Patient and control characteristics
The study groups consisted of patients with selected urological diseases of the urinary tract such as: benign prostatic hyperplasia (BPH), urethral stricture (US), urinary tract infection (UTI) and urolithiasis, and included men and women. The groups of patients with BPH and US were male only, while the groups of patients with UTI and urolithiasis were formed of both women and men. Therefore, two control groups: C1 (consisting only of men) and C2 (consisting of both men and women) were created. No statistically significant differences in characteristic features were observed between the patient groups and the control groups. The age and sex of patients with the selected urinary diseases and the control group were not different (p >0.05). The demographic and clinical characteristics of the examined groups are shown in Table 1.
Table 1. Demographic and clinical data of patients and the control groups.
Population characteristic
|
Patients
|
Control groups
|
N
|
44
|
32 (C2)
|
Age, y, (range)
|
62 (21 - 83)
|
63 (40 - 78)
|
Man (%)
|
36 (82)
|
27(84) (C1)
|
Age, y, (range)
|
63 (21 - 83)
|
64 (45 - 82)
|
Women (%)
|
8 (18)
|
5 (16)
|
Age, y, (range)
|
57 (28 - 73)
|
59 (42 - 71)
|
BPH
|
|
|
Man (%)
|
13 (100)
|
|
Age, y, (range)
|
69 (55 - 83)
|
|
US
|
|
|
Man (%)
|
7 (100)
|
|
Age, y, (range)
|
53 (21 - 67)
|
|
UTI
|
|
|
N(%)
|
17 (37)
|
|
Man (%)
|
12 ( 27)
|
|
Age, y, (range)
|
62 (33 - 73)
|
|
Women (%)
|
5 (11)
|
|
Age, y, (range)
|
64 (50 - 73)
|
|
Urolithiasisis
|
|
|
N(%)
|
7 (16)
|
|
Man (%)
|
4 (9)
|
|
Age, y, (range)
|
60 (48 - 67)
|
|
Women (%)
|
3 (7)
|
|
Age, y, (range)
|
47 (25 - 73)
|
|
Abbreviation: BPH - benign prostatic hyperplasia; US - urethral stricture; UIT- urinary
tract infection; C1 - control group (man); C2 - control group (man and woman); N - number
of patients; y - years
The analysis of the results was carried out in two parts. The first analysis of the UPs results concerned patients with BPH, US and the C1 control group, composed of men. The second analysis of the UPs results concerned patients with UTI, urolithiasis and C2, which were both male and female.
UPIIIa and UPII in the urine and plasma of patients with BPH, US and control group C1
The mean concentrations and standard deviation of UPIIIa and UPII in the urine and plasma of patients with BHP, US and control group (C1) are presented with statistical analysis in Table 2.
Table 2. Results for UPIIIa and UPII in patients with BPH, US and C1.
UPs
|
BHP
mean±SD
|
US
mean±SD
|
C1
mean±SD
|
p*
|
UPIIIa (urine)
[ng/mg cr.]
|
2.22±1.48
|
1.39±0.63
|
0.98±0.56
|
<0.001
|
UPIIIa (plasma)
[ng/mL]
|
2.07±0.35
|
1.94±0.43
|
0.59±0.33
|
<0.001
|
UPII (urine)
[ng/mg cr.]
|
0.34 ±0.25
|
0.23± 0.20
|
0.08± 0.04
|
<0.001
|
UPII (plasma)
[ng/mL]
|
3.41±0.76
|
3.21±1.73
|
2.79±0.65
|
0.019
|
p*-values were calculated using one-way ANOVA analysis of variance
Abbreviation: BPH - benign prostatic hyperplasia; US - urethral stricture; SD – standard
deviation; C1 - control group (man)
Statistically significant differences were found analyzing groups of patients with BPH, US and C1 group for UPIIIa and UPII in both urine and plasma (one-way ANOVA test), (Table 2).
The mean urinary and plasma concentration of UPIIIa in BPH patients was 2.3-fold and 3.5-fold higher than in the control group (C1), respectively. UPIIIa in both urine and plasma of BPH patients showed a statistically significant difference compared to the control group (p <0.001). The mean urinary and plasma concentration of UPII in BPH patients was 4.3-fold and 1.2-fold higher than in the control group, respectively. UPII in the urine of BPH patients was statistically significantly higher than in the control group (p<0.001), but in the plasma UPII did not differ significantly relative to the C1.
The mean urinary and plasma concentration of UPIIIa in US patients was 1.4-fold and 3.2-fold higher than in the control group (C1), respectively. In patients with US mean values of plasma UPIIIa were higher compared to the concentrations of these uroplakin obtained in the group C1, (p<0.001), but there was no significant difference between the concentration of UPIIIa compared to C1 in urine. The mean urinary and plasma concentration of UPII in US patients was 2.9-fold and 1.4-fold higher than in the control group, respectively. There was no significant difference between the values of UPII concentration in patients with US compared to C1 in urine and plasma.
UPIIIa and UPII in the urine and plasma of patients with UTI, urolithiasis and control group C2
The mean concentrations and standard deviation of UPIIIa and UPII in the urine and plasma of patients with UTI, urolithiasis and control group (C2) are presented with statistical analysis in Table 3.
