Focal Segmental Sclerosis Research Articles

The significance of focal sclerotic lesions of glomeruli in children

To establish the relationship between the type of focal sclerotic lesion of glomeruli and the development of progressive renal disease, the clinical courses of 20 children with focal segmental and 7 with focal global sclerosis were analyzed. Only five patients, all of them with focal segmental sclerosis, did not have the nephrotic syndrome, although all had proteinuria. Results suggest that patients with focal global sclerosis have a course identical to that of children with the minimal lesion form of nephrotic syndrome: onset in early childhood, response to steroid therapy, and a relapsing, nonprogressive course. Focal segmental sclerosis, in constrast, is characterized by older age at onset, high incidence of nephritic symptoms, lack of response to steroid therapy, and a progressive course with histologic and functional deterioration. Since most published reports have not distinguished between these two entities, a more favorable prognosis in focal segmental sclerosis may be inferred than is actually the case.

Immunoglobulin A Nephropathy

Of 475 renal biopsles examined by immunofluorescence, IgA was seen located selectively in the glomerular mesangium of 18 patients. These patients were generally young men and had hematuria, only minimal proteinuria, and normal renal function. Glomerular lesions consisted of focal segmental capillary hypercellularity or sclerosis and mesangial thickening due to an increase in mesangial cells, matrix, and electron-dense deposits. Both IgG and C3 were frequently seen with IgA in the mesangium as was properdin in five of six cases, but C4, a component of the classical pathway of complement activation, was seen only infrequently. Serum IgA levels were elevated in many patients, but serum complement components were normal. These findings suggest a possible unusual immune pathogenesis with local mesangial binding and alternate pathway activation of complement.

Immunoglobulin A nephropathy

Of 475 renal biopsies examined by immunofluorescence, IgA was seen located selectively in the glomerular mesangium of 18 patients. These patients were generally young men and had hematuria, only minimal proteinuria, and normal renal function. Glomerular lesions consisted of focal segmental capillary hypercellularity or sclerosis and mesangial thickening due to an increase in mesangial cells, matrix, and electron-dense deposits. Both IgG and C3 were frequently seen with IgA in the mesangium as was properdin in five of six cases, but C4, a component of the classical pathway of complement activation, was seen only infrequently. Serum IgA levels were elevated in many patients, but serum complement components were normal. These findings suggest a possible unusual immune pathogenesis with local mesangial binding and alternate pathway activation of complement.

PROGNOSIS OF GLOMERULAR FOCAL SCLEROSIS IN CHILDREN

It is generally stated that focal sclerotic lesions of the glomeruli are associated with a poor prognosis. Nodistinction is usually mode between focal global sclerosis (complete hyalinization of affected glomeruli) and focal segmental sclerosis (hyalinization of only one area of the affected glomeruli). Seventeen children with focal sclerosis were surveyed to determine whether the type of lesion has prognostic significance. Four children, 3 male 1 female, presenting with nephrotic syndrome (NS) at the age of 13 to 19 months, were found to have focal global sclerosis. They all responded to prednisone therapy, relapsed frequently, and have normal renal function 9 to 14 years later. The 13 children with focal segmental sclerosis ranged in age from 1½ to 13 years; 7 were male and 6 female. Eleven presented with NS. Of these, 2 have died, 2 have received renal transplants, and 5 have mild to moderate decreases in renal function and show progression on subsequent biopsies. It is suggested that: 1) Focal global sclerosis is a disorder different from focal segmental sclerosis, presenting at an earlier age, responding to steroid therapy, and carrying a good prognosis. 2) Although focal segmental sclerosis is usually associated with NS, it can also present with only proteinuria and hematuria. Patients with this lesion do not respond to steroid therapy. Despite the fact that some patients maintain near-normal renal function over several years, all show histological deterioration.