What is the primary step in managing an increased anion gap in patients with Acute Kidney Injury (AKI)?

From the Guidelines

The primary step in managing an increased anion gap in patients with Acute Kidney Injury (AKI) is to identify and treat the underlying cause of the metabolic acidosis, as recommended by the most recent guidelines and studies, including those published in 2020 and 2024 1. This typically begins with a thorough assessment to determine whether the increased anion gap is due to lactic acidosis, ketoacidosis, toxic ingestions, or uremic acidosis from the AKI itself.

• Key considerations include:
  • Improving tissue perfusion in lactic acidosis
  • Administering insulin and glucose for ketoacidosis
  • Using specific antidotes for toxic ingestions In cases where uremic acidosis from AKI is the primary driver, initiation of renal replacement therapy (RRT) such as hemodialysis may be necessary if the acidosis is severe (pH < 7.1-7.2) or if there are other indications for dialysis, as suggested by studies on the optimal management of AKI 1. While sodium bicarbonate (typically 50-100 mEq IV over 2-4 hours, or as a continuous infusion) may be used as a temporizing measure for severe acidosis (pH < 7.1), it should not replace addressing the underlying cause, as emphasized in the clinical guidelines for managing AKI 1. This approach is justified because metabolic acidosis in AKI can worsen kidney injury through inflammation and hemodynamic effects, while also causing systemic complications including cardiac dysfunction and insulin resistance, highlighting the importance of prompt and targeted intervention based on the most current evidence 1.

From the FDA Drug Label

In metabolic acidosis associated with shock, therapy should be monitored by measuring blood gases, plasma osmolarity, arterial blood lactate, hemodynamics and cardiac rhythm. Bicarbonate therapy should always be planned in a stepwise fashion since the degree of response from a given dose is not precisely predictable Initially an infusion of 2 to 5 mEq/kg body weight over a period of 4 to 8 hours will produce a measurable improvement in the abnormal acid-base status of the blood. Solutions containing sodium ions should be used with great care, if at all, in patients with congestive heart failure, severe renal insufficiency and in clinical states in which there exists edema with sodium retention.

The primary step in managing an increased anion gap in patients with Acute Kidney Injury (AKI) is to identify and treat the underlying cause of the acidosis.

• Bicarbonate therapy should be planned in a stepwise fashion, with careful monitoring of the patient's response to treatment.
• The initial dose of sodium bicarbonate is typically 2 to 5 mEq/kg body weight over a period of 4 to 8 hours, as stated in the drug label 2.
• However, in patients with severe renal insufficiency, solutions containing sodium ions should be used with great care, if at all, due to the risk of sodium retention and fluid overloading, as warned in the drug label 2.

From the Research

Causes of Increased Anion Gap in AKI

• The increased anion gap in patients with Acute Kidney Injury (AKI) can be caused by various factors, including lactic acidosis, ketones, uraemic acidosis, and toxin ingestion 3.
• Metabolic acidosis is a common complication in critically ill patients, and the correct identification of the cause is crucial for rational management 3.

Diagnosis of Increased Anion Gap in AKI

• The diagnosis of increased anion gap in AKI involves the measurement of serum electrolytes, including sodium, chloride, and bicarbonate, as well as the calculation of the anion gap 3.
• The anion gap can be calculated using the formula: Anion Gap = Sodium - (Chloride + Bicarbonate) 3.
• A high anion gap can indicate the presence of unmeasured anions, such as lactate, ketones, or other organic acids 3.

Management of Increased Anion Gap in AKI

• The management of increased anion gap in AKI involves the identification and treatment of the underlying cause, as well as the correction of any electrolyte imbalances 4.
• Conservative management, including fluid resuscitation and electrolyte replacement, should be attempted first, and renal replacement therapy or hemodialysis may be necessary in severe cases 4, 5.
• The use of renal replacement therapy, such as hemodialysis or continuous renal replacement therapy, can help to remove excess ions and correct electrolyte imbalances 5.

Prognosis and Outcome

• The presence of an increased anion gap in AKI has been associated with a higher risk of mortality and morbidity 6.
• A study using the MIMIC-III database found that a higher anion gap was a significant predictor of 30-day, 90-day, and 365-day all-cause mortality in critically ill patients with AKI 6.
• Regular monitoring of serum electrolytes, including the anion gap, is essential for the early detection and management of AKI and its complications 7.