51 Stutzin, Godofredo, El Arrayán,
2.4.3 ANALISIS DEL ARTÍCULO 43 DE LA LEY DE GESTION AMBIENTAL:
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CHAPTER FIVE RESULTS
BACKGROUND DESCRIPTION OF PARTICIPANTS
SOCIAL DEMOGRAPHIC CHARACTERISTICS OF PARTICIPANTS
One hundred and forty-five participants were recruited for the study. Forty participants were controls, 42 had diabetic without nephropathy and 63 participants had diabetic nephropathy. The average age between the groups of participants: 52.9±6.4 years, 57.4±8.2 and 57.7±7.5 years for control, DM and Diabetic with Nephropathy group (p=0.004). The diabetic group had more males, 23 (54.8%) when compared to other groups.
The majority of participants were females except amongst the diabetic group who had more males (p=0.019). There was no difference in marital status between the groups of participants (p=0.375). It was also noticed that the participants with diabetes nephropathy had poorer educational status when compared to other groups (p<0.001). Table 1.
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Table 1: Socio-demographic Variables of Participants DN
N=63
DM N=42
Controls N=40
p
Age (Mean, SD) 57.7 (7.5) 57.4 (8.2) 52.9 (6.4) 0.004
Sex (N, %)
Male 20 (31.8) 23 (54.8) 11 (27.5) 0.019
Female 43 (68.2) 19 (45.2) 29 (72.5)
Marital status (N, %)
Married 53 (84.6) 36 (86.1) 38 (95.0) 0.375
not married 10 (15.4) 6 (14.3) 2 (5.0)
Education (N, %)
None 24 (38.1) 4 (9.5) - <0.001
Primary 17 (27.0) 6 (14.2) 4 (10.3)
Secondary 13 (20.6) 14 (33.3) 15 (38.5)
Tertiary 9 (14.3) 18 (42.9) 20 (51.3)
DN: diabetic nephropathy. DM: Diabetes only. P: p-value.
*Statistically Significant.
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CLINICAL CHARACTERISTICS IN THE DIABETIC GROUPS, DIABETIC NEPHROPATHY GROUPS AND CONTROL GROUP
Table 2 shows clinical characteristics in the three different groups. While participants with diabetes had similar median duration of the disease, 35 (55.6%) of those with diabetes nephropathy had co-existing hypertension as opposed to 20 (47.2%) of the diabetic group (p-value<0.001). There was no significant difference in the duration of hypertension between these groups (p-value=0.343)
There was no difference in BMI and waist hip ratio of each groups. The mean BMI among diabetic nephropathy group and diabetic group were 27.9±4.7 kg/m2 and 26.9±5.6 kg/m2 respectively, for controls was 25.2±2.9 kg/m2. The mean waist hip ratio among diabetic nephropathy group and diabetic mellitus group were 1.0±0.1 and 1.0±0.2 respectively, for controls 0.9±0.1 (p-value = 0.067 and 0.180 respectively)
Systolic blood pressure values were higher among the diabetic nephropathy group 132.6±16.6 mmHg and diabetic group 122.7 ±15.2 mmHg than that of the controls 109.9±11.3 mmHg (p-value <0.001). Diastolic blood pressure were also higher the diabetic nephropathy group 80.7 ±9.9 mmHg and diabetic group 79.6 ±10.4 mmHg than that of the controls 73.3±8.3 mmHg (p-value=0.001).
50 Table 2: Clinical Characteristics of Participants
DN N=63
DM N=42
Controls N=40
p
DM Duration in weeks (Median, Range) 96 (12 – 444) 72 (2 – 240) - 0.255
Hypertension (N, %) 35 (55.6) 20 (47.2) - <0.001
BMI in kg/m2 (Mean, SD) 27.9 (4.7) 26.9 (5.6) 25.2 (2.9) 0.079 Waist hip ratio (Mean, SD) 1.0 (0.1) 1.0 (0.2) 0.9 (0.1) 0.199 HTN Duration in weeks (Median, Range) 60 (2 – 159) 42 (1 – 210) - 0.343 Heart Rate (Mean, SD) 78.8 (11.6) 77.4 (13.4) 77.3 (8.8) 0.739
1Systolic BP (Mean, SD) 132.6 (16.6) 122.7 (15.2) 109.9 (11.3) <0.001
1Diastolic BP (Mean, SD) 80.7 (9.9) 79.6 (10.4) 73.3 (8.3) 0.001 DN: diabetic nephropathy. DM: Diabetes only. P: p-value.
