Diagnostic Value of Doppler Ultrasound for Early Prediction of Reversibility of Acute Kidney Injury in Septic ICU Patients
Conditions: Acute Kidney Injury, Sepsis, Renal Resistive Index
Sponsor: Aristotle University Of Thessaloniki

 Aristotle University of Thessaloniki 
 G. Papanikolaou General Hospital of Thessaloniki 
GREECE 
 
 
 
 
Study No. NT001 - Doppler Ultrasound for Prediction of Reversibility of Acute 
Kidney Injury in Septic ICU Patients 
 
 
 
 
 
 
Study protocol and statistical analysis plan 
 
 
 
 
 
 
 
 
 
Thessaloniki, 5 October 2017 
 
 
 
 

Study protocol and statistical analysis plan 
 
This was a prospective observational cohort study with unselected, consecutive septic patients being 
included. Thirty-two adult septic patients hospitalized in a general intensive care unit were studied 
during the first 24h of treatment and after the discharge from the ICU setting. The unit has a capacity of 
15 beds and is located in a large tertiary hospital in northern Greece. The study was conducted from 
March to August 2017. The protocol had the approval of the ethics committee of the hospital. Subjects 
were included if they developed sepsis plus AKI during their hospitalization in the ICU, regardless of 
the underlying cause. The presence of Acute Kidney Injury was determined according to the KDIGO 
guidelines, i.e. at least stage 1 AKI. The categorization of AKI as transient or persistent was  
determined by the normalization of the kidney function after the administration of appropriate therapy 
and support in the ICU environment and after 3 days of hospitalization. For the purpose of the study all 
consecutive patients suffering from sepsis were included, with the exception of those surviving less 
than three days, in order to determine whether they had AKI (persistent or not). 
 
After the determination of sepsis, patients were divided into 3 distinct groups: Group 1 included the 
patients without progression to AKI, Group 2 included the patients with transient AKI and Group 3 
comprised of the patients with persistent kidney injury. For every group a series of functional 
physiological parameters were recorded or measured: Age, sex, mortality, hospitalization days in ICU, 
baseline Urea and Creatinine, SOFA and APACHE II scores upon admission to ICU, Lactates, Urine 
Urea and Creatinine, Fractional Excretion of Sodium (FENa), the Urine Urea to Plasma Urea and the 
Urine Urea to Plasma Creatinine ratio, the Urine Potassium to Urine Sodium ratio, Plasma urea/ 
creatinine ratio, the Daily Diuresis and the Fluids Balance during the first 3 days of ICU stay and the 
Hematocrit. Other parameters recorded were related to the cardiac function as assessed by the heart 
ultrasound [Velocity-Time Integral calculated at the aortic valve (VTI) and the Cardiac Index (CI)], as 
well as respiratory parameters in mechanically ventilated patients (Respiratory Compliance, Tidal 
Volume - Vt, Oxygen Saturation of Hemoglobin – SaO2, PaO2 to FiO2 ratio) or circulatory system 
indexes, like Mean Arterial Pressure (MAP), heart rate (HR) and dosage of vasoactive agents. 
 
The US examinations were performed by three ICU medical doctors under the supervision of a senior 
consultant, experienced in abdomen US. A standard convex transducer for abdominal exploration was 
used for the identification of renal vasculature and the calculation of the resistive index. B-mode US in 
the posterior-lateral approach allowed localization of the kidneys and evaluation of renal parenchyma. 
In all patients, simultaneous recordings of color Doppler ultrasound for semi-quantitative evaluation of 
renal vasculature and pulse Doppler ultrasound for the calculation of RI were performed. The former 
led to a grading from 0 (no identifiable renal vasculature) to 3 (fully identifiable renal vessels up to the 
arcuate arteries) (Table 1). The Resistive Index is calculated employing the following formula: RI= 

[peak systolic velocity - minimum diastolic velocity] / peak systolic velocity. Assessment of both 
kidneys was performed and at least three values for RI were obtained from each kidney. The average 
value from all the measurements was considered the final value for every case. 
 
Table 1: Color-Doppler for a semi-quantitative evaluation of intra-renal vascularization 
 
Stage 
Quality of renal perfusion by color-Doppler 
0 
Unidentifiable vessels 
1 
Few vessels visible near the hilum 
2 
Hilar and interlobar vessels in most of the renal parenchyma 
3 
Renal vessels identifiable until the arcuate arteries in the field of view 
 
 
Statistics 
 
The study parameters were tested for compliance with the normal distribution with the Kolmogorov- 
Smirnoff test. For the comparison between the 3 groups of patients the one-way Analysis of Variance 
(ANOVA) was utilized. The Bonferroni post-hoc analysis was employed to reveal statistical 
differences in means between the three groups of patients. For discrete variables, the x2 test was used. 
Correlations between various parameters were explored using the Pearson’s correlation test. The 
identification of independent variables predicting persistent AKI was based on multivariate logistic 
regression analysis. Finally, the creation of the ROC curve for the calculated RI values was used to 
determine the ideal cut-off value of the RI concerning the prediction of persistent AKI in this pool of 
participants, rendering the respective sensitivity and specificity characteristics. 
 
Statistical significance level was set to 0.05. All statistical analyses were performed using the SPSS 
v.15 (IBM) statistical software.