuria was 0.14 g/mol (±2.9 g/mol) indicating a high degree of agreement, which appeared constant over the whole range of albuminuria.



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Fig. 1. Limits of agreement (mean±2 SD) between ACR Med and ACR Mix.

 
Using ACR over 3 g/mol to indicate microalbuminuria and ACR Med as the ‘gold standard’ the positive predictive value of ACR Mix was (20/21) 95.2% and the negative predictive value was (7/8) 87.5% (Table 1). There was only one false negative and one false positive detection of microalbuminuria using ACR Mix.


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Table 1. Predictive value of ACR Mix

 
These preliminary findings suggest that for ACR ranging from normoalbuminuria to proteinuria, mixing equal aliquots of urine from each of three collections to produce a single sample for measurement is as useful as measuring each sample separately and taking a median value. Mixing three aliquots of urine from separate overnight collections requires no more laboratory time than measuring three aliquots separately. The cost of measuring ACR by this new method is reduced in our laboratory from £21.45 to approximately £7.15 representing a considerable saving of laboratory time and clinical resources.

Conflict of interest statement. None declared.

Mike Krimholtz, Andrew Smith and GianCarlo Viberti

Department of Diabetes, Endocrinology and Internal Medicine Guy's Campus Kings College London London UK Email: mike{at}krimholtz.com

References

  1. Almdal T, Norgaard K, Feldt-Ramussen B, Deckert T. The predictive value of microalbuminuria in IDDM. A five year follow up study. Diabetes Care 1994; 17: 120–125[Abstract]
  2. Chachati A, von Frenckell R, Foidart-Willems J, Godon JP, Lefebvre PJ. Variability of albumin excretion in insulin-dependent diabetics. Diabetic Med 1987; 4: 441–445[ISI][Medline]
  3. Gatling W, Knight C, Hill RD. Screening for early diabetic nephropathy: which sample to detect microalbuminuria? Diabetic Med 1985; 2: 451–455[ISI][Medline]
  4. Swaminathan R, Cheung CK. Rapid, economical immunoturbidimetric method for albuminuria. Clin Chem 1987; 33: 204–205[Free Full Text]
  5. Bland MB, Altman DG. Statistical methods for assessing agreement between two methods of clinical measurement. Lancet 1986; 1: 307–310[ISI][Medline]




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