|Year : 2018 | Volume
| Issue : 2 | Page : 544-549
Duplex ultrasound in the evaluation of early renal hemodynamics alteration in type I diabetics
Zeinab A Ali, Waleed A Mousa, Sherif M Shalaby
Department of Radiodiagnosis, Faculty of Medicine, Menoufia University, Shebeen El-Kom, Egypt
|Date of Submission||13-Nov-2017|
|Date of Acceptance||24-Dec-2017|
|Date of Web Publication||27-Aug-2018|
Sherif M Shalaby
Department of Radiodiagnosis, National Institute of Diabetes and Endocrinology, Cairo 2002
Source of Support: None, Conflict of Interest: None
Diabetic nephropathy affects ~40% of patients with type I diabetes mellitus. Once fully developed, it carries a poor prognosis, where relative mortality is almost 40–100 times that of nondiabetics. Evaluation of vascular resistivity at multiple points of renal parenchyma may suggest structural or functional changes within the kidneys and can provide useful diagnostic and prognostic information.
The aim of this study was to detect possible changes of renal blood flow and vascular indices in children and adolescents with type I diabetes mellitus, using duplex ultrasonography, and to correlate these changes with clinical and laboratory parameters results.
Participants and methods
Twenty-five type I diabetic child and adolescent and 25 nondiabetic child and adolescent (control) were included in the study. After ethics committee approval and obtaining patient consent, the study included 13 females and 12 males in each group, with mean age of 10.3 years ± 4.31 SD in both groups. All patients are subjected to: full history, fasting blood sugar analysis, creatinine level, HBA1C, microalbuminuria, and albumin/creatinine ratio. Renal Doppler ultrasound for each case was done.
Statistically significant differences were detected between diabetic and control cases regarding resistive index of main renal, segmental, and interlobar arteries. The results were compared against serum creatinine, albumin/creatinine ratio, and glycated hemoglobin.
Our study showed some differences in the resistive index of main renal, segmental, and interlobar arteries between children with type I diabetes and age-matched healthy controls. Moreover, there is a significant positive correlation between the resistive index of these arteries and duration of diabetes, albumin/creatinine ratio (mg/mmol), and serum creatinine level (mg/dl).
Keywords: diabetes mellitus, diabetic nephropathy, microalbuminuria, renal biomarkers, renal Doppler, renal hemodynamics, resistive index
|How to cite this article:|
Ali ZA, Mousa WA, Shalaby SM. Duplex ultrasound in the evaluation of early renal hemodynamics alteration in type I diabetics. Menoufia Med J 2018;31:544-9
|How to cite this URL:|
Ali ZA, Mousa WA, Shalaby SM. Duplex ultrasound in the evaluation of early renal hemodynamics alteration in type I diabetics. Menoufia Med J [serial online] 2018 [cited 2018 Nov 21];31:544-9. Available from: http://www.mmj.eg.net/text.asp?2018/31/2/544/239772
| Introduction|| |
Diabetic nephropathy affects ~40% of patients with type I diabetes mellitus. Once fully developed, this complication carries a poor prognosis where relative mortality is almost 40–100 times that of nondiabetics .
Therefore, it is considered one of the most common and most serious complications in type I diabetes. Glomerular hyperfiltration is the first feature of renal involvement and can be observed soon after the inception of diabetes, accompanied by a loss of renal functional reserve. Microalbuminuria coincides with the morphological changes such as thickening of the glomerular basement membrane and mesangial expansion .
Clinically evident diabetes-related microvascular complications are extremely rare in childhood and adolescence. Nonetheless, early functional and structural abnormalities may be present a few years after the onset of the disease .
Ultrasonography (US) and color Doppler are used in the initial evaluation, as both are widely available, easy to perform, inexpensive, and have no undesired adverse effects . Evaluation of vascular resistivity at different sites of the renal parenchyma may suggest functional or structural changes within the kidneys and could provide useful diagnostic and prognostic information .
Therefore, correlating the ultrasound and color duplex findings with clinical and laboratory parameters in children and adolescents with type I diabetes mellitus is a way of predicting alterations in renal hemodynamics and predicting the course of diabetic nephropathy .
