A 42-year-old man from Delhi presents with nephrotic syndrome (proteinuria 8 g/day, serum albumin 2.1 g/dL, edema). Kidney biopsy shows the pattern marked **A** in the diagram—sclerosis affecting approximately 30% of glomeruli, with involvement of only segments of those affected glomeruli. Light microscopy shows hyalinosis in some lobules. Which of the following is the most likely diagnosis?

Explanation

## Why Focal segmental glomerulosclerosis (FSGS) is right The histopathologic pattern marked **A**—sclerosis affecting <50% of glomeruli (focal) and only segments of those glomeruli (segmental)—is the defining pathologic hallmark of FSGS. The presence of hyalinosis (marked **C**) in some lobules further supports this diagnosis. FSGS is the most common cause of primary nephrotic syndrome in adults in India and globally. The clinical presentation of nephrotic syndrome with proteinuria, hypoalbuminemia, and edema in a middle-aged Indian patient is consistent with FSGS, which typically presents more abruptly and with more severe proteinuria than minimal change disease. (Robbins 10e Ch 20) ## Why each distractor is wrong - **Minimal change disease (MCD)**: While MCD also presents with nephrotic syndrome, it shows NO visible glomerular abnormality on light microscopy—the glomeruli appear normal. The focal segmental sclerosis pattern marked **A** is incompatible with MCD. MCD is more common in children and has better steroid responsiveness (~80-90% vs ~40-50% in FSGS). - **Membranoproliferative glomerulonephritis (MPGN)**: MPGN presents with a lobular/nodular appearance on light microscopy with basement membrane duplication and endocapillary or extracapillary proliferation. The focal segmental sclerosis pattern marked **A** is not characteristic of MPGN. MPGN typically presents with hematuria and hypertension more prominently than pure nephrotic syndrome. - **Diffuse proliferative glomerulonephritis (DPGN)**: DPGN (as in lupus nephritis or post-infectious GN) shows proliferation in >50% of glomeruli with endocapillary or extracapillary changes. The segmental sclerosis pattern marked **A** affecting <50% of glomeruli is not consistent with diffuse disease. DPGN typically presents with hematuria, RBC casts, and hypertension. **High-Yield:** FSGS = **focal** (<50% glomeruli) + **segmental** (partial glomerular involvement) sclerosis; most common primary nephrotic syndrome in Indian adults; ~40-50% steroid-responsive; ~50% progress to ESRD in 5-10 years. [cite: Robbins 10e Ch 20]