Focal Glomerular Sclerosis (FQS)



FGS is a cause of the nephrotic syndrome in 10 to 20 per cent of children and young adults. The presentation is usually that of edema with heavy proteinuria.

In children, this disorder may be diagnosed as minimal change nephropathy (MCN) in the ab­sence of a renal biopsy. However, a number of clinical features tend to set focal glomerular scle­rosis apart from the more common minimal change lesion. The most striking difference is the steroid resistance of proteinuria in FGS. Only 10 to 15 per cent of patients with FGS remit with steroids, a number similar to the rate of sponta­neous remission, compared to a remission rate of more than 90 per cent in MCN. Microhematuria is common in FGS, and gross hematuria occa­sionally occurs. Hypertension and azotemia are present at the time of diagnosis in a majority of patients with FGS. Serum complement levels are normal. Tubular dysfunction (glycosuria, ami­noaciduria, and phosphaturia) is more often seen in this disorder than in other glomerular diseases.

The diagnostic feature of this glomerulopathy on light microscopy is the focal (only some glo­meruli involved) and segmental (only parts of each glomerulus affected) finding of hyalin scle­rosis in the absence of significant proliferation or necrosis. Typically, the deeper, juxtamedullary glomeruli are first affected and more superficial glomeruli remain normal. Hence, a superficial renal biopsy sample may be mistakenly identified as minimal change nephropathy. There is some predilection for the process to begin near the vas­cular stalk of the glomerulus. Late in the disease, global sclerosis of individual glomeruli and pro­nounced tubular atrophy are seen.

Immunofluorescence shows patchy deposits of IgM and C3 confined to areas of the glomeruli identified as sclerosed on light microscopy. The IgM is believed to be trapped nonspecifically in sclerotic glomeruli but not to be causally related to the development of FGS. On electron micros­copy, there are foamy cellular degeneration and hyaline sclerosis in affected areas, and deposits corresponding to the IgM seen by immunofluo­rescence are evident.
While remissions do occur, the overall course is one of continuous proteinuria with relentless progressionjo end-stage renal failure. Persistent, nephrotic-range proteinuria has a less favorable prognosis, with at least 50 per cent of these pa­tients having terminal renal failure at 10 years. Steroids do not influence the proteinuria to any significant degree and do not alter the progressive decrease in GFR. Recurrence in transplants does occur.