The aim of this work is to detect possible changes in renal blood flow and vascular indices by duplex ultrasonography, and correlation of these changes with clinical and laboratory parameters results in children and adolescents with type I diabetes mellitus.
| Participants and Methods|| |
Consequently, upon Ethical Committee approval, the prospective case–control randomized study started by including 25 type I diabetic child and adolescent and 25 normal nondiabetic child and adolescent (control group) who are referred to 'National Institute of Diabetes and Endocrinology', Cairo, for routine outpatient checkup and assessment. The study included 13 females and 12 males in each group, with mean age of 10.3 years ± 4.31 SD at both groups (ranged between 3 and 18 years). The study took about a year, starting from June 2016 to June 2017.
Inclusion criteria were specifically type I diabetic patients with no clinical symptoms or laboratory signs for nephropathy as a diabetic group and normal age-matched and sex-matched healthy children with no medical disorders as a control group; all individuals were subjected to routine checkup.
Exclusion criteria were cases with clinical and laboratory evident diabetic nephropathy, in addition to cases of type II diabetes mellitus.
Each case, after having written consent, explained the full procedure, nature of the study and absence of invasive or radiation hazards exposure with approval to use the cases' data for medical research, was subjected to the following: full history, including age, sex, and history of any associated medical disorders or drug intake and type of diabetes, duration of diabetes, and glycemic status (for diabetic group). Fasting blood sugar analysis results are obtained to differentiate between diabetic and control cases. Creatinine level, HBA1C, microalbuminuria, and albumin creatinine ratio were done for each group (diabetic and control group). Renal Doppler, color and power Doppler, ultrasound was done afterward for each case (diabetic and control groups).
The patients were examined in a fasting state, with a low-frequency transducer operating at 2.0–3.5 MHz. The machines used in duplex ultrasound were Toshiba Xario TM200 (Toshiba Medical Systems Corporation, Tokyo, Japan), Philips iU22 xMatrix DS Ultrasound (Philips Medical System Corporation, Eindhoven, the Netherlands). Laboratory tests mentioned were done using 'ARCHITECT c 8000' clinical chemistry analyzer (Abbott, Abbott Park, Illinois, USA).
Angle-corrected velocity measurements were taken at five points along the course of the main renal arteries (MRA), with the mean value of these measurements calculated. After tracing and assessing the MRA of each kidney, the segmental artery (SA), and interlobar artery (ILA) were assessed with peak systolic velocity (PSV), end diastolic velocity (EDV), and eventually resistive index (RI) measured for each one along five points for each artery, with mean value calculated as well. The same technique for tracing and optimizing the parameters was applied to these arteries.
Data were analyzed using SPSS win statistical package, version 21 (SPSS Inc., Chicago, Illinois, USA). Numerical data were expressed as mean and SD or median and range as appropriate. Qualitative data were expressed as frequency and percentage. χ2-Test was used to examine the relation between qualitative variables. For quantitative data, comparison between two groups was done using Mann–Whitney test as appropriate. A P value of less than 0.05 was considered significant.
| Results|| |
The mean RI of MRA of was 0.57 ± 0.02 SD in the control group versus 0.59 ± 0.3 SD in the diabetic group. The mean RI of SA was 0.62 ± 0.01 SD in the control group versus 0.66 ± 0.02 SD in the diabetic group. The mean RI of ILA was 0.64 ± 0.01 SD in the control group versus 0.68 ± 0.02 SD in the diabetic group.
The RI of MRA (P = 0.001), RI of SA (P < 0.001), and RI of ILAs (P < 0.001) were significantly higher in the diabetic group [Figure 1]a, [Figure 1]b, [Figure 1]c, [Figure 1]d, [Figure 1]e, [Figure 1]f.
|Figure 1: (a–f) Case no. 1 and 2. Ul traso und scan study with color Doppler, showing: (a) resistive index (RI) of main renal artery (MRA) in a 13 year-old male patient with type I DM (6 years ago), (b) RI of segmental artery (SA) in a13 year-old male patient with type I DM (6 years ago), (c) RI of interlobar artery (ILA) in a 13 year-old male patient with type I DM (6 years ago), (d) RI of MRA in a 13 year-old control male patient within normal ranges according to reference values, (e) RI of SA in a 13 year-old control male patient within normal ranges according to reference values, and (f) RI of ILA in a 13 year-old control male patient within normal ranges according to reference values.|
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The mean microalbuminuria (mg/day) was zero in the control group versus 10.92 ± 8.47 SD in the diabetic group.
