A 62-year-old woman with type 2 diabetes on metformin and hypertension on lisinopril develops acute kidney injury (serum creatinine 3.2 mg/dL, eGFR 18 mL/min/1.73 m²) after starting an NSAID for arthritis pain. She is at risk for metformin-associated lactic acidosis (MALA). Which investigation is most appropriate to confirm the diagnosis and assess severity?

Explanation

## Pathophysiology of MALA Metformin-associated lactic acidosis occurs when: 1. **Reduced renal clearance** of metformin (AKI from NSAID-induced prerenal injury or direct tubular toxicity) 2. **Accumulation** of metformin in plasma and tissues 3. **Impaired lactate clearance** by the kidneys, leading to **lactic acidosis** **Key Point:** MALA is a metabolic emergency characterized by elevated plasma lactate (>5 mmol/L), low pH, and high anion gap metabolic acidosis. ## Investigation of Choice **High-Yield:** Arterial blood gas (ABG) with serum lactate and anion gap calculation is the gold standard because it: - **Directly measures** arterial pH and HCO~3~^−^ (confirms metabolic acidosis) - **Quantifies lactate** (diagnostic threshold: >5 mmol/L for MALA) - **Calculates anion gap** using: $AG = [Na^+^] - ([Cl^-^] + [HCO_3^-])$ - Normal AG = 8–16 mEq/L - Elevated AG (>12) + elevated lactate = **high anion gap metabolic acidosis** (pathognomonic for MALA) - **Guides severity** and urgency of dialysis ## Why ABG + Lactate is Diagnostic **Clinical Pearl:** - Serum lactate >5 mmol/L + pH <7.35 + elevated AG = **MALA confirmed** - Mortality is 30–50% even with treatment; early recognition is critical - ABG also shows respiratory compensation (low PaCO~2~) via Kussmaul respiration ## Management Implications - Immediate **hemodialysis** (removes metformin and lactate) - Discontinue metformin - Supportive care (fluid resuscitation, vasopressors if shock) [cite:Harrison 21e Ch 297; KD Tripathi 8e Ch 12]