Hereditary proteinuria syndromes and mechanisms of proteinuria.

N Engl J Med 2006;354:1387-401. Copyright © 2006 Massachusetts Medical Society. The inherited forms of proteinuria comprise a heterogeneous group of rare renal diseases in which glomerular dysfunction and proteinuria are prominent. Despite the rarity of hereditary proteinuria syndromes, genetic, biochemical, and structural studies of these diseases have made important contributions to our knowledge of how the normal glomerular filter works and the mechanisms of proteinuria. The courses of these diseases can vary. Some patients present with severe proteinuria and congenital nephrotic syndrome, whereas others have only moderate proteinuria and focal segmental glomerulosclerosis. Regardless of its cause, the disease often progresses to end-stage renal disease. Classification of these syndromes has been difficult because the age at onset and the clinical manifestations vary, but in recent years, considerable progress has been made in determining the genetic causes of these conditions. There can be overlap between the diseases: mutations in the same gene can lead to either congenital nephrotic syndrome or focal segmental glomerulosclerosis. Therefore, we refer to these diseases as hereditary proteinuria syndromes. From a clinical standpoint, it is important to know that some hereditary proteinuria syndromes respond to therapy, whereas others do not. For this reason, genetic testing, which is available for some hereditary proteinuria syndromes, should be performed whenever possible. Knowledge of the mechanisms of glomerular filtration and proteinuria is still limited, but this field is the subject of intensive and productive research. This review summarizes recent progress in studies of the glomerular filter and the causes of hereditary proteinuria syndromes.