Is focal segmental glomerulosclerosis really focal? Distribution of lesions in adults and children

The distribution of lesions of glomerulosclerosis, whether focal or diffuse, has important implications for pathogenesis and potential therapeutic response. Determination of focal or diffuse nature of lesions from a single section, may, however, be misleading. We therefore evaluated the distribution of segmental glomerulosclerosis in patients with nephrotic syndrome and idiopathic focal segmental glomerulosclerosis (FSGS) by three-dimensional analysis. From our files, we identified all such biopsies with a diagnosis established by immunofluorescence, electron microscopy, and light microscopy that had > 10 glomeruli and serum creatine < 3.5 g/dl. Renal biopsies from 15 adults (9 women, 6 men, age 40.3 +/- 4.2 years and six children (2 girls, 4 boys, age 6.3 +/- 1.4 years) thus identified had sufficient serial sections for analysis. An average of 20.0 +/- 2.6 glomeruli in adults versus 25.2 +/- 3.9 in children were examined. Sclerosis assessed on a single section involved 31.5 +/- 6.8% of glomeruli in adults, contrasting only 11.7 +/- 5.7% in children (P < 0.05). Complete serial section analysis was possible in 14.1 +/- 1.6 and 10.7 +/- 1.6 glomeruli in adults and children, respectively. After this serial section analysis, the percent of glomeruli involved by sclerosis increased to 48.0 +/- 6.6% in adults and 23.2 +/- 7.4% in children (P < 0.025). The pattern remained focal in all but one case that had the highest serum creatinine. The greater increase in sclerosis after serial section analysis in children versus adults reflects the predominance of small peripheral, that is, more segmental, lesions in children than adults.(ABSTRACT TRUNCATED AT 250 WORDS)