Table 3. Results for UPIIIa and UPII in patients with UTI, urolithiasis and control group C2.
UPs
|
UTI
mean±SD
|
Urolithiasisis
mean±SD
|
C2
mean±SD
|
p*
|
UPIIIa (urine)
[ng/mg cr.]
|
1.62±0.75
|
1.46±0.47
|
0.99±0.52
|
0.002
|
UPIIIa (plasma)
[ng/mL]
|
1.86±0.49
|
1.78±0.28
|
0.59±0.31
|
<0.001
|
UPII (urine)
[ng/mg cr.]
|
0.25±0.14
|
0.19±0.11
|
0.08±0.04
|
<0.001
|
UPII (plasma)
[ng/mL]
|
3.19±1.01
|
3.39±0.57
|
2.72±0.68
|
NS
|
p* - values were calculated using one-way ANOVA analysis of variance
Abbreviation: UIT - urinary tract infection; SD - standard deviation; NS - not statistically
significant; C2 - control group (man and woman)
Statistically significant differences were found analyzing groups of patients with UTI, urolithiasis and C2 group for UPIIIa in urine and plasma and UPII in urine (Table 3).
The mean urinary and plasma concentration of UPIIIa in UTI patients was 1.6-fold and 3.1-fold higher than in the control group, respectively. UPIIIa in both urine and plasma of UIT patients showed a statistically significant difference compared to the control group (C2), (p <0.001). The mean urinary and plasma concentration of UPII in UTI patients was 3.2-fold and 1.2-fold higher than in the control group (C2), respectively. UPII in the urine of UTI patients was statistically significantly higher than in the control group (p<0.001), but the plasma UPII did not differ significantly from the value obtained in C2.
The mean urinary and plasma concentration of UPIIIa in urolithiasis patients was 1.5-fold and 2.9-fold higher than in the control group, respectively. The mean urinary and plasma concentration of UPII in urolithiasis patients was 2.4-fold and 1.2-fold higher than in the control group (C2), respectively. In the group of patients with urolithiasis, both UPIIIa and UPII in urine and plasma showed no statistically significant differences compared to the control group C2.
Visualizations of the obtained results of UPIIIa and UPII in urine and plasma of patients with selected benign urological diseases are presented in Figure 1.
Abbreviation: BPH - benign prostatic hyperplasia; US - urethral stricture; UTI - urinary tract infection; Urolith. – urolithiasis; C1 - control group (man); C2 - control group (man and woman)
There were no statistically significant differences between the values of UPIIIa and UPII concentrations in the urine and plasma of patients with selected benign urological diseases in relation to each other.
Mutual correlations between UPIIIa and UPII
Mutual positive correlations between UPIIIa (urine) and UPIIIa (plasma) in BPH and UTI were demonstrated. Such correlations were not found in the case of UPII. Urine UPIIIa correlated with urine UPII in patient groups with BPH and UTI (Table 4).
Table 4. Correlations between UPIIIa and UPII in patients with selected urological diseases.
Correlations between UPIIIa and UPII
|
r
|
p*
|
BPH - UPIIIa ( plasma ) vs UPIIIa ( urine)
|
0.59
|
0.03
|
UTI - UPIIIa (plasma) vs UPIIIa (urine)
|
0.61
|
0.01
|
BPH - UPIIIa ( urine) vs UPII ( urine)
|
0.64
|
0.01
|
UTI - UPIIIa (urine) vs UPII (urine)
|
0.50
|
0.04
|
p* - significant difference (Pearson test); r - Pearson correlation coefficient;
Abbreviation: BPH - benign prosaic hyperplasia; UTI - urinary tract infection
ROC curves analysis for UPIIIa and UPII in selected benign urological diseases
The diagnostic value of the examined UPIIIa and UPII in both biological fluids (plasma and urine) were evaluated. Figure 2 shows the receiver operating curves (ROC) for UPIIIa and UPII, which obtained the best diagnostic values. ROC curve analysis of UPIIIa (BPH-plasma), UPIIIa (UTI-plasma), UPIIIa (BPH-urine), UPIIIa (UTI-urine), UPII (BPH-urine) and UPII (UTI-urine) conducted for examined UPs showed an area under the curve (AUC) of 99% [95% confidence interval (CI) (99–100%), p<0.001), sensitivity 100%, specificity 99%], 99% [95% CI (99–100%, p<0.001), sensitivity 99%, specificity 97%], 89% [95% CI (79–99%, p<0.001), sensitivity 92%, specificity 88%], 79% [95% CI (65–93%, p<0.001), sensitivity 82%, specificity 75%], 74% [95% CI (58-89% p=0.003), sensitivity 99%, specificity 72%], 63% [95% CI (45-79% p=0.162), sensitivity 84%, specificity 51%], respectively (Fig.2).
The cut-off values for UPIIIa (BPH-plasma), UPIIIa (UTI-plasma), UPIIIa (BPH-urine), UPIIIa (UTI-urine), UPII (BPH-urine) and UPII (UTI-urine) were 1.46 ng/mL, 1.29ng/mL, 1.26 ng/mg creatinine, 1.17ng/mg creatinine, 0.13ng/mg creatinine, 0.11 ng/mg creatinine, respectively (Fig.2).