NDT Advance Access published November 17, 2008

Nephrol Dial Transplant (2008) 1 of 4

doi: 10.1093/ndt/gfn629

Original Article

Does bacteriuria interfere with albuminuria measurements of patients

with diabetes?
Caroline K. Kramer1 , Joza Camargo2 , Eliza D. Ricardo1 , Fernando K. Almeida1 , Lus H. Canani1 ,
Jorge L. Gross1 and Mirela J. Azevedo1
Endocrine Division, Hospital de Clnicas de Porto Alegre, Universidade Federal do Rio Grande do Sul and 2 Clinical Pathology
Division, Hospital de Clnicas de Porto Alegre, Porto Alegre, Brazil

Abstract
Background. Urinary albumin is the main parameter employed to diagnose diabetic nephropathy (DN). The exclusion of bacteriuria has been recommended at the time of DN
diagnosis. This approach has been debated and information
on this suggestion in patients with diabetes is scarce. The
present case-control study was conducted to investigate the
interference of bacteriuria in the interpretation of urinary
albumin measurements in random urine samples of diabetic
patients.
Methods. Urinary albumin concentration (UAC) was measured in random urine samples twice in diabetic patients with and without bacteriuria (105 colony-forming
units/mL). Cases (n = 81) were defined as patients who
had baseline UAC measurement in the presence of bacteriuria and had the second UAC measured in a sterile urine
sample. Controls (n = 80) had the two UAC measured in
sterile urine specimens.
Results. Baseline UAC was not different between case
[15.4 (1.52148) mg/L] and control groups [14.2 (1.5
1292) mg/L; P = 0.24], nor was the proportion of patients
with normo-, micro- and macroalbuminuria. In cases, UAC
measurements in the presence of bacteriuria and in sterile
urine specimens were not different [15.4 (1.52148) versus
13.7 (1.52968) mg/L; P = 0.14)], nor was the proportion
of normo- (51.9% versus 61.5%), micro- (40.7% versus
32.1%) and macroalbuminuria (7.4% versus 6.4%; P =
0.46). In the control group, UAC values were also not different in the two urine samples: [14.2 (1.51292) versus 9.7
(1.51049) mg/L, P = 0.22].
Conclusions. The presence of bacteriuria does not interfere
significantly with urinary albumin measurements and its
exclusion is not necessary to diagnose DN.
Keywords: albuminuria; bacteriuria; diabetic
nephropathy
Correspondence and offprint requests to: Caroline K. Kramer, Servico
de Endocrinologia do Hospital de Clnicas de Porto Alegre, Rua
Ramiro Barcelos 2350, Predio 12, 4 andar, 90035-003 Porto AlegreRS, Brazil. Tel: +55-51-2101-8127; Fax: +55-51-2101-8777; E-mail:
ckkramer@terra.com.br

Introduction
Urinary albumin measurement is the main marker employed
to diagnose diabetic nephropathy (DN) [1], and increased
values are considered a risk factor for DN progression and
cardiovascular events [24]. The presence of bacteriuria has
been suggested as a factor that might interfere in urinary
albumin measurements [5], and therefore, it has been recommended that urinary albumin should be measured only
in sterile urine for the proper diagnosis of DN [68]. However, data to support this recommendation, especially in
patients with diabetes (DM), are scarce.
The preferred urine sample for DN diagnosis is a random urine spot according to the American Diabetes Association [9] and the National Kidney Foundation [10]. The
measurement of urinary albumin concentration (UAC) in a
random urine specimen seems to be the best choice for the
diagnosis of microalbuminuria in diabetic patients, considering its cost and accuracy [11]. In this context, there is
no information regarding the role of bacteriuria influence
in UAC measurements in patients with diabetes. Therefore,
this study was performed to investigate the possible interference of bacteriuria in the interpretation of urinary albumin
measurements in random urine samples in diabetic patients.

Subjects and methods

Subjects
Type 2 DM patients [12] who had UAC measurements performed twice in random urine specimens concurrently with
urine cultures were identified from the Clinical Pathology
Laboratory database (December 2006 to December 2007).
From the initial 1814 consecutive recorded samples in the
laboratory, 703 had concurrent urine cultures. Of these,
only samples from patients who had two UAC measurements, <6 months apart, were included. Exclusion criteria
were the presence of persistent bacteriuria or urine samples from patients who had started on ACE inhibitors or
new anti-hypertensive medications between the two urine
collections.


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Consecutive diabetic patients who had the first UAC

measured in a urine sample with bacteriuria and the second UAC measurement in a sample without bacteriuria were
considered cases. The patients whose UAC was measured in
the two consecutive urine samples in the absence of bacteriuria were defined as controls. This protocol was approved
by Hospital Ethical Committee.

