Giving urine biochemistry a second chance in acute kidney injury monitoring

Table 1 Sequential values of serum creatinine, diuresis, and urine biochemical parameters during acute kidney injury development and recovery¹

Parameter	Day1	Day2	Day3	Day4	Day5	Day6	Day7	Day8	Day9
sCr (mg/dL)	1.7	3.9	4.4	4.5	4.4	4.0	3.4	3.2	2.6
KU (mEq/L)	-	15.8	6.9	6.6	6.1	7.0	5.7	17.9	-
CrU (mg/dL)	-	105	49	45	47	47	35	62	-
KU/CrU ratio	-	0.15	0.14	0.15	0.13	0.15	0.16	0.29	-
Diuresis /24 hours (mL)	-	3380	5620	7100	8180	8300
2-hour excreted mass of creatinine (mg/hour)							227.5
2-hour measured CrCl (mL/min)							111.5

¹A 30-year-old, 100 kg, muscular male was admitted to the intensive care unit due to suspected intraoperative ischemic alterations detected in cardiac monitoring during an elective otorhinolaryngologic surgery. He developed postoperative Kidney Disease: Improving Global Outcomes stage 3 acute kidney injury that was attributed to the use of anti-inflammatory drugs. The very low urinary potassium (KU) was compatible with polyuria (KU decreases with urine output increase), and the very low KU/urinary creatinine (CrU) ratio indicated a disproportionate increase in CrU, which indicated an increased mass of excreted creatinine at day 7 after surgery (normal: 0.5-1.0 mg/kg/hour). The measured creatinine clearance (CrCl) on that same day demonstrated a recovered glomerular filtration rate but a still significantly increased serum creatinine (sCr). We concluded that renal recovery occurred around D2, but it took some days to equilibrate creatinine excretion with creatinine production (leading to sCr stabilization around 4.5 mg/dL) and, in the subsequent days, elimination of the exceeding mass of creatinine that rapidly accumulated in the muscular patient´s body (leading to decreases in sCr). The patient received 3-5 L of crystalloids every day to prevent dehydration. However, we hypothesized that polyuria could be the result of hydration in a patient with an already recovered glomerular filtration rate.

CrU: Urinary creatinine concentration; KU: Urinary potassium concentration; sCr: Serum creatinine; CrCl: Creatinine clearance.

Table 2 Basic differences between the traditional and urine biochemical approaches for acute kidney injury monitoring

Traditional approach	Urine biochemical approach
sCr and UO are the main monitoring tools. AKI may be diagnosed based on increases in sCr or decreases in UO, independently from each other	sCr is a late AKI monitoring tool because it is the result of creatinine accumulation in the body; Decreases in CrU excretion may be considered an earlier marker of renal dysfunction, and the mass of excreted creatinine should be monitored
Oliguria is considered renal dysfunction	Oliguria is considered dysfunctional when it jeopardizes creatinine excretion; “Permissive oliguria” is defined as a decrease in UO that is counterbalanced by proportional increases in CrU, keeping the excreted mass of creatinine stable and preventing increases in sCr
Urine electrolyte assessment is made after AKI diagnosis and helps to distinguish pre-renal from renal AKI (functional vs structural AKI) in a single-point NaU assessment	Urine electrolyte assessment is made before sCr alterations and identifies RMS, which is characterized by significant decreases in NaU due to avid sodium retention; Sequential assessment is needed to properly observe this phenomenon
Very low NaU in the presence of AKI is a marker of low RBF	Significant acute decreases in NaU are an alert sign of RMS development and risk of AKI and may occur independently of volemic status, particularly in systemic inflammatory states such as sepsis, trauma, or after surgery
Low FeNa and low FeUr in the presence of AKI are also markers of pre-renal AKI	FeK is more relevant than FeNa and FeUr; FeK increases before sCr in AKI development; The KU/CrU ratio, included in the formula for FeK, is a simple marker of adequacy between UO and CrU; A high KU/CrU ratio points towards impaired creatinine excretion leading to subsequent increases in sCr due to systemic creatinine accumulation

AKI: Acute kidney injury; FeK: Fractional excretion of potassium; FeNa: Fractional excretion of sodium; FeUr: Fractional excretion of urea; KU/CrU: Urinary potassium (mEq/L)/urinary creatinine concentration (mg/dL); NaU: Urinary sodium concentration; RBF: Renal blood flow; RMS: Renal microcirculatory stress; sCr: Serum creatinine; UO: Urine output.