*Statistically Significant.
1Post-Hoc Bonferroni showed no significant difference between DM & DN.
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LABORATORY PARAMETERS OF PARTICIPANTS
The mean creatinine for the diabetic nephropathy group, diabetic group and controls were 1.8±0.7mg/dl, 1.3±1.1mg/dl and 0.5±0.3mg/dl respectively (p<0.001). Investigation results done for participants showed that there was significant difference in creatinine level – participants with Diabetic nephropathy group had the highest mean creatinine levels.
The median eGFR among the diabetic nephropathy group, diabetic group and controls were 46.2 (32.7 – 54.6) ml/min/1.732,84.1 (69.3 – 113.7) ml/min/1.732, 135.5 (118.8 – 179.4) ml/min/1.732 respectively (p <0.001). The mean HBA1c among the diabetic nephropathy group, diabetic group and controls 6.9±1.2%, 7.1 ±1.7% and 5.1±0.9% respectively (p < 0.001). There were significant differences between groups in serum lipid parameters apart from HDL &
triglyceride. The mean cholesterol level among the diabetic nephropathy group, diabetic group and controls were 171.9±38.3 mg/dl, 168.1±35.0 mg/dl, 140.6 ±14.1 mg/dl respectively (p=0.001). The mean LDL level among the diabetic nephropathy group, diabetic group and controls were 106.4±41.0 mg/dl, 101.5±43.5 mg/dl, 76.9±22.3 mg/dl respectively (p=0.001). See Table 3.
52 Table 3: Laboratory Parameters of Participants
DN N=63
DM N=42
Controls N=40
P
2Creatinine (mg/dl) (Mean, SD) 1.8 (0.7) 1.3 (1.1) 0.5 (0.3) <0.001*
1eGFR (mls/min/1.73m2) (Med, IQR) 46 (33-55) 84 (69-114) 136 (120-180) <0.001*
2Hba1c (%) (Mean, SD) 6.9 (1.2) 7.1 (1.7) 5.1 (0.9) <0.001*
Lipid Profile (mg/dl)
HDL (Mean, SD) 43.9 (13.1) 40.3 (13.3) 43.4 (14.1) 0.431
2Cholesterol (Mean, SD) 171.9 (38.3) 168.1 (35.0) 140.6 (41.1) <0.001*
Triglycerides (Mean, SD) 116.6 (27.5) 109.2 (35.0) 104.5 (31.6) 0.160
2LDL (Mean, SD) 106.4 (41.0) 101.5(43.5) 76.9 (22.3) 0.001*
DN: diabetic nephropathy. DM: Diabetes only. P: p-value.
*Statistically Significant.
1Post-Hoc Bonferroni shows significant difference between all groups.
2Post-Hoc Bonferroni showed no significant difference between DM & CKD.
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Figure 7 below shows prevalence of albuminuria in the diabetic nephropathy, diabetic and control groups. None of the participants in the control group & diabetic group were noted to have albuminuria. 31 (50.0%) and 6 (9.7%) of those with diabetic nephropathy had micro-albuminuria and macro-micro-albuminuria respectively.
Figure 7: Frequency of Occurrence of Albuminuria in Participants.
0 20 40 60 80 100 120
Normal DM DN
Percentages
Frequency of Occurrence of Albuminuria
Normo-albuminuria Micro-albuminuria Macro-albuminuria
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DISTRIBUTION OF ULTRASONOGRAPHIC PARAMETERS AMONG THE THREE GROUPS
The findings on renal ultrasound are shown in Table 4. The RI in the left inter-lobar artery for diabetic nephropathy group, diabetic group and controls were 0.70±0.08, 0.57±0.06 and 0.54±0.04 respectively (p=0.001). The RI in the right inter-lobar artery 0.70±0.07, 0.59±0.06 and 0.54±0.04 respectively (p <0.001). The mean RI for the diabetic nephropathy group, diabetic group and controls 0.70±0.06, 0.61±0.04 and 0.54±0.04 respectively (p <0.001).
