Urine biochemistry assessment in the sequential evaluation of renal function: Time to think outside the box

Abstract

Urine biochemistry (UB) remains a controversial tool in acute kidney injury (AKI) monitoring, being considered to be of limited value both in terms of AKI diagnosis and prognosis. However, many criticisms can be made to the studies that have established the so called "pre-renal paradigm" (used for decades as the essential physiological basis for UB assessment in AKI) as well as to more recent studies suggesting that UB has no utility in daily clinical practice. The aim of this article is to describe our hypothesis on how to interpret simple and widely recognized urine biochemical parameters from a novel perspective, propose the rationale for their sequential assessment and demonstrate their usefulness in AKI monitoring, especially in the critical care setting.

Keywords: acute kidney injury; electrolytes; fractional excretion of potassium; monitoring; renal microcirculatory stress; urine; urine biochemistry; urine sodium.

FIGURE 1

Schematic representations of sodium handling by the nephron in distinct scenarios with high sodium load, a condition frequently seen in critically ill patients. Panel (A) represents a state with no renal microcirculatory stress (RMS) where high sodium load generates high urine sodium concentration (NaU), commonly above serum sodium concentration; panel (B) illustrates how sodium accumulates in the body in the setting of RMS due to a combination of low sodium filtration and avid sodium tubular reabsorption, which may lead to very low NaU levels; panel (C) represents a similar scheme to panel (B) except for significant tubular damage and/or the administration of diuretics, both of which jeopardize sodium tubular reabsorption. In this case, NaU levels are also depleted, comparatively higher to panel (B), but not as high as in panel (A) due to lower sodium filtration. GFR, glomerular filtration rate; RAA, renin-angiotensin-aldosterone; CO, cardiac output; SIRS, systemic inflammatory response syndrome.

FIGURE 2

Suggested approach to evaluate renal function at hospital/ICU admission using simple and feasible blood and urinary parameters. Urine sodium concentration (NaU) values between 40 and 140 mEq/L are of uncertain significance when measured at a single time point and should be obtained sequentially. Abrupt decreases in NaU suggest renal microcirculatory stress (RMS) development and risk of acute kidney injury (AKI). SCr, serum creatinine; sUr, serum urea; sNa, serum sodium; sK, serum potassium; KU, spot urine potassium concentration; CrU, spot urine creatinine concentration; FeK, fractional excretion of potassium; UO, urine output; CKD, chronic kidney disease.

FIGURE 3

Active investigation for the presence of renal microcirculatory stress (RMS), the initial stage of acute kidney injury (AKI) development. Very low or plummeting urine sodium concentration (NaU) is the hallmark of RMS. The fractional excretion of potassium (FeK) may help to work out the meaning of intermediate values of NaU (40–140 mEq/L) and the subsequent risk of AKI development. Systemic inflammatory response syndrome (SIRS), low cardiac output (CO), and nephrotoxins (iodide contrast/non-steroidal anti-inflammatory drugs/myoglobin, etc.) are potential and frequent causes of RMS. Very high NaU (>140 mEq/L) suggests absence of RMS/AKI or resolving RMS/AKI.

FIGURE 4

Urine biochemistry behavior after renal microcirculatory stress (RMS) has been triggered by a renal insult (macro or microcirculatory). Abrupt decreases in urine sodium concentration (NaU) as well as increases in the fractional excretion of potassium (FeK) occur before augmentation in serum creatinine (sCr). NaU value after acute kidney injury (AKI) diagnosis is quite variable because it depends on the magnitude of the reduction in glomerular filtration rate (GFR) in combination with the magnitude of tubular damage and impairment of tubular sodium reabsorption, as well as some degree of tubular sodium backleak (“??” represents NaU variability and unpredictability in the Figure). Nonetheless, in the context of AKI, NaU is not expected to reach very high values (>140 mEq/L). These values would only be found after renal function recovery. 1, 2, and 3 correspond to progressive stages of AKI severity.