The study sought a diagnostic clue to identify the group of pediatric patients with apparent minimal change disease who subsequently develop focal glomerular sclerosis (FGS). Review of all renal biopsy material at our institutions identified 42 pediatric patients who met the standard criteria for minimal change disease (MCD) on initial biopsies. Of those, 10 deteriorated clinically and on rebiopsy showed focal glomerular sclerosis (FGS). The initial renal biopsies of these 10 patients were analyzed morphometrically to determine the mean glomerular tuft area (GA). The results were compared to those of the remaining 32 patients whose subsequent benign clinical course was consistent with MCD, and to randomly selected, age-matched autopsy controls without renal disease (CONT, N = 10). The mean age was comparable among the three groups studied. Separate groups of adult (N = 12) and pediatric (N = 18) patients with initial biopsies with FGS were also studied. The initial biopsy of pediatric patients who subsequently showed FGS (rebiopsy performed on average 3.3 years later) had an average GA of 13.5 × 10-3 mm2, 76% larger than glomeruli from children with MCD (7.7 × 10-3 mm2, P < 0.0005) and 62% larger than CONT (8.4 × 10-3 mm2, P < 0.005). Patients with FGS on initial biopsy, whether adult or pediatric, also had significantly larger GA than the age-matched MCD or CONT groups. Evaluation of GA in all the 42 pediatric biopsies with initial MCD further showed that in 23 patients GA was equal to or smaller than the CONT average. Of these, one (4%) was found at the rebiopsy to have FGS. Fifteen patients had GA 1.00 to 1.75× the CONT average; five (33%) of these were found at the rebiopsy to have FGS. Finally, four had GA >1.75× the CONT average at the initial biopsy, all of whom (100%) were found to have FGS at the rebiopsy. The presence of glomerular hypertrophy in biopsies of apparent MCD, therefore, appears to be a highly specific indicator of increased risk for progression to FGS. The data are supportive of the view that the subset of MCD which develops FGS represents a distinctive entity in which pathophysiologic mechanism(s) promoting glomerular hypertrophy are imposed.
