**Core Concept**
The Glomerular Filtration Rate (GFR) is a critical measure of kidney function, representing the volume of fluid filtered from the renal glomeruli per unit time. Estimating GFR using plasma clearance values is essential in clinical practice to assess renal impairment and monitor the effectiveness of treatment.

**Why the Correct Answer is Right**
The correct answer is **Inulin**. Inulin is a naturally occurring polysaccharide that is freely filtered by the glomeruli without being reabsorbed or secreted by the renal tubules. As a result, its plasma clearance rate closely approximates the GFR, making it an ideal substance for estimating kidney function. Inulin clearance is considered the gold standard for measuring GFR, as it accurately reflects the glomerular filtration process.

**Why Each Wrong Option is Incorrect**
**Option A:** Creatinine is commonly used to estimate GFR, but it is not the best substance for this purpose due to its tubular secretion, which can lead to overestimation of GFR. While creatinine clearance is widely used in clinical practice, it is not as accurate as inulin clearance.

**Option B:** Iohexol is a non-ionic, water-soluble contrast agent that is used to measure GFR, but it is not the most commonly used substance for this purpose. Iohexol clearance is considered a reliable alternative to inulin clearance, but it is not as well-established in clinical practice.

**Option C:** Mannitol is an osmotic diuretic that is used to treat cerebral edema, but it is not used to estimate GFR. Mannitol is filtered by the glomeruli but is also reabsorbed and secreted by the renal tubules, making it a poor choice for measuring GFR.

**Clinical Pearl / High-Yield Fact**
Inulin clearance is considered the gold standard for measuring GFR, but it is rarely used in clinical practice due to the difficulty of administering inulin and measuring its clearance. Creatinine clearance is a more practical alternative, but its accuracy can be improved by using the Cockcroft-Gault equation or the MDRD equation to estimate GFR.

**Correct Answer:** A. Inulin