The mean serum creatinine level was 0.68 mg/dl ± 0.2 SD in the control group versus 0.7 mg/dl ± 0.2 SD in the diabetic group. There is no significant difference in serum creatinine level (P = 0.73) between the two groups.
Albumin/creatinine ratio (mg/mmol) (P < 0.001) was significantly higher in the diabetic group in comparison with the control group [Table 1].
|Table 1 Comparison of resistive index and laboratory findings, between control and diabetic groups|
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The serum creatinine level shows significant correlation with age in both the control and diabetic groups (r = 0.873); it is same value in the diabetic and control groups because mean age is the same in both the groups [Figure 2]a, [Figure 2]b, [Figure 2]c, [Figure 2]d, [Figure 2]e, [Figure 2]f.
|Figure 2: (a–f) Case no. 2 and 3. Ultrasound scan study with color Doppler, showing: (a) resistive index (RI) of main renal artery (MRA) in a 4 year-old female patient with type I DM (2 years duration), (b) RI of segmental artery (SA) in a 4 year-old female patient with type I DM (2 years duration), (c) RI of interlobar artery (ILA) in a 4 year-old female patient with type I DM (2 years duration), (d) Resistive index (RI) of MRA in a 9 year-old female patient with type I DM (7 years duration), (e) RI of SA in a 9 year-old female patient with type I DM (7 years duration), and (f) RI of ILA in a 9 year-old female patient with type I DM (7 years duration).|
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There is no significant difference in the mean RI found between right and left kidney in both the groups [Table 2].
|Table 2 The mean resistive index of main renal artery, segmental artery, and interlobular artery of right and left kidneys in both groups|
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| Discussion|| |
Over the past decade, the incidence of childhood-onset type-1 diabetes mellitus has significantly increased, particularly in children younger than 5 years .
Diabetic nephropathy is defined as persistent proteinuria greater than 500 mg/24 h, or albuminuria greater than 300 mg/24 h .
Diabetic nephropathy remains the leading cause of end-stage renal disease. However, only a minority of patients with type-1 diabetes mellitus progress to end-stage renal disease .
Evaluation of vascular resistivity at different sites of the renal parenchyma may suggest functional or structural changes within the kidneys and could provide useful diagnostic and prognostic information .
Ultrasonic and Doppler imaging has also traditionally been used in the assessment of renal disease. Not only does Doppler ultrasonography detect renal macroscopic vascular abnormalities but it also identifies changes in blood flow at the microvascular level .
The aim of this study was to evaluate the diagnostic value of renal duplex in evaluation of early renal hemodynamics alteration in type I diabetic patient.
Our study shows that there are significant differences in the RI of MRA (P = 0.001), RI of SA (P < 0.001), and RI of ILAs (P < 0.001), which were significantly higher in the diabetic group.
In other words, children with diabetes had significantly greater RI values than age-matched healthy controls, although all the RI values were smaller than or equal to 0.70, which is the usually accepted boundary value for healthy adults and children older than 6 years (but not younger children), and these findings agree with Kuzmic et al. , Murat et al. , and Pelliccia et al. .
Youssef et al.  found that there is significant increase in the mean renal RI in children with type-1 diabetes mellitus over age-matched healthy children [0.64 ± 0.55 (0.54–0.75) vs. 0.58 ± 0.28 (0.54–0.63); P < 0.05].
Our study shows that there is significant positive correlation between RI of MRA (r = 0.756), SA (r = 0.791), and ILAs (r = 0.757) and duration of diabetes in the diabetic group, which agrees with some randomized studies [Figure 3].
|Figure 3: Correlation between resistive index (RI) of main renal, segmental, and interlobar arteries and duration of diabetes in the diabetic group.|
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Youssef et al.  stated that there was positive correlation between the duration of diabetes and mean RI. Multiple regression analysis revealed that the RI values in patients with DM were significantly affected by creatinine clearance, age [Table 3], and duration of type-1 diabetes, which agrees with Ishimura et al. .
|Table 3: Mean and SDs of resistive index values for each age (Kuzmic et al. )|
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Our study showed that there is no significant correlation between RI of MRA (r = 0.222), SA (r = 0.305), and ILAs (r = 0.361), and HbA1C among the diabetic group, which is in contrast to some randomized studies.
