Urine Nephrology Now: A Primer for Students in Nephrology
Acid-base homeostasis is fundamental to human physiology, with enzymatic function and metabolic processes requiring precise pH regulation. Deviations from the normal arterial pH range of 7.35-7.45 can have profound clinical consequences. It is critical to distinguish between acidemia/alkalemia (the state of the blood) and acidosis/alkalosis (the underlying process).
The bicarbonate buffering system is the primary extracellular buffer. Its governing equation is:
The power of this system lies in the independent physiological control of its components: the respiratory system regulates CO₂ (acid) and the kidneys control HCO₃⁻ (base). Respiratory compensation is rapid (minutes to hours), while renal compensation is slow (days).
Determine if acidemia (pH < 7.40) or alkalemia (pH > 7.40) is present.
Evaluate PCO₂ and HCO₃⁻. If the primary change aligns with the pH, it is the primary disorder.
Compensation is the body's attempt to normalize pH. Compensation is always incomplete; apparent overcompensation suggests a mixed disorder.
The normal anion gap range has narrowed to 8±2 mEq/L with modern analyzers. It's crucial to correct for albumin:
MUDPILES: Methanol, Uremia, DKA, Propylene glycol, Isoniazid/Iron, Lactic acidosis, Ethylene glycol, Salicylates.
NAGMA, or hyperchloremic metabolic acidosis, results from either the loss of bicarbonate or the addition of hydrochloric acid. The differential diagnosis can be organized using the mnemonic USEDCARP and further distinguished by the urinary anion gap (UAG).
The UAG serves as an indirect measure of urinary ammonium (NH₄⁺) excretion, which is the kidney's primary mechanism for eliminating acid. Since NH₄⁺ is excreted with Cl⁻, a high level of unmeasured NH₄⁺ (an appropriate response to acidosis) results in a high urine Cl⁻ and thus a **negative UAG**. Conversely, if the kidneys fail to excrete NH₄⁺, urine Cl⁻ will be lower, resulting in a **positive UAG**.
| UAG Result | Pathophysiology | Mnemonic (USEDCARP) | Specific Causes |
|---|---|---|---|
| Positive UAG | Renal Causes (Impaired renal acid excretion) |
Renal Tubular Acidosis (RTA) Addison's Disease Carbonic Anhydrase Inhibitors |
Type 1 (Distal) RTA Type 4 (Hypoaldosteronism) RTA Type 2 (Proximal) RTA Medications (Acetazolamide, Topiramate) |
| Negative UAG | Extra-Renal Causes (Bicarbonate loss, appropriate renal response) |
Ureteral Diversion Saline Administration (iatrogenic) Enteral/Parenteral Nutrition (amino acid cations) Diarrhea Pancreatic or Biliary Fistula |
Uretero-ileal conduit Excessive 0.9% NaCl infusion High-protein/cationic amino acid formulas Most common cause of NAGMA High-output GI losses |
The urinary anion gap is a valuable but indirect tool. Its use may decline in the future as direct measurement of urinary ammonium becomes more widely and rapidly available. Direct measurement provides a more precise quantification of the kidney's acid excretion response, eliminating the confounders that can affect the UAG (like the presence of other unmeasured anions such as ketoacids or drug metabolites).
Management should focus on treating the underlying causes rather than simply normalizing pH. Bicarbonate therapy is controversial and generally reserved for severe acidemia (pH < 7.15) with hemodynamic instability, certain intoxications, or severe hyperkalemia.