**Question:** A child comes with steroid resistant nephrotic syndrome secondary to FSGS, not responsive to methylprednisolone. What next should be given

A. Cyclophosphamide
B. Cyclosporine
C. Mycophenolate mofetil
D. Calcineurin inhibitors

**Correct Answer:** C. Mycophenolate mofetil

**Core Concept:** Steroid-resistant nephrotic syndrome (SRNS) is a clinical presentation in which steroid therapy fails to control the disease in patients with nephrotic range proteinuria. FSGS (Focal Segmental Glomerulosclerosis) is a common cause of SRNS.

**Why the Correct Answer is Right:** Mycophenolate mofetil (MMF) is an immunosuppressive agent that inhibits inosine monophosphate dehydrogenase (IMPDH), a key enzyme in de novo purine synthesis. This leads to suppression of T-cell proliferation and activation, which is beneficial in SRNS, particularly in cases like FSGS where immune-mediated injury is a significant component.

**Why Each Wrong Option is Incorrect:**

A. Cyclophosphamide: This is a cytotoxic agent that primarily induces cell cycle arrest and apoptosis, which may not be as effective in suppressing immune response as MMF in FSGS.

B. Cyclosporine: Cyclosporine is an immunosuppressive agent that blocks calcineurin-mediated T cell activation. However, it is less effective than MMF in FSGS, and its use may be associated with nephrotoxicity and hypertension risks.

C. Calcineurin inhibitors (Cyclosporine): These drugs inhibit calcineurin, a calcium-dependent serine/threonine protein phosphatase, which is involved in T cell activation, but MMF has a more direct immunosuppressive effect on T cells and is generally considered a better choice for FSGS cases.

D. Calcineurin inhibitors (Tacrolimus): Similar to cyclosporine, tacrolimus is a calcineurin inhibitor and may not be as effective in FSGS cases as MMF. Moreover, it carries a higher risk of nephrotoxicity and hypertension.

**Clinical Pearls:**

In cases of steroid-resistant nephrotic syndrome, particularly in FSGS, MMF is a more effective and safer option compared to calcineurin inhibitors. MMF's direct immunosuppressive effect on T cells and reduced nephrotoxicity make it a preferred choice in such cases.