IS FOCAL SEGMENTAL GLOMERULOSCLEROSIS REALLY FOCAL - DISTRIBUTION OF LESIONS IN ADULTS AND CHILDREN

The distribution of lesions of glomerulosclerosis, whether focal or di ffuse, has important implications for pathogenesis and potential thera peutic response. Determination of focal or diffuse nature of lesions f rom a single section, may, however, be misleading. We therefore evalua ted 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, ele ctron microscppy, and light microscopy that had >10 glomeruli and seru m creatinine <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 analysi s. 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 invo lved 31.5 +/- 6.8% of glomeruli in adults, contrasting only 11.7 +/- 5 .7% in children (P < 0.05). Complete serial section analysis was possi ble in 14.1 +/- 1.6 and 10.7 +/- 1.6 glomeruli in adults and children, respectively. After this serial section analysis, the percent of glom eruli involved by sclerosis increased to 48.0 +/- 6.6% in adults and 2 3.2 +/- 7.4% in children (P < 0.025). The pattern remained focal in al l but one case that had the highest serum creatinine. The greater incr ease in sclerosis after serial section analysis in children versus adu lts reflects the predominance of small peripheral, that is, more segme ntal, lesions in children than adults. These findings show that glomer ulosclerosis in FSGS indeed is focal at the time of biopsy; that is, s paring some glomeruli. Further, at the time of biopsy, the population of glomeruli involved by sclerosis is significantly higher in adults v ersus children, which has important implications for treatment and may possibly also reflect differences in pathogenesis.