Methods

Statistical analyses
A sample of 80 patients in each group was estimated to
detect a difference of 10 mg/L in urinary albumin between
cases and controls, with a power of 80%. Students t-test and
chi-square tests were used as appropriate. Wilcoxons test or
MannWhitney U tests were used to compare UAC values.
Data were expressed as mean SD or median (range).
P values <0.05 were considered significant.

Table 1. Baseline clinical and laboratory characteristics of diabetic patients with and without bacteriuria
Bacteriuria

N
Male subjects, n (%)
Age (years)
Weight (kg)
Systolic blood pressure (mmHg)
Diastolic blood pressure (mmHg)
A1C test (%)
Fasting plasma glucose (mmol/L)
Total cholesterol (mmol/L)
High-density cholesterol (mmol/L)
Low-density cholesterol (mmol/L)
Triglycerides (mmol/L)
Creatinine (mol/L)
Urine specific gravity

Present

Absent

P-value

81
15 (18.5)
58.6 17.1
73.6 14.8
129.5 21
76.4 10.6
8.08 2.25
7.8 2.7
4.8 1.1
1.45 0.47
2.3 0.42
2.97 (0.920)
83.9 27.4
1016 6.3

80
25 (31.5)
56.8 16.1
75.2 13.8
129.5 19.1
76.2 13.2
7.54 1.62
7.7 3.6
4.5 1.0
1.52 0.45
2.47 1.05
3.0 (138)
76.0 15.9
1015 6.5

0.09
0.49
0.48
0.98
0.92
0.08
0.91
0.09
0.39
0.34
0.30
0.02
0.07

Data are expressed as mean SD, number of subjects with studied characteristic (%) or median (range).

The proportion of male sex, age and weight did not differ
between patients with and without bacteriuria. Also, blood
pressure levels, glucose control and lipid profile were not
different between the two groups.
UAC [median (range)] was not different between cases
[15.4 (1.52148) mg/L] and controls [14.2 (1.51292)
mg/L, P = 0.24] as well as the proportion of DN stages
(cases: normo- 51.9%, micro- 40.7% and macroalbuminuria 7.4%; controls: normo- 55%, micro- 41.3% and
macroalbuminuria 3.8%; P = 0.58).
Results from UAC measurements in the first and second urine samples are shown in Figure 1. In cases, baseline
UAC values in the presence of bacteriuria [15.4 (1.52148)
mg/L] were not different from values in sterile urine samples [13.7 (1.52968) mg/L; P = 0.14], nor was the proportion of normo- (51.9 versus 61.5%), micro- (40.7 versus
32.1%) and macroalbuminuric samples (7.4 versus 6.4%;
P = 0.46). In the control group, the UAC measurements
were also not different between the first and second urine
specimens: [14.2 (1.51292) mg/L versus 9.7 (1.51049)
mg/L, P = 0.22]. The time elapsed between the two collected urine samples was not different between cases and
control groups (data not shown). In addition, no difference
was observed between UAC changes from the first to the
second measurements both in cases [4 (607820)] and
controls [1 (571223) mg/L, P = 0.67].

Discussion
Results
One hundred sixty-one diabetic patients were studied. The
case group was formed by 81 patients (18.5% males; aged
58.6 17.1 years) and the control group by 80 patients
(31.5% males; aged 56.8 16.1 years).
Table 1 shows baseline clinical and laboratory characteristics of cases and controls. Serum creatinine was
the only laboratory data different between cases (83.9
27.4 mol/L) and controls (76.0 15.9 mol/L, P = 0.02).

This study indicated that the presence of bacteriuria did

not significantly interfere with interpretation of UAC measurements in random urine samples in diabetic patients,
since UAC values were not modified by the eradication of
bacteriuria.
Although evaluation of bacteriuria simultaneously with
urinary albumin measurement has been widely used, this
practice is still questionable [15]. The absence of interference of bacteriuria in 24-h urinary albumin excretion has

