What is the clinical significance of metabolic acidosis, severe impaired renal function, and elevated anion gap?

From the Guidelines

Metabolic acidosis with severe impaired renal function and elevated anion gap is a life-threatening condition that requires immediate attention and management to prevent further complications and improve patient outcomes. The clinical significance of this condition is multifaceted, involving increased oxidation of branched chain amino acids, protein degradation, and decreased albumin synthesis, as noted in the clinical practice guidelines for nutrition in chronic renal failure by the National Kidney Foundation 1.

Key Considerations

• Metabolic acidosis is associated with increased morbidity and mortality in patients with chronic renal failure (CRF) or those undergoing maintenance dialysis (MD) 1.
• The presence of an elevated anion gap suggests an increase in unmeasured anions, which can be due to various causes including lactic acidosis, ketoacidosis, or other organic acidemias.
• Severe impaired renal function, as indicated by elevated creatinine and blood urea nitrogen levels, suggests a critical reduction in kidney function, which can lead to the accumulation of waste products and electrolyte disturbances.

Management

• Normalization of serum bicarbonate levels should be a priority, with a goal of maintaining levels at or above 22 mmol/L, as recommended by the National Kidney Foundation 1.
• This can be achieved through higher dialysate bicarbonate concentrations or oral supplementation with bicarbonate salts, such as sodium bicarbonate, typically at a dose of 2 to 4 g/d or 25 to 50 mEq/d 1.
• Close monitoring of electrolytes, particularly potassium, is crucial to prevent hyperkalemia, a common complication of severe kidney failure.
• Investigation into the underlying cause of kidney injury is essential to guide specific management and prevent further deterioration.

Outcome Improvement

• Correction of metabolic acidosis has been associated with improved outcomes, including increased serum albumin, decreased protein degradation rates, and increased plasma concentrations of branched chain amino acids and total essential amino acids 1.
• Prompt management of metabolic acidosis and severe impaired renal function can help prevent life-threatening complications, such as uremic encephalopathy, pericarditis, or electrolyte disturbances, ultimately improving patient morbidity, mortality, and quality of life.

From the Research

Clinical Significance of Metabolic Acidosis

• Metabolic acidosis is a frequently encountered laboratory finding in daily clinical practice, and rapid pH correction is almost always preferred and necessary while performing workup to identify the causative factors 2.
• Severe impaired renal function can lead to metabolic acidosis, and treatment strategies require careful identification of the cause of the acute kidney injury (AKI), relying on both clinical history and laboratory data 3.
• Elevated anion gap is a common feature of metabolic acidosis, and it can be caused by various factors, including lactic acidosis, which can be treated with hemodialysis, continuous renal replacement therapy (CRRT), and bicarbonate replacement 2.

Consequences of Metabolic Acidosis

• Metabolic acidosis can have substantial adverse effects, including development or exacerbation of bone disease, growth retardation in children, increased muscle degradation with muscle wasting, reduced albumin synthesis with a predisposition to hypoalbuminemia, resistance to the effects of insulin with impaired glucose tolerance, acceleration of the progression of chronic kidney disease (CKD), stimulation of inflammation, and augmentation of β(2)-microglobulin production 4.
• The presence of metabolic acidosis is associated with increased mortality, and treatment with sodium bicarbonate can improve kidney and patient survival in CKD patients 5.

Treatment of Metabolic Acidosis

• The administration of base to patients prior to or after initiation of dialysis can lead to improvement in many of the adverse effects of metabolic acidosis 4.
• Treatment of metabolic acidosis with sodium bicarbonate can delay the progression of CKD, and it is safe and improves kidney and patient survival in persons with CKD 3-5 without advanced stages of chronic heart failure 5.
• Hemodialysis and CRRT can be used to treat severe metabolic acidosis, especially in patients with frank renal failure and concurrent metformin use 2.