**Core Concept**
Minimal change disease (MCD) is a type of nephrotic syndrome characterized by the loss of large amounts of protein in the urine. The pathophysiology of MCD involves changes in the glomerular filtration barrier, which normally allows water and small solutes to pass through while retaining larger molecules like proteins.

**Why the Correct Answer is Right**
The main cause of minimal change disease is the increase in the size of the pores in the glomerular basement membrane, specifically the podocyte slit diaphragm. Normally, these pores are tightly regulated, allowing only small molecules to pass through. In MCD, the increased pore size disrupts the glomerular filtration barrier, leading to the loss of albumin and other large proteins in the urine. This is due to the loss of the actin cytoskeleton and the slit diaphragm proteins (such as nephrin and podocin) that maintain the integrity of the podocyte slit diaphragm.

**Why Each Wrong Option is Incorrect**
**Option B:** The loss of negative charge on the membrane is associated with other types of glomerulonephritis, such as membranous nephropathy, but not minimal change disease.
**Option C:** The loss of cells is not a characteristic feature of minimal change disease, which is characterized by the presence of normal-appearing glomeruli on light microscopy.
**Option D:** Decreased circulation is not a direct cause of minimal change disease, although patients with MCD may have decreased renal function due to proteinuria and hypoalbuminemia.

**Clinical Pearl / High-Yield Fact**
MCD is the most common cause of nephrotic syndrome in children, and the presence of minimal glomerular changes on light microscopy is a hallmark of this condition. Treatment typically involves corticosteroids, which can induce remission in the majority of cases.

✓ Correct Answer: A. Increase in pore size