Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.15.1 (ACE)
 18,300 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Idiopathic focal segmental glomerulosclerosis (FSGS) is a common cause of nephrotic syndrome in pediatric and adult patients. Most children with FSGS do not respond to any form of therapy and progress to end-stage renal disease (ESRD). FSGS reoccurs in the transplanted kidney in approximately one third of initial transplants and in a substantially higher percentage of subsequent transplants once FSGS has recurred in an earlier transplant. Thus, FSGS is a disease with substantial morbidity. Over the past several years, the incidence of FSGS in adults and children appears to be increasing, particularly in certain racial groups and ethnic populations. Several recent studies in adult and pediatric patients suggest that the incidence of FSGS is increasing particularly in the black population. In addition, some studies have also demonstrated a more rapid progression of FSGS to ESRD in black patients compared to other ethnic groups. Racial and ethnic background is likely to have a substantial influence on the incidence and progression of FSGS in children and adults. It is likely that specific genes or a combination of genes influence the different clinical manifestations of FSGS in racial and ethnic groups. Genetic mutations in NPHS1 gene, which encodes nephrin, have been found to cause congenital nephrotic syndrome. Genetic mutations in the NPHS2 gene, which encodes podocin, recently have been shown to be strongly associated with a recessive form of steroid-resistant nephrotic syndrome. Mutations in the ACTN4 gene that encodes actinin 4 has also been associated with familial nephrotic syndrome. A role for ACE polymorphisms in the progression of FSGS has been found in some studies. Future investigations to identify polymorphisms that influence the development of FSGS, the progression of FSGS, and the response to therapy will greatly improve understanding of the pathogenesis and management of FSGS.
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PMID:Racial and ethnic differences in the incidence and progression of focal segmental glomerulosclerosis in children. 1473 May 45

Nephrotic syndrome (NS) is a clinical state characterized by massive proteinuria, hypoalbuminemia, and eventual edema formation. Although the mechanisms underlying this phenomenon are not yet fully clarified, it is well accepted that nephrin and podocin are involved in the development of proteinuria. The effects of early treatment with various antiproteinuric therapies on proteinuria and glomerular staining of nephrin and podocin in rats with experimental NS have not been previously studied. Proteinuria and glomerular nephrin and podocin immunofluorescence were examined in rat kidneys with adriamycin-induced NS and the effects of antiproteinuric drug therapies during 5 wk with enalapril, losartan, alone or in combination, omapatrilat, and mycophenolate mofetil on these parameters were assessed. Injection of adriamycin caused a significant increase in daily (from 21.8 +/- 1.4 to 983.1 +/- 45.8 mg/day, P < 0.01) and cumulative protein excretion (from negligible values to 22,490 +/- 931 mg, P < 0.001) during 5 wk. Early treatment with enalapril significantly decreased the daily (641.7 +/- 82.4 mg/day, P < 0.0023) and cumulative proteinuria (15,727 +/- 2,204 mg, P < 0.001). A similar effect, although to a lesser extent, was obtained after omapatrilat treatment: cumulative proteinuria was reduced to 18,706 +/- 1,042 mg, P < 0.001. In contrast, losartan treatment did not significantly influence the cumulative proteinuria that remained comparable (20,351 +/- 1,360 mg, P > 0.05) to that observed in untreated NS rats. Unexpectedly, when losartan was given in combination with enalapril, it abolished the beneficial effects of the latter. Pretreatment with mycophenolate mofetil exerted a moderate antiproteinuric effect, which appeared only during the last week of the experimental treatment. Nephrotic rats exhibited severe disruption of slit diaphragm structure as seen by rapid and profound loss of nephrin and podocin. Beneficial effects of enalapril, omapatrilat, and mycophenolate mofetil paralleled the preservation of nephrin, as determined immunohistochemically, and enabled prediction of significant antiproteinuric responses. Enalapril alone or in combination with losartan resulted in significant preservation of podocin. Pretreatment with enalapril, and to a lesser extent omapatrilat, is superior to losartan in reducing proteinuria in NS rats. A combination of ACE inhibitors with ANG II receptor blockers does not provide any advantageous antiproteinuric therapy in these animals. Nephrin loss is an indication of proteinuria in NS and the antiproteinuric effects of ACE inhibitors, vasopeptidase inhibitors, and mycophenolate mofetil attenuate this reduction. Not all the drugs which restore podocin reduce urinary protein in NS.
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PMID:Glomerular abundance of nephrin and podocin in experimental nephrotic syndrome: different effects of antiproteinuric therapies. 1594 45