Youssef et al.  found that there is a positive correlation between HbA1c and mean RI. There are reports suggesting a general decreasing incidence of diabetic vascular complications related to improved and more intensive insulin treatment, resulting in better quality of diabetes care. This might, at least, lead to less severe complications in the future, as stated by Amin et al. .
Moreover, Abou El-Ella et al.  found that the HbA1c test is an early detector of diabetes mellitus among high-risk groups. Prediabetes occurs because of the interaction between genetic and environmental factors. Controlling the environmental factors by proper family counseling can delay and even inhibit the emergence of diabetes.
Our study found that there is significant positive correlation between RI of MRA (r = 0.515), SA (r = 0.635), and ILAs (r = 0.532), and serum creatinine level (mg/dl) among the diabetic group, and this finding agrees with some randomized studies.
Sari et al.  found that the intrarenal RI shows a high level of correlation with serum creatinine concentration and creatinine clearance rate, and it can be used as a predictor in patients with advanced clinical diabetic nephropathy. Intrarenal RI does not offer any advantage over serum creatinine concentration and creatinine clearance rate in patients with early-stage diabetic nephropathy with normal renal function.
Our study showed, there is significant correlation of serum creatinine with age among control and diabetic groups (r = 0.873), and it is same number in diabetic and control groups because mean age is the same in both groups and this finding agrees with some studies.
Pottel et al.  found that serum creatinine level increases with age, equal for boys and girls, up to 14 years, with a much steeper slope for boys than girls between 14 and 20 years. They show that the serum creatinine level-age pattern is constant between 20 and 70 years with a mean of 0.90 mg/dl (0.63–1.16 mg/dl) for men and 0.70 mg/dl (0.48–0.93 mg/dl) for women. In older than 70 years, serum creatinine starts to slowly increase again.
However, females and older people usually have less muscle mass and, consequently, lower production of creatinine, and lower serum creatinine level than males and younger people. These age and sex differences are taken into account by most equations of estimation of glomerular filtration rate as stated by Shimada et al. .
The study shows that renal Doppler indices did not vary between the right and left kidneys in healthy individuals as well as in the diabetic group. This is in agreement with the findings of Milovanceva-Popovska and Dzikova  and Murat et al.  that failed to detect any difference in RI between the kidneys. Interestingly, Yildirim et al.  found no inequality in flow velocity waveform indices, including PSV, EDV, RI, and PI of the renal arteries on both sides.
In contrast with our findings, Kliewer et al.  revealed PSV, among the renal Doppler parameters for early systole, as a varying parameter between the kidneys. However, they concluded that such asymmetry in PSV was clinically insignificant.
Our study found that albumin/creatinine ratio in mg/mmol (P < 0.001) is significantly higher among the diabetic group, and there is a positive correlation between the RIs or renal and intrarenal arteries and the albumin/creatinine ratio and these findings agree with some studies.
Abd El Dayem et al.  revealed significant positive correlation between the RIs in the intrarenal (segmental, arcuate, and interlobar) arteries and both KIM-1 and albumin/creatinine ratio (P = 0.02 and 0.05, respectively) in diabetics. Moreover, Saif et al.  revealed a significantly positive correlation between the RIs in the intrarenal arteries and the albumin/creatinine ratio in type I diabetic patients whereas other studies found no correlation between increased RI and microalbuminuria as stated by Abd El Ghaffar et al.  and Youssef et al. .
Further studies should also be done focusing on RI of renal arteries and other renal biomarkers such as neutrophil gelatinase-associated lipocalin (NGAL), liver-type fatty acid binding protein (L-FABP), and urine levels of kidney injury molecule-1 (Kim-1) in Type I diabetic patients as early and specific markers for detection of diabetic nephropathy.
| Conclusion|| |
Renal Doppler studies can play an essential role in prevention and early detection of diabetic nephropathy (DN) in patients with diabetes mellitus (type I) patients in correlation with other laboratory findings. Early detection of DN will prompt proper therapy and proper prognosis for those patients.
RI of the MRA, SA, and ILA arteries are sensitive but not specific as early detection of DN, so we do not recommend using the RI of MRA, SA, and ILA alone as a solely predictor of DN but in combination with renal biomarkers for prediction of diabetic nephropathy.