Participants in the Diabetic group and Diabetic nephropathy group had significantly higher average resistive index when compared to the controls. Other ultrasound renal parameters were comparable apart from antero-posterior diameter where participants in the Diabetic group had the highest diameters on the right but controls had the highest on the left. See Table 5.
55 Table 4: Mean (SD) Resistive Index of Participants
DN N=63
DM N=42
Controls N=40
P
1Left Inter-lobar artery RI 0.70 (0.08) 0.57 (0.06) 0.54 (0.04) <0.001*
Right Inter-lobar artery RI 0.70 (0.07) 0.59 (0.06) 0.54 (0.04) <0.001*
Average RI 0.70 (0.06) 0.61 (0.04) 0.54 (0.04) <0.001*
DN: diabetic nephropathy. DM: Diabetes only. P: p-value*Statistically Significant.
1post-hoc Bonferroni shows no difference between DM and Controls
Table 5: Renal Parameters of Participants DN N=63
DM N=42
Controls N=40
P
Right longitudinal diameter (cm) 10.6 (0.8) 10.2 (0.4) 10.8 (1.8) 0.489 Left longitudinal diameter (cm) 10.9 (0.9) 11.0 (0.7) 10.7 (0.8) 0.247 Right AP diameter (cm) 4.3 (0.7) 4.2 (0.8) 3.8 (0.6) 0.001*
Left AP Diameter (cm) 4.9 (0.7) 4.9 (1.0) 5.3 (0.7) 0.024*
Right transverse diameter (cm) 5.2 (0.6) 5.3 (1.2) 5.5 (1.6) 0.349 Left transverse diameter (cm) 5.2 (0.5) 5.3 (0.6) 5.1 (0.8) 0.451 Right renal volume (cm3) 124.0 (34.8) 115.6 (23.2) 109.6 (21.5) 0.042 Left renal volume (cm3) 142.9 (31.5) 129.8 (40.3) 142.4 (25.9) 0.207 Right cortical thickness (cm) 1.3 (0.2) 1.4 (0.3) 1.3 (0.2) 0.106 Left cortical thickness (cm) 1.5 (0.1) 1.5 (0.2) 1.5 (0.2) 0.198
DN: diabetic nephropathy. DM: Diabetes only. P: p-value.
*Statistically Significant.
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PROPORTION OF PARTICIPANTS IN DIFFERENT RESISTIVE INDEX CATEGORIES
Resistive index was grouped into categories, none of the control had RI above 0.7. Proportion of participants among the DM and DN group with elevated RI was 1 (2.4%) and 35 (55.6%). See figure 8.
P-value: 0.0001
Figure 8: Proportion of Participants in different Resistive Index Categories
0 20 40 60 80 100 120
DN DM Control
Percentage
RI
<0.7 >0.7
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RELATIONSHIP BETWEEN RESISTIVE INDEX AND RENAL FUNCTION OF PATIENTS WITH DIABETIC NEPHROPATHY
Scatter plot in Figure 2 below shows a positive correlation between level of micro-albuminuria and RI.
Figure 9: Scatterplot showing Relationship between RI and MA in DN Participants
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CORRELATION BETWEEN MEASURES OF RENAL FUNCTIONS AND RESISTIVE INDEX
The correlation between resistive index and micro-albuminuria and eGFR are shown in Table 7 and Table 8 below. Spearman rank rho results showed moderate correlation between MA and RI in the participants with DN but lost correlation when stratified according to groups. There was a strong negative correlation between eGFR and resistive index in all participants with moderate and strong correlation in the diabetics and DN participants respectively.
