Treatment of primary focal segmental glomerulosclerosis.

children. After serial section analysis, the difference Introduction was greater, with a figure of 48.0±6.6% in adults, contrasting with 23.2±7.4% in children, in whom focal Focal segmental glomerulosclerosis (FSGS) is just one lesions were smaller, more segmental and peripheral. of several deceptive denominations for a glomerulopaSuch findings might indicate that FSGS is not exactly thy that in fact is a podocyte disease [1]. A host of the same condition according to age, which might conditions are liable to injure the glomerular epithelial explain differences in response to treatment. cells and lead to FSGS [2]. Therefore, it should be The clinical picture of FSGS comprises two forms stressed that FSGS is a lesion, not a disease. From that apparently correspond to different entities. The this standpoint, the topic ‘Treatment of FSGS’ may first is characterized by insidious onset of low-grade be considered a misnomer, as the podocyte disease proteinuria not reaching nephrotic levels. In a series that is the initial event in the natural history of FSGS of 492 adult cases, Korbet et al. [7] identified 32% of is rarely, if ever, accessible to specific treatment. Once cases with this presenting feature of FSGS. The develthis initial cellular insult has led to the focal and opment of this form is slow and, in our experience, segmental glomerular lesions, the goal of treatment proceeds for decades before it leads to ESRF. The is essentially to control proteinuria and hopefully to second form, which represents two-thirds of cases, is arrest or slow the development of glomerular fibrosis marked by a rapid or even sudden onset of a fullin order to limit progression to end-stage renal failure blown picture of nephrotic syndrome. Initial renal (ESRF). biopsy usually finds lesions of FSGS, but the glomeruli Here we shall distinguish non-nephrotic from may be normal by light microscopy and immunofluonephrotic primary FSGS, focusing mainly on the latter. rescence, leading to the misdiagnosis of minimal change disease. Resistance to corticosteroid therapy should FSGS: description and natural history suggest performing a repeat renal biopsy after completing an adequate course of treatment. In most cases, repeat biopsy discloses transition from minimal The pathological description of FSGS has evolved over changes to FSGS [8], an ominous finding concerning the years. Conventional descriptions refer to lesions further prognosis, as indicated below. Conversely, in initially localized within segments of the glomerular some rapidly developing forms of nephrotic FSGS, tuft lobules. Pathological variants include hilar, perisevere cellular lesions of collapsing glomerulopathy are pheral and glomerular tip lesions [3], and some pubfound in most but not all glomeruli. It has been shown lications contend that some of these localizations entail recently that in these cellular variants of FSGS, podobetter prognosis than others, which has not been cytes undergo a process of cell transdifferentiation, confirmed [4]. Recent histological techniques of threelosing their normal phenotype and expressing macrodimensional (3-D) glomerular reconstruction have shed phagic markers [9]. new light on the concept of ‘focal’ and ‘segmental’ Treatment of non-nephrotic FSGS is not codified. sclerosis. Fuiano et al. [5] have shown by 3-D reconThe absence of nephrotic syndrome and slow developstruction that the glomerular lesions of FSGS are more ment, in addition to ignorance of pathophysiology, widely distributed in the glomerular tufts than determight explain this lack of information in the medical mined by conventional 2-D microscopy, and proposed literature. However, non-nephrotic FSGS certainly to change the term ‘FSGS’ to ‘DSGS, diffuse segmental glomerulosclerosis’. Using the same approach, Fogo excludes an aggressive therapeutic approach based et al. [6 ] found that on initial section, the percentage on corticosteroids or any form of immunosuppressive of sclerosis was 31.5±6.8% in adults vs 11.7±5.7% in regimen. Conservative treatment should consist of dietary measures aimed at reducing overweight, controlling hyperlipidaemia, when present, and normalizing blood Correspondence and offprint requests to: Alain Meyrier, Service de pressure with angiotensin-converting enzyme (ACE) Nephrologie and INSERM U 430, Hopital Broussais, 96 Rue Didot, 75674 Paris Cedex 14, France. inhibitors. Whether AT1 antagonists are endowed with