A 52-year-old man with chronic kidney disease (eGFR 28 mL/min/1.73 m²) presents with fatigue and palpitations. His wife reports he has been taking an ACE inhibitor for hypertension for the past 6 months. Laboratory investigations reveal: Na⁺ 138 mEq/L, K⁺ 6.8 mEq/L, Cl⁻ 104 mEq/L, HCO₃⁻ 22 mEq/L, creatinine 2.1 mg/dL. ECG shows peaked T waves and prolonged PR interval. Which of the following mechanisms best explains the hyperkalemia in this patient?

Explanation

## Pathophysiology of Hyperkalemia in CKD with ACE Inhibitor ### Mechanism of K⁺ Retention **Key Point:** ACE inhibitors block angiotensin II formation, which normally stimulates aldosterone secretion. In the setting of reduced GFR, this dual insult (decreased aldosterone + reduced filtration) causes severe hyperkalemia. ### Role of Aldosterone in K⁺ Homeostasis Aldosterone acts on the collecting duct principal cells to: 1. Increase Na⁺ reabsorption via epithelial sodium channels (ENaC) 2. Enhance K⁺ secretion via ROMK (renal outer medullary potassium) channels 3. Maintain the negative potential gradient necessary for K⁺ secretion When aldosterone is suppressed (by ACE inhibitor), K⁺ secretion is impaired. ### Why This Patient Is at High Risk | Factor | Effect on K⁺ | | --- | --- | | CKD (eGFR 28) | Reduced GFR → ↓ filtered load of K⁺ | | ACE inhibitor | ↓ Angiotensin II → ↓ Aldosterone secretion | | Combined effect | Severe ↓ K⁺ excretion (both renal and hormonal) | **Clinical Pearl:** The combination of CKD + ACE inhibitor/ARB is one of the most common iatrogenic causes of hyperkalemia in clinical practice. ECG changes (peaked T waves, prolonged PR interval) indicate cardiac membrane hyperexcitability. ### Renal Potassium Handling Algorithm ```mermaid flowchart TD A[K⁺ intake and GFR]:::outcome --> B{Aldosterone level?}:::decision B -->|Normal| C[Normal K⁺ secretion in CD]:::action B -->|Low: ACE-I/ARB| D[↓ ENaC activity<br/>↓ K⁺ secretion]:::urgent C --> E[K⁺ homeostasis maintained]:::outcome D --> F[Hyperkalemia]:::urgent F --> G[ECG changes:<br/>peaked T, prolonged PR]:::outcome ``` **High-Yield:** In CKD patients on ACE inhibitors, K⁺ > 5.5 mEq/L warrants dose reduction or discontinuation of the RAAS inhibitor. **Mnemonic: RAAS-K** — Renin-Angiotensin-Aldosterone System suppression → K⁺ retention (in CKD). [cite:Harrison 21e Ch 280]