What is the workup for non-anion gap acidosis (NAGA)?

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From the Guidelines

The workup for non-anion gap acidosis should begin with a thorough history, physical examination, and laboratory analysis, including serum electrolytes, arterial blood gas, urine pH, and urine electrolytes, as well as assessment of renal function with BUN and creatinine 1. When evaluating non-anion gap acidosis, it is essential to consider the underlying causes, which can include renal tubular acidosis (RTA), gastrointestinal bicarbonate loss, or renal tubular bicarbonate wasting.

  • Key laboratory tests include:
    • Serum potassium, chloride, bicarbonate
    • Urine pH and electrolytes
    • Calculation of the urine anion gap (UAG = Na+ + K+ - Cl-)
  • A positive UAG suggests renal tubular acidosis (RTA), while a negative UAG points to gastrointestinal bicarbonate loss or renal tubular bicarbonate wasting.
  • Additional tests should include assessment of renal function with BUN and creatinine, as outlined in the ACR Appropriateness Criteria for renal failure 1.
  • Evaluation for specific causes such as medication review for carbonic anhydrase inhibitors, diarrhea history, or signs of renal disease is also crucial.
  • For patients with unknown duration of kidney disease, a detailed history, physical examination, and laboratory analysis of blood and urine, in addition to imaging, may be necessary to determine the underlying cause of non-anion gap acidosis 1.

From the Research

Non-Anion Gap Acidosis Workup

The workup for non-anion gap acidosis involves a systematic approach to evaluate the underlying cause of the acid-base disturbance.

  • A complete clinical history and physical examination are critical initial steps to begin the evaluation process 2, 3.
  • Measuring serum electrolytes with a focus on potassium level, blood gas, urine pH, and either direct or indirect urine ammonium concentration are essential components of the workup 2, 3.
  • Evaluation of the electrolyte pattern to determine if a non-anion gap acidosis alone or a combined non-anion gap and high anion gap metabolic acidosis is present can help in making a presumptive diagnosis 3.
  • Examination of the serum potassium concentration to characterize the disorder as hyperkalemic or hypokalemic in nature can also aid in diagnosis 3.

Diagnostic Studies

If the initial information proves insufficient, additional diagnostic studies may be necessary, including:

  • Indirect estimates or direct measurement of urinary NH(4)(+) concentration 3.
  • Measurement of urine pH 2, 3.
  • Assessment of urinary HCO(3)(-) excretion 3.

Approach to Diagnosis

A systematic and cost-effective approach to the differential diagnosis of non-anion gap metabolic acidosis is recommended 3.

  • This approach involves considering the pathophysiology of the electrolyte pattern and the value and limitations of available diagnostic studies.
  • The use of sodium bicarbonate and its potential adverse effects in some conditions should also be considered 4.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Non-Anion Gap Metabolic Acidosis: A Clinical Approach to Evaluation.

American journal of kidney diseases : the official journal of the National Kidney Foundation, 2017

Research

Differential diagnosis of nongap metabolic acidosis: value of a systematic approach.

Clinical journal of the American Society of Nephrology : CJASN, 2012

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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