Daily urinary urea excretion to guide intermittent hemodialysis weaning in critically ill patients

We conducted a retrospective single-center cohort study in a ten-bed medical ICU of a university hospital in France. This study was approved by our institutional review board (CPP Sud-Est 6 – IRB00008526 number 2015/CE90) in accordance with French regulations. The board waived the need for signed informed consent for patients included. All consecutive patients with AKI requiring RRT between January 2006 and December 2011 were screened. The inclusion criteria were patients with AKI older than 18 years treated with IHD for at least 7 days and four IHD sessions. The exclusion criteria were patients with a decision to forgo life-sustaining treatment, patients who had undergone renal transplantation, patients treated with continuous RRT at the time of weaning, chronic dialysis patients, and patients with urine output less than 100 ml/24 h before the last dialysis session in the ICU.

The criteria for initiation of RRT for AKI were at the discretion of the physician. The determinants usually used for initiation of RRT in our ICU were serum urea concentration greater than 25 mmol/L, serum potassium concentration greater than 6 mmol/L, metabolic acidosis with pH less than 7.15, and acute pulmonary edema due to fluid overload with diuretic resistance. Patients who required RRT were treated with IHD, in some cases preceded by continuous RRT. IHD was promoted when the metabolic disorders were severe. Continuous RRT was promoted when fluid overloading was very high. IHD sessions were performed with the AK 200 Ultra S machine (Gambro, Meyzieu, France) and APS (Asahi PolySulfone) biocompatible dialysis membranes (Hemotech, Ramonville Saint-Agne, France). Anticoagulation was achieved with unfractionated heparin or low molecular weight heparin. Continuous RRT was performed with predilution hemofiltration or postdilution hemodiafiltration (ratio of dialysate to postdilution effluent equal to 1:1). Anticoagulation of continuous RRT was achieved with unfractionated heparin. Vascular access was a temporary double-lumen dialysis catheter positioned in a femoral or internal jugular vein. No protocol was used to make the decision to cease hemodialysis treatment.

Data were collected from consulting patients’ medical records and the electronic databases of the ICU and the Department of Medical Biochemistry at our institution. They comprised baseline demographic characteristics, type of admission, severity of illness and comorbidity score, amine and mechanical ventilation use, baseline serum creatinine, starting and cessation dates of RRT in the ICU, weaning date in the ICU, and diuretic use. Baseline serum creatinine was defined as the lowest serum creatinine value in the year before RRT initiation. Baseline glomerular filtration rate (GFR) was estimated according to the Modified Diet in Renal Disease equation [22]. Severity of illness at ICU admission was assessed on the basis of the Simplified Acute Physiology Score II and Sequential Organ Failure Assessment (SOFA) score. Comorbidities were evaluated by McCabe score. Serum electrolyte, creatinine, and urea concentrations were measured daily at 0700 h. In addition, 24-h urine output values (from 0700 to 0700 h) were collected daily. Concentrations of electrolytes, creatinine, and urea from 24-h urine collections were measured at 0700 h. Daily urinary urea excretion was defined as the product of urine output over 24 h and urinary urea concentration. Urine output was adjusted for the patient’s body weight at ICU admission. A patient was considered weaned in the ICU when dialysis was stopped for at least 1 week. For weaned patients, concentrations of electrolytes, creatinine, and urea in the blood and urine and 24-h urine output values were recorded 2 days after the last dialysis session. This day was chosen because it is the moment at which the decision to stop or to continue IHD is usually made. For unweaned patients, the same data were collected on the day of the last dialysis session in the ICU. One month after ICU discharge, renal outcome was recorded. Renal outcome could be either chronic RRT or renal recovery. Renal recovery was complete if serum creatinine was less than 125 % of baseline creatinine and partial otherwise [23].

Statistical analysis was performed with Stata 13 software (StataCorp, College Station, TX, USA). The tests were two-sided, with a type I error set at α = 0.05. Variables were presented as medians (interquartile range) for continuous data and as the number of patients and associated percentages for categorical parameters. Comparisons between the weaned and unweaned groups were made by using χ² or Fisher’s exact tests for categorical variables and Student’s t test or the Mann–Whitney U test for quantitative parameters. Assumption of normality was assessed by using the Shapiro–Wilk test, and homoscedasticity was verified by using the Fisher-Snedecor test. To identify independent predictors of IHD weaning, a multivariate logistic regression analysis was performed with IHD weaning as the dependent variable. The interactions between factors were tested. All variables whose values were significantly different between the two groups were included. The predictive ability of urine output, urinary urea concentration, and daily urinary urea excretion was assessed with the area under the receiver operating characteristic curve (AUROC) method. Optimal diagnostic thresholds were determined by Youden’s index [1 − (sensitivity + specificity)]. AUROC curves were compared by using the DeLong method [24]. The sensibility, specificity, and accuracy (percentage of patients correctly classified in the weaned or unweaned groups) were compared by using Cochran’s Q test. Positive and negative predictive values were compared by using Fisher’s exact test.