How does prerenal Acute Kidney Injury (AKI) cause hyponatremia?

From the Guidelines

Prerenal Acute Kidney Injury (AKI) can cause hyponatremia due to the kidney's response to decreased perfusion, leading to sodium and water retention.

Pathophysiology of Prerenal AKI

• The major hemodynamic abnormality underlying functional kidney alterations in cirrhosis is splanchnic and systemic vasodilatation, which causes effective arterial underfilling 1.
• This leads to compensatory vasoconstrictor system activation (renin–angiotensin–aldosterone and sympathetic nervous systems) and results in kidney vasoconstriction that first conserves sodium and then water and finally reduces kidney blood flow to a level that impairs GFR 1.

Mechanism of Hyponatremia in Prerenal AKI

• In prerenal AKI, the kidney's response to decreased perfusion is to retain sodium and water, which can lead to hyponatremia 1.
• The fractional excretion of sodium (FENa) can be used to assess sodium handling in patients with AKI, with a low FENa (<1%) suggesting prerenal causes including volume depletion 1.
• However, the use of FENa has limitations, and fractional excretion of urea (FEUrea) may be a better discriminator between prerenal and structural causes of AKI 1.

Clinical Evaluation and Management

• Investigation of AKI in patients with cirrhosis should be directed to determining the cause of AKI, which can be due to hypovolemic causes, acute tubular necrosis, hepatorenal syndrome with AKI (HRS-AKI), or postrenal causes 1.
• The specific type of AKI should be identified through a careful history, physical examination, blood biochemistry, urine microscopic examination, urine chemistry, and selected urinary biomarkers, and renal ultrasound 1.

From the Research

Prerenal Acute Kidney Injury (AKI) and Hyponatremia

• Prerenal AKI is a common cause of hyponatremia, as seen in a study published in the Journal of Nephrology 2, where 12 out of 14 patients with AKI had prerenal origins.
• The pathophysiology of prerenal AKI involves decreased renal perfusion, which can lead to a decrease in glomerular filtration rate and subsequent hyponatremia 3.
• Prerenal mechanisms contributing to AKI may be transient and reversible, such as volume depletion, or more persistent, as observed with heart failure and liver disease 3.
• The reduction in glomerular filtration rate in prerenal AKI is largely mediated by reductions in nephron plasma flow and decreases in the glomerular ultrafiltration coefficient 3.

Relationship between Prerenal AKI and Hyponatremia

• A study published in PloS One found that pre-existing hyponatremia independently predicted AKI development and in-hospital mortality 4.
• The concurrence of AKI and hyponatremia is important pathophysiologically and for planning rational management for both disorders 2.
• Isotonic fluid replacement can correct both prerenal AKI and hyponatremia without leading to overly rapid correction of hyponatremia 2.

Pathogenesis of Prerenal AKI

• Prerenal AKI can be caused by renal hypoperfusion and ischemia due to decreased cardiac output, as well as reduction of absolute or relative circulating blood volume 5.
• Renal congestion is also a potential cause of AKI in patients with heart failure, leading to increased renal interstitial hydrostatic pressure and a reduction of the glomerular filtration rate 5.
• Adrenergic activity and angiotensin II are the dominant hormonal influences that impact the determinants of glomerular filtration in prerenal AKI 3.