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Conflicts of interest
There are no conflicts of interest.
| References|| |
Saif A, Soliman NA, Abdel-Hameed A. Early evaluation of renal hemodynamic alterations in type I diabetes mellitus with duplex ultrasound. Saudi J Kidney Dis Transpl 2010; 21
Savino A, Pelliccia P, Schiavone C, Primavera A, Tumini S. Serum and urinary nitrites and nitrates and Doppler sonography in children with diabetes. Diabetes Care 2006; 29
Fiorini F, Barozzi L. The role of ultrasonography in the study of medical nephropathy. J Ultrasound 2007; 10
Viazzi F, Leoncini G, Derchi LE, Pontremoli R. Ultrasound Doppler renal resistive index: a useful tool for the management of the hypertensive patient. J Hypertens 2014; 32
Loredana M, Francesco CH. Diabetic nephropathy. In: Ellis D, editor. Text book of pediatric nephrology. 6th
ed. Avner: William E. Ed Harmon and Patrick Niaduet publishers; 2009. pp. 1199–1217.
Gross JL, de Azevedo MJ, Silveiro SP, Canani LH, Caramori ML, Zelmanovitz T. Diabetic nephropathy: diagnosis, prevention, and treatment. Diabetes Care 2005; 28
Kuzmic AC, Brkljacic B, Ivankovic D, Galesic K. Doppler Sonographic renal resistance index in healthy children. Eur Radiol 2000; 10
Murat A, Akarsu S, Ozdemir H, Yildirim H, Kalender O. Renal resistive index in healthy children. Eur J Radiol 2005; 53
Pelliccia P, Savino A, Cecamore C, Primavera A, Schiavone C, Chiarelli F. Early changes in renal hemodynamics in children with diabetes: Doppler sonographic findings. J Clin Ultrasound 2008; 36
Youssef DM, Fawzy FM. Value of renal resistive index as an early marker of diabetic nephropathy in children with type-1 diabetes mellitus. Saudi J Kidney Dis Transpl 2012; 23
Ishimura E, Nishizawa Y, Kawagishi T. Intrarenal hemodynamic abnormalities in diabetic nephropathy measured by duplex Doppler sonography. Kidney Int 1997; 51
Amin R, Widmer B, Prevost AT. Risk of microalbuminuria and progression to macro-albuminuria in a cohort with childhood onset type 1 diabetes: prospective observational study. BMJ 2008; 336
Abou El-Ella SS, Tawfik MA, Hewait SA. Early detection of diabetes mellitus in high-risk children. Menoufia Med J 2014; 27
Sari A, Dinc H, Zibandeh A, Telatar M, Gumele HR. Value of resistive index in patients with clinical diabetic nephropathy. Invest Radiol 1999; 34
Pottel H, Vrydags N, Mahieu B, Vandewynckele E, Croes K, Martens F. Establishing age/sex related serum creatinine reference intervals from hospital laboratory data based on different statistical methods. Clin Chim Acta 2008; 396
Shimada A, Kimura H, Oida K. Serum CETP status is independently associated with reduction rates in LDL-C in pitavastatin-treated diabetic patients and possible involvement of LXR in its association. Lipids Health Dis 2016; 15
Milovanceva-Popovska M, Dzikova S. Doppler ultrasonography: a tool for nephrologists – single centre experience. Prilozi 2008; 29
Yildirim H, Gungor S, Cihangiroglu MM, et al
. Doppler studies in normal kidneys of preterm and term neonates. J Ultrasound Med 2009; 24
Kliewer MA, Hertzberg BS, Keogan MT, Paulson EK, Freed KS, DeLong DM, et al
. Early systole in the healthy kidney: variability of Doppler US waveform parameters. Radiology 1997; 205
Dayem SAE, Bohy AEME, Hamed M, Ahmed S. Follow up of value of the intrarenal resistivity indices and different renal biomarkers for early identification of diabetic nephropathy in type 1 diabetic patients. Open Access Maced J Med Sci 2017; 5
Abd El Ghaffar S, El Kaffas K, Hegazy R, Mostafa M. Renal Doppler indices in diabetic children with insulin resistance syndrome. Pediatr Diabetes 2010; 11
[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2], [Table 3]