VARIABLE ASSOCIATED WITH INCREASED RESISTIVE INDEX AMONG PATIENTS WITH DIABETIC NEPHROPATHY
Table 9 below shows variables that have significant correlation with average RI in participants with diabetes. Systolic blood pressure and HBA1c levels showed strong positive correlation with average RI, while eGFR showed strong negative correlation in all participants (rho: 0.51, 0.54, -0.81 respectively). BMI, age, cholesterol levels, triglyceride levels, LDL levels and diastolic blood pressure showed moderate positive correlation with average RI in all participants with rho values ranging from 0.23 – 0.28. Total cholesterol was the only variable that showed significant correlation (rho: 0.325) with average RI among the diabetic nephropathy group.
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Table 7: Correlation between Micro-albuminuria and Resistive Index
Total Controls DM DN
Left Inter-lobar Artery 0.28* 0.04 0.01 -0.09
Right Inter-lobar Artery 0.34* 0.04 -0.12 0.03
Average RI 0.35* 0.10 0.04 0.03
*Statistical significant association.
Table 8: Correlation between eGFR and Resistive Index
Total Controls DM DN
Left inter-lobar artery -0.78* -0.09 -0.47* -0.71*
Right inter-lobar artery -0.77* -0.20 -0.29* -0.64*
Average RI -0.81* -0.16 -0.39* -0.65*
*p-value <0.01
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Table 9: Correlation between Selected Variables and RI
All DM Patients DM DN
Diabetes Duration 0.155 0.280 0.137
Hypertension Duration 0.013 -0.048 -0.088
BMI 0.250** 0.028 0.221
WHR 0.062 -0.058 0.063
PCV -0.050 -0.179 -0.248
Age 0.229** 0.219 0.145
Hba1c 0.538** 0.089 -0.053
HDL -0.004 0.022 -0.075
Cholesterol 0.235** -0.006 0.325*
Triglycerides 0.246** 0.063 0.243
LDL 0.270** -0.067 -0.133
Systolic BP 0.512** 0.095 0.163
Diastolic BP 0.275** 0.039 0.166
Pulse 0.109 0.048 -0.201
eGFR -0.812** 0.018 -0.223
*p-value <0.05. **p-value <0.01
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Table 10 below shows that there were no correlation between RI and renal parameters among the participants with diabetes.
Table 10: Spearman Correlation between Renal Parameters and RI
Rho p-value
Right longitudinal diameter -0.024 0.819
Left longitudinal diameter -0.117 0.260
Right AP diameter 0.143 0.171
Left AP Diameter 0.090 0.388
Right transverse diameter 0.104 0.318
Left transverse diameter 0.003 0.976
Right renal volume -0.032 0.761
Left renal volume 0.026 0.805
Right cortical thickness 0.137 0.190
Left cortical thickness -0.010 0.922
63 INDEPENDENT CORRELATIONS OF RI
A multiple linear regression was modelled to determine variables that were independently linked with resistive index. Variables that showed correlations with RI were added to the model with the eGFR excluded due to multi-collinearity with participant group. Results showed that when all interested variables were considered together, they significantly predicted resistive index (R2: 0.403, p-value <0.001). The presence of diabetic nephropathy determined by eGFR showed independent correlation with RI (beta=0.54, p-value<0.001) while urinary albumin-creatinine ratio had an independent inverse correlation with RI (beta=-0.06, p-value<0.001).
Table 10 shows the regression result.
64 Table 11: Independent Correlations of RI
BETA SE P-VAL
Age (Years) -0.01 0.001 0.933
BMI 0.06 0.001 0.563
HBA1c 0.06 0.004 0.559
Cholesterol -0.01 0.01 0.948
LDL -0.08 0.01 0.427
Triglyceride 0.20 0.00 0.071
urinary Alb/Cr -0.06 0.01 0.000*
Group 0.54 0.02 0.000*
R2: 0.403, F: 7.1, p-value: 0.000.
*Statistically Significant.
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Figures 10 shows the outcomes of the ROC analysis for the resistivity index associated with diabetes nephropathy. RI attained showed good diagnostic accuracy with the area under the receiver operating curve (AUC) at 0.99 (95% CI: 0.97 – 1.00). Using a cut off of 0.7, sensitivity and specificity of 66% and 100% respectively, PPV and NPV are 100% and 81.8% respectively.
See Figure 10 below
Figure 10 showing ROC curve.
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CHAPTER 5