**Core Concept**
The question is testing the pharmacological principle of diuretic action, specifically the mechanism of action of different classes of diuretics. The kidneys play a crucial role in regulating electrolyte and water balance, and diuretics work by either increasing sodium and water excretion or reducing reabsorption in the kidneys.

**Why the Correct Answer is Right**
Eplerenone is a potassium-sparing diuretic that works by antagonizing the mineralocorticoid receptor in the collecting duct, thereby reducing sodium reabsorption and potassium secretion. Unlike other diuretics, eplerenone does not need to be present in the tubular lumen to exert its diuretic effect. Instead, it acts on the mineralocorticoid receptor, which is located in the cell membrane.

**Why Each Wrong Option is Incorrect**
* **Option A:** Chlorthiazide is a thiazide diuretic that works by inhibiting the sodium-chloride cotransporter in the distal convoluted tubule, which requires it to be present in the tubular lumen.
* **Option B:** Acetazolamide is a carbonic anhydrase inhibitor that works by inhibiting carbonic anhydrase in the proximal convoluted tubule, which requires it to be present in the tubular lumen.
* **Option C:** Mannitol is an osmotic diuretic that works by increasing the osmotic pressure in the tubular lumen, which requires it to be present in the tubular lumen.

**Clinical Pearl / High-Yield Fact**
It's essential to remember that potassium-sparing diuretics like eplerenone can cause hyperkalemia, especially when used in combination with other potassium-sparing agents or in patients with renal impairment.

**✓ Correct Answer: D. Eplerenone**