Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0344329 (collapse)
 28,634 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Renal failure is a known complication of HIV infection. The most common form is HIV-associated nephropathy, or HIVAN. It is characterized by high-grade proteinuria with rapid progression to end-stage renal disease. The kidneys of affected patients appear enlarged on ultrasonography. Histopathologically, there is focal segmental glomerulosclerosis with glomerular collapse. Before the era of HAART, patients with HIVAN had limited survival, although in some cases this was prolonged if dialysis was instituted. Over the past few years, isolated case reports have shown that patients with HIVAN will recover renal function following initiation of HAART. We report 3 patients believed to have HIVAN who exhibited marked improvement in renal function after treatment with a regimen comprising 2 nucleoside reverse transcriptase inhibitors and a protease inhibitor.
 ...
PMID:Resolution of renal failure after initiation of HAART: 3 cases and a discussion of the literature. 1196 39

Human immunodeficiency virus (HIV) associated nephropathy (HIVAN) is the most common disease delineated in biopsy series of patients with HIV infection and renal disease. Although the renal histologic lesions in patients with HIV infection present a spectrum of findings, several groups have emphasized characteristic clinical and pathologic features of HIVAN. Consensus has since been reached that HIVAN has a distinctive pathology, consistent with focal segmental glomerulosclerosis, but involving all subunits of the kidney. Several studies have linked the pathogenesis of focal glomerulosclerosis to abnormalities of the glomerular epithelial cell. Recent advances in molecular histologic studies and treatment link the pathogenesis of HIVAN to factors associated with the viral lifecycle. Cytopathic effects of HIV gene products, apoptosis mediated by HIV infection, the elaboration of chemokines and cytokines as a result of viral or host protein synthesis in patients with genetic susceptibility to nephropathy, and the subversion of the host metabolic and synthetic machinery by the virus might be sufficient to create a rapidly progressive disease. If HIV infects and has cytopathic effects on glomerular epithelial cells, and dysfunction of these cells is intimately related to the pathogenesis and progression of renal disease, a reasonable pathogenic mechanism for the development of HIVAN may be inferred. The similarities of HIVAN and the collapsing variant of focal segmental glomerulosclerosis pose the intriguing possibility that the latter is a viral illness as well. The disease is marked by glomerular sclerosis with varying degrees of collapse, tubular epithelial cell degeneration, simplification, microcystic dilatation, interstitial fibrosis and immune cell infiltration. At the level of electron microscopy, tubular reticular inclusions in renal endothelial cells are a typical, but not pathognomonic feature of HIVAN.
 ...
PMID:HIV-associated nephropathy: virologic issues related to renal sclerosis. 1295 44

The notable glomerular feature of human immunodeficiency virus (HIV)-associated nephropathy (HIVAN) is the collapse of the capillary tuft with marked glomerular epithelial cell hyperplasia. These data suggest a loss of normal podocyte function, which is associated with a loss of the podocyte differentiation markers, Wilm's tumor (WT-1), synaptopodin, podocalyxin, and common acute lymphoblastic leukemia antigen (CALLA). We have previously shown that HIV-1 expression can induce these changes in HIV-1 transgenic mice. To identify which HIV-1 gene product(s) are responsible for the phenotypic changes in podocytes, we created multiple mutated HIV-1 constructs and then pseudotyped them with vesticular stomatitis virus glycoprotein (VSVG) envelope to enhance the tropism of these mutant viruses. In addition to gag/pol, the mutant viruses lacked one of the following, env, nef, rev, vif, vpr, or vpu. In addition, we generated single gene expressing pseudotyped viruses to complement the scanning mutation approach of our viral parental construct. Murine podocytes were then infected with one of the viral constructs either lacking or expressing the various HIV-1 genes. We found that HIV-1 nef was necessary and sufficient for proliferation of podocytes and down-regulation of synaptopodin and CALLA. These data suggest that Nef induces many of the changes we observe in HIV transgenic model and, as a result, this now defines the pathway for exploration of host responses to HIV-1 infection.
 ...
PMID:Critical role for Nef in HIV-1-induced podocyte dedifferentiation. 1453 2