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All urine samples were collected as a midstream specimen in a sterile container and cultured for bacterial growth,
quantification and antimicrobial sensitivity. Bacteriuria
was defined as pathogen growth of 105 colony-forming
units/mL. Antimicrobial treatment was performed based
on antimicrobial sensitivity information. In the cases, eradication of bacteria was documented in the second urine
sample concurrently with UAC measurement. The urine
specific gravity was measured by a test strip (Combur-Test;
Boehringer Mannheim, UK).
Urinary albumin was measured by the immunoturbidimetric method (Microalb; Ames-Bayer, Tarrytown, NY,
USA). In our laboratory, using urine samples with the albumin concentration of 30 and 100 mg/L, the intra- and interassay CVs were both <6% [13]. Normoalbuminuria was defined as UAC <17 mg/L, microalbuminuria UAC from 17 to
174 mg/L and macroalbuminuria UAC >174 mg/L [14].
Glycated haemoglobin (A1C test) was measured by HPLC
(Merck-Hitachi 9100, Germany). Fasting plasma glucose
was measured by the glucose-peroxidase colorimetric enzymatic method (Biodiagnostica, Germany). Serum creatinine was measured by the Jaffe method, serum total
cholesterol and triglycerides were measured by enzymaticcolorimetric methods (Merck Diagnostica, Darmstadt, Germany; Boehringer Mannheim, Buenos Aires, Argentina)
and HDL cholesterol by the homogeneous direct method
(autoanalyser, ADVIA 1650, Germany). LDL cholesterol
was calculated using the Friedewald formula.

C. K. Kramer et al.

Bacteriuria and urinary albumin excretion

already been described in patients with diabetes [16,17].

In a prospective study, Hernandez et al. studied 46 diabetic patients with bacteriuria and found no differences
in 24-h urinary albumin excretion from urine samples before and after eradication (11.7 versus 7.1 g/min, P =
0.14) [16]. However, the estimated power to find a difference of 10 g/min in albuminuria measurements was
68%. On the other hand, in the present study the power
of the observed non-significant difference between UAC
measurements in samples with and without bacteriuria was
80%. In a prospective study, 172 type 1 DM patients had
24-h urinary albumin excretion measured six times during
18 months. During the follow-up in the 20 patients who had
bacteriuria or urinary tract infection, the urinary albumin
measurements did not change [18]. However, as in the study
of Hernandez et al. [16], the small sample of patients with
bacteriuria does not allow an accurate conclusion.
As far as we know, the evaluation of bacteriuria interference in albuminuria measurements in spot urine samples
has not been studied in diabetic patients. This information is critical for routine practice since the use of spot
urine, due to its easy collection, has been recommended as
the screening method for the diagnosis of DN [1,7,10]. It
was demonstrated that in a random urine spot sample using UAC for DN screening is as accurate as and cheaper

than the albumin-to-creatinine ratio [11]. According to the

data from the present study, the costs for diagnosis of DN
can be further reduced without performing a concomitant
urine culture. Other reasons for not routinely performing
urine cultures in diabetic patients is that bacteriuria is often
found and asymptomatic bacteriuria occurs in up to 17.5%
of diabetic women [19]. Furthermore, treatment of patients
with asymptomatic bacteriuria is not recommended [20].
Even in patients with increased serum creatinine, the presence of bacteriuria was not associated with the decline of
renal function reinforcing the benign role of asymptomatic
bacteriuria [21]. Interestingly, in the present study, patients
with bacteriuria had higher serum creatinine values than
patients without bacteriuria.
A possible limitation of the present study was the measurement of urine albumin concentration instead of the
albumin-to-creatinine ratio. Theoretically, isolated albumin
concentration measurements could be influenced by urine
dilution. Other authors observed that the measurement of
the albumin-to-creatinine ratio was more accurate than the
albumin concentration for the diagnosis of microalbuminuria when using sex- and age-specific discriminator values
[22]. However, there is a strong correlation between the
urinary albumin concentration and the urinary albuminto-creatinine ratio as we [11] and others [22] had already

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Fig. 1. Urinary albumin concentration in the first and second random spot urine samples in case and control groups.

Acknowledgements. This study was partially supported by PRONEX,

CNPq, FIPE-HCPA and CAPES.

8.

9.
10.

11.

12.
13.

14.

Conflict of interest statement. None declared.

15.

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Received for publication: 13.5.08

Accepted in revised form: 17.10.08

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demonstrated, but these data were obtained in the absence

of bacteriuria [11]. In the present study, the urine specific gravity was not different between cases and controls
(Table 1), and therefore, the absence of creatinine measurements in urine samples probably did not influence our
results. Another aspect is the preponderance of the female
sex, both in cases and controls. This finding might be explained by increased urine culture requests for women due
to a known increased prevalence of urinary infection in diabetic women [18]. However, this feature did not influence
the analytical evaluation of urine samples.
In conclusion, the presence of bacteriuria does not interfere significantly in the interpretation of urinary albumin
measurements, and a urine culture might not be necessary
at the time of DN diagnosis.

C. K. Kramer et al.