Urine sodium concentration to predict fluid responsiveness in oliguric ICU patients: a prospective multicenter observational study

In our study, most patients with transient oliguria did not increase their cardiac output or their urine output after the fluid challenge. Low urine sodium concentration and FENa⁺ were not reliable predictors of fluid responsiveness. Although FEurea and uUrea were different in the CRs and the CNRs, the differences were not clinically relevant for predicting fluid responsiveness.

In routine practice, low urine output often leads to performing fluid challenge in ICU patients. This is based on the hypothesis of a systemic hemodynamic contribution to low renal blood flow and low urine output [11, 12]. However, physiological grounds exist to consider oliguria a poor marker of hypovolemia or low intravascular volume [6]. Shock, pain, and the perioperative period are associated with alteration of intrarenal hemodynamics [13, 14] and activation of the RAAS, leading to antinatriuresis and antidiuresis [15, 16]. Our study shows that oliguria with low urine Na⁺ concentration in normotensive ICU patients may not reflect hypovolemia in a large proportion of patients. Hence, fluid challenge may not translate into an increase in cardiac output or urine output.

Low uNa⁺ has long been proposed as a biomarker of prerenal failure as well as low intravascular volume status and/or low cardiac output. However, a low urine Na⁺ concentration is a biomarker of RAAS activation that may be triggered by various factors. Urine biomarkers have previously been shown to inaccurately predict persistent or transient AKI [17]. In a multicenter study, Pons et al. showed that urine biochemistry parameters, including FENa⁺ and FEurea, did not predict the rapid reversibility of AKI [18]. Regulation of urine output and renal Na⁺ handling involves many other factors, including tubular cell function and systemic inflammation [19, 20]. Therefore, many factors unrelated to intravascular volume and cardiac output may affect urine output and renal Na⁺ handling, including tubular Na⁺ channel expression [6]. It therefore remains very difficult to recommend the use of urinary biomarkers to predict fluid responsiveness in critically ill patients. Urine biomarkers may still be indicative of tubular function and renal hemodynamics, but these points were not addressed in the present study. In our study, the influence of renal perfusion pressure on renal hemodynamics was reduced by excluding the patients with mean arterial pressure 65 mmHg. However, urine Na⁺ remained poorly predictive of fluid responsiveness (either cardiac output or renal response) in our patients. Clinicians should therefore rely on other markers of fluid responsiveness when deciding whether to initiate a fluid challenge in patients with oliguria. Nevertheless, we acknowledge that our definition of renal responsiveness was arbitrary, relying on the Kidney Disease: Improving Global Outcomes (commonly referred to as KDIGO [21]) definition with a urine output threshold of 0.5 ml/kg/h. Some patients showed a relative increase of urine output after the fluid challenge, albeit below this threshold.

Our study has several limitations. First, the sample size was small. However, the sample size was sufficient to detect a good predictive value of the biomarker. This hypothesis can be rejected on the basis of our results. The low rate of inclusion could be explained by several factors. Our patients had to be both oliguric and hemodynamically stabilized, which may have limited the number of patients eligible for inclusion. Second, they had to be off drugs that interact with renal sodium handling (e.g., diuretics). Third, monitoring of cardiac output or an echocardiography-certified physician was required to monitor stroke volume during the fluid challenge. Altogether, these points may limit the external validity of the results. Nevertheless, urine Na⁺ was not strongly associated with fluid responsiveness. A poor predictive value for fluid responsiveness was observed.

Stroke volume was evaluated with different tools. These tools have been used with acceptable accuracy in monitoring stroke volume [2]. Most important, the same monitor was used for each patient, limiting bias. Urine biochemistry analyses were not centralized in a single laboratory. This may have generated variability, but it also increased the extrapolation of our results. Norepinephrine infusion was required in some patients, affecting intrarenal hemodynamics. However, Bellomo et al. observed that restoring renal perfusion pressure with norepinephrine decreased renal resistance and increased renal conductance in sepsis [22]. Finally, regarding the AKI definition, we were aware that estimating baseline serum creatinine may have introduced bias into the classification. However, estimation of baseline serum creatinine in ICU patients with no available baseline values remains a challenge, with no consensus on the method of obtaining a surrogate.