Settings and patients
A prospective observational study was performed in a 14-bed medical–surgical intensive care unit (ICU), from November 2013 to October 2014, approved by local ethics committee (Hospital das Clínicas, University of São Paulo, Brazil-Protocol Number 335.619). As the data were collected during standard routine care performed in the ICU, the same committee waived the need for informed written consent. Since previous data suggested an association between serum chloride and renal vascular resistance , we evaluated the association between these two variables in a pilot observation with the first 15 patients included. This analysis was planned before data collection, and it was necessary due to the lack of data regarding the association between chloride and renal RI. We observed a positive correlation between these two parameters (Spearman correlation, ρ = 0.348, p < 0.05). Thus, with α = 0.05 and a β = 0.10, we estimated a sample size of 83 patients .
Inclusion criteria were all patients admitted to the ICU with an expected length of stay longer than 72 h. Exclusion criteria were age under 18 years, pregnancy, known artery renal stenosis, chronic kidney disease defined by a glomerular filtration rate of less than 30 mL/min/1.73 m2, cirrhosis with hepatorenal syndrome, use of renin–angiotensin–aldosterone antagonists, absence of a vesical indwelling catheter during the study period, and AKI on renal replacement therapy (RRT) or with an expectation of RRT within 24 h.
Each patient included was studied within the first 24 h after ICU admission. The same operator performed renal RI daily until the third day after ICU admission, death, or RRT requirement, whichever occurred first. A fully trained investigator who performed the measurements was not in charge of the patients, and the physicians in charge were unaware of the results of the renal RI. RI was performed only after hemodynamic stabilization defined as the mean arterial pressure greater than 65 mmHg for more than 1 h without any fluid loading or any change in the rate of catecholamine infusion. The ventilator settings and sedative infusion rates (if applicable) were unchanged for at least 1 h before renal RI.
An ultrasound machine (GE Healthcare® LOGIQ P5, Wisconsin, USA) with a 4 MHz curved-array transducer was used. Renal RI was obtained from a posterolateral approach from the right kidney in all but three patients. B mode allowed kidney localization and detection of signs of chronic renal disease. An interlobar or arcuate artery was identified and then selected. The Doppler spectrum was considered optimal when at least three similar consecutive waveforms were visualized. The peak systolic velocity (Vmax) and the minimal diastolic velocity (Vmin) were determined by pulse wave Doppler. RI was calculated as (Vmax − Vmin)/Vmax. At least, three recordings were obtained from the selected arteries, and the mean of three RI was used to the analysis .
Patient demographics, SAPS 3 score , SOFA score , comorbidities, daily urine output and fluid balance, use of vasopressors, use of loop diuretics, use of mechanical ventilation, and renal replacement therapy requirement during the first 3 days of the ICU stay were recorded. Both ICU and hospital mortality were also recorded. Blood samples were collected routinely, once daily, just after renal RI measurements.
AKI diagnosis and reversibility
AKI was evaluated at admission and daily during the ICU stay; it was defined according to KDIGO criteria , which proposed AKI as any of the following: increase in serum creatinine (sCr) greater or equal to 0.3 mg/dL within 48 h; or increase in sCr to greater or equal than 1.5 times baseline that was known or presumed to have occurred within the prior 7 days; or urine output less than 0.5 mL/kg/h for 6 h. Baseline serum creatinine was defined as the lowest value in the previous 3 months before ICU admission. In the absence of known baseline sCr, the nadir of sCr after renal recovery was used. In the absence of renal recovery, baseline sCr was estimated by using the Modification of Diet in Renal Disease (MDRD) formula.
AKI’s reversibility was categorized as transient or persistent. Transient AKI was defined as a 50% decrease in sCr or normalization of urine output within 3 days. Persistent AKI was defined as persistent elevated sCr, oliguria for at least 72 h or need of RRT .
Continuous parametric and nonparametric variables were presented as the mean (standard deviation) and median (25th; 75th percentiles) and were compared using the t test and Mann–Whitney test, respectively. Categorical variables were expressed as absolute (n) and relative (%) frequency and were compared by the Chi-square test with Yates correction. Comparison between three groups was made using Kruskal–Wallis and ANOVA for nonparametric and parametric variables, respectively. Correlations tests were performed using the Spearman correlation coefficient.
A linear mixed model was applied to evaluate the association between renal RI values and the variables of interest and to account for repeated measures. Renal RI was assessed as a dependent variable, and hemodynamic data, SAPS 3, presence of sepsis, use of vasoactive drugs, age, AKI category (absent, transient or persistent), and laboratory values were evaluated as fixed covariates.
All analyses and graphs were generated using R project 3.0.2 (www.r-project.org) and SPSS Statistics 19 (Chicago, Illinois, USA). A p value of less than 0.05 was considered statistically significant in all cases.