Since the ACE gene deletion polymorphism is a known risk factor for progressive glomerulosclerosis in chronic renal diseases, we have investigated the relationship between the ACE genotypes and the development of renal scarring after APN.
African Americans with arterionephrosclerosis who possess two APOL1 risk variants more often lack obsolescent glomerulosclerosis and have greater degrees of (solidified and disappearing) glomerulosclerosis, thyroidization-type tubular atrophy, and microcystic tubular dilation than patients with fewer than two risk variants.
Discrimination of these disparate disorders has the potential to eradicate primary forms of glomerulosclerosis that are associated with APOL1 renal-risk variants.
We show that mice with podocyte-specific expression of either APOL1 risk allele, but not of the G0 allele, develop functional (albuminuria and azotemia), structural (foot-process effacement and glomerulosclerosis) and molecular (gene-expression) changes that closely resemble human kidney disease.
Available evidence strongly supports that APOL1 renal-risk variants associate with glomerulosclerosis in African Americans, which then causes secondary hypertension, not with essential hypertension per se.
Discovery of the apolipoprotein L1 gene (APOL1) association with focal segmental glomerulosclerosis, human immunodeficiency virus (HIV)-associated nephropathy, lupus nephritis, sickle cell nephropathy, and solidified glomerulosclerosis, as well as more rapid failure of transplanted kidneys from donors with APOL1 renal-risk genotypes, has improved our understanding of nondiabetic nephropathy.
In contrast, genetic association between the apolipoprotein L1 (APOL1) gene and several severe nondiabetic forms of kidney disease in African Americans approach Mendelian inheritance patterns and account for a large proportion of glomerulosclerosis in populations of African ancestry.
Therefore, to investigate the mechanism of Wt1 R394W-induced renal failure, the expression of genes whose deletion leads to glomerulosclerosis (NPHS1, NPHS2, and CD2AP) was quantitated.
However, ACE2 generates angiotensin 1-7, which may protect the kidney by attenuating the effects of angiotensin II, since deletion of the Ace2 gene leads to glomerulosclerosis in mice, and pharmacologic inhibition of ACE2 exacerbates experimental diabetic nephropathy.
In this study, we describe a mouse model combining type 1 diabetes with activation of the renin-angiotensin system (RAS), which develops robust kidney disease with features resembling human DN: heavy albuminuria, hypertension, and glomerulosclerosis.
Thus, inhibition of the renal renin-angiotensin II-aldosterone system with angiotensin-converting enzyme inhibitor, angiotensin II type 1 receptor blocker or selective aldosterone inhibitor indirectly suppresses NADPH oxidase reducing renal ROS, proteinuria and glomerulosclerosis.
We tried to assess the influence of the -2578 C/A and -1154 G/A polymorphisms in the regulatory region of the vascular endothelial growth factor gene upon progression of three primary chronic glomerulonephritides (minimal change disease/focal and segmental glomerulosclerosis, membranous nephropathy, immunoglobulin A nephropathy).
A region of chromosome 22 which includes APOL1 and MYH9 genes was recently identified as a risk locus for non-diabetic forms of kidney disease, including idiopathic and HIV-associated focal segmental glomerular sclerosis and kidney disease clinically attributed to hypertension among African Americans.
MYH9-related variants were posited to be the probable, but not necessarily the definitive, causal variants as a result of impressive statistical evidence of association, renal expression, and a role in autosomal dominant MYH9 disorders characterized by progressive glomerulosclerosis (Epstein and Fechtner syndromes).
Although polymorphisms in the MYH9 gene on chromosome 22 are strongly associated with HIVAN, as well as with idiopathic focal segmental glomerulosclerosis and global glomerulosclerosis (historically labeled "hypertensive nephrosclerosis"), the majority of HIV-infected patients who are genetically at risk from MYH9 do not appear to develop severe kidney disease.
The nonmuscle myosin heavy chain 9 gene (MYH9) is associated with a spectrum of kidney diseases in African Americans, including idiopathic focal global glomerulosclerosis historically attributed to hypertension, idiopathic focal segmental glomerulosclerosis, and the collapsing variant of focal segmental glomerulosclerosis [HIV-associated nephropathy (HIVAN)].
Moreover, in one patient a new de novo TRPC6 mutation was associated with a rare severe form of childhood collapsing glomerulosclerosis with rapid progression to uremia.
Rare mutations in nephrosis 2 (NPHS2), encoding podocin, are found in patients with familial and sporadic steroid-resistant nephrotic syndrome and focal segmental glomerular sclerosis.
Therefore, to investigate the mechanism of Wt1 R394W-induced renal failure, the expression of genes whose deletion leads to glomerulosclerosis (NPHS1, NPHS2, and CD2AP) was quantitated.