Breaking old and new paradigms regarding urinary sodium in acute kidney injury diagnosis and management

Urinary sodium (NaU) is one of the oldest parameters used in the evaluation of azotemia and oliguria. Over the past years, however, it has progressively been considered as obsolete and useless, especially in sepsis. It is common sense that NaU frequently does not correlate well with global renal blood flow. If intrarenal microcirculatory changes are more important in acute kidney injury (AKI) than changes in global renal blood flow, we speculate that decreases in NaU may be viewed as a possible marker of microcirculatory impairment in the kidneys. Recent findings by our group (some not yet published) in which sodium retentive capacity is preserved until advanced stages of AKI and the observation of decreases in NaU preceding increases in creatinine bring us to conclude that the new paradigm of abolishing NaU consideration from daily approaches to managing patients at risk for AKI must be reevaluated.


The emergence of the new paradigm
In 2006, a systematic review [8] revealed that NaU values were widely variable within and between studies with no consistent values to distinguish normal kidney function, pre-renal azotemia and ATN. A contemporaneous experimental study inducing hyperdynamic sepsis revealed progressively lower levels of NaU [6]. It was hypothesized that the sodium retentive state was due to loss of glomerular fi ltration pressure. In fact, progressive decreases in NaU were accompanied by decreases in creatinine clearance. Th e authors concluded that NaU was not a reliable marker of renal perfusion (breaking the old 'pre-renal' paradigm). Since then, a new paradigm has emerged: NaU must not be used as a diagnostic tool in AKI [7].

Reasons why the new paradigm is misleading
Dissociation between macrohemodynamics and microhemodynamics in sepsis is common. Th is phenomenon is the possible explanation for apparently paradoxical increases in the sublingual tissue partial pressure of carbon dioxide (P sl CO 2 ; a marker of microcirculatory stagnation) in parallel with increasing cardiac output during sepsis [9]. Hence, a similar phenomenon could explain the paradox between an increased renal blood fl ow and low NaU levels. Glomerular perfusion pressure, not total renal blood fl ow, is the main determinant for NaU levels. In infl ammatory states, low glomerular perfusion pressure may occur in the presence of increased renal blood fl ow, with activation of sodium-retaining Abstract Urinary sodium (NaU) is one of the oldest parameters used in the evaluation of azotemia and oliguria. Over the past years, however, it has progressively been considered as obsolete and useless, especially in sepsis. It is common sense that NaU frequently does not correlate well with global renal blood fl ow. If intrarenal microcirculatory changes are more important in acute kidney injury (AKI) than changes in global renal blood fl ow, we speculate that decreases in NaU may be viewed as a possible marker of microcirculatory impairment in the kidneys. Recent fi ndings by our group (some not yet published) in which sodium retentive capacity is preserved until advanced stages of AKI and the observation of decreases in NaU preceding increases in creatinine bring us to conclude that the new paradigm of abolishing NaU consideration from daily approaches to managing patients at risk for AKI must be reevaluated. Although tubular injury is an early event in AKI [10], most studies still found low fractional excretion of sodium levels in this context [11,12]. We may conclude that too much injury is needed to impair the global tubular capacity to retain sodium. Recent unpublished results by our group also suggest that sodium retention is progressively more intense with increases in AKI severity except in very advanced stages (AKI Network stage 3); we hypothesize that extensive tubular injury jeopardized sodium reabsorption. In our fi ndings, such progressive decreases in NaU began earlier than increases in creatinine, as described in a case report [13].

Reasons why many previous NaU studies are fl awed
Most studies regarding NaU in AKI have three main limitations. First, NaU is measured only once instead of sequentially; as previously demonstrated [6,14], NaU responds fast to acute hemodynamic alterations so that relative alterations in it may be more relevant than an isolated NaU value. It is important to remember that NaU has a very large physiological range that depends on numerous variables. Of these, the most likely responsible for an abrupt decrease in NaU value is a decrease in glomerular fi ltration rate. Second, NaU is still treated as a categorical variable [15]; the dynamism of NaU is lost if NaU is viewed as '<20 mEq/L' or '>40 mEq/L' . Th is view is overly simplistic and unreliable. Th ird, NaU is usually assessed only in the presence of oliguria or azotemia. In a recent article [16], we suggested that urinary electrolyte measurement may alert for the presence of AKI development before increases in creatinine or oliguria. In that study, patients who developed AKI in the fi rst 4 days after admittance to the ICU had signifi cantly lower NaU values at admission.

Microcirculation: a possible bridge between renal blood fl ow and NaU
Low NaU values in AKI can be a sign of microcirculatory impairment in the kidneys. We have observed many critically ill patients with very low NaU levels on the day that renal replacement therapy was initiated. Th is is not surprising in the context of multiple organ failure, which may be caused by systemic microcirculatory failure. From this perspective, the lower the NaU, the greater the microcirculatory stress. On the other hand, high NaU values are more diffi cult to interpret. Th ere is no well established normal range for NaU. In a study including 10 healthy volunteers, the mean NaU was 104 ± 48 mEq/ L [17]. We have also found median NaU values above 100 mEq/L at ICU admission in patients who did not develop AKI during the study period [16]. However, high NaU values can be found in patients with AKI receiving diuretics or in advanced AKI stages.

Conclusion
As for many other monitoring parameters in critical care medicine, the fi rst step in defi ning NaU utility in daily practice is to understand properly what it is saying to us and in which contexts. New paradigms regarding this subject should be carefully reevaluated.