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Query: UMLS:C0033687 (proteinuria)
 24,015 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Patients infected with human immunodeficiency virus type 1 (HIV-1) develop a renal syndrome characterized by proteinuria, renal failure, and focal segmental glomerulosclerosis. By using a noninfectious HIV-1 DNA construct lacking the gag and pol genes, three transgenic mouse lines have been generated that develop a syndrome remarkably similar to the human disease. In the present study, we have characterized in detail one of these lines, Tg26. In Tg26 mice, proteinuria was detectable at approximately 24 days of age, followed by severe nephrotic syndrome and rapid progression to end-stage renal failure. Renal histology showed focal segmental glomerulosclerosis and microcystic tubular dilatation. Indirect immunofluorescence studies demonstrated increased accumulation of the basement membrane components laminin, collagen type IV, and heparan sulfate proteoglycan. The viral protein Rev was present in sclerotic glomeruli. Northern blot analysis of total renal RNA showed expression of viral genes prior to the appearance of histologic renal disease, with greatly diminished viral gene expression late in the disease course. Kidneys from transgenic mice expressed increased steady-state levels of collagen alpha 1(IV) mRNA when glomerulosclerosis was present. We conclude that the presence of HIV-1 genes is associated with progressive renal dysfunction and glomerulosclerosis in transgenic mice.
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PMID:Progressive glomerulosclerosis and enhanced renal accumulation of basement membrane components in mice transgenic for human immunodeficiency virus type 1 genes. 154 49

Renal alterations characterized morphologically by glomerular and tubulo-interstitial lesions and clinically by a heavy proteinuria and sometimes by renal failure are frequent in feline immunodeficiency virus (FIV) infected cats. To investigate the possible role of local FIV replication in the genesis of this renal damage, renal tissues of 15 consecutive naturally infected and five non-infected cats were examined for traces of the virus by immunohistochemistry, using a monoclonal anti-p24 antibody in a streptavidin-biotin peroxidase labeled system, cultivation and polymerase chain reaction (PCR). Tubular epithelial cells as well as scattered interstitial inflammatory and glomerular cells were positive for p24 antigen in 13 cats. Viral isolation was successful in seven cats, and FIV gag DNA and RNA sequences were detected in 14 and five cats, respectively. Control cats were constantly negative. Although not conclusive, these results suggest that a direct role of FIV in the induction of the renal damage observed in infected animals is possible.
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PMID:Renal involvement in feline immunodeficiency virus infection: p24 antigen detection, virus isolation and PCR analysis. 761 53

Although focal glomerulosclerosis is the most common renal disease, other proliferative glomerulonephritides are encountered in HIV-infected patients. We studied four HIV-infected patients with renal insufficiency, proteinuria, and proliferative glomerulonephritis, consistent with immune-mediated disease, to investigate the role of the virus and immune complexes in the pathogenesis of the nephropathy. Circulating immune complexes (CICs) and HIV-reactive antibodies were measured and characterized in each patient. Renal biopsy tissue was acid eluted, and the eluate analyzed. DNA extracted from biopsies was subjected to the polymerase chain reaction (PCR) to detect HIV genome. CICs were detected in each patient: an IgA-p24 HIV antigen complex and an IgG antibody-gp 120 HIV antigen complex in two patients; two patients had an IgG-p24 HIV antigen complex. Identical complexes were eluted from renal tissue in the first three patients; p24 HIV antigen, and complement from the fourth. The eluted antibodies reacted with the HIV antigens from the isolated CICs. Direct immunofluorescence for viral antigen in the eluted glomerular tissue revealed HIV antigens; PCR confirmed the presence of gag genome in all four biopsies. We conclude both circulating and in-situ HIV antigen-specific immune complexes may be associated with glomerulonephritis in HIV infected patients. Viral incorporation into renal tissue may be important in the pathogenesis of HIV-associated renal disease.
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PMID:HIV-associated immune-mediated renal disease. 830 34

Focal glomerulosclerosis (FGS) has been considered as HIV-associated nephropathy, a specific renal complication of infection. To determine whether renal disease in HIV infected patients has one highly prevalent pathologic expression, and whether renal parenchymal viral genomic incorporation affects pathologic outcome, we reviewed renal biopsies performed at our center. Twenty-eight HIV infected patients with nephrotic range proteinuria underwent renal biopsy for diagnosis of renal disease: 85.7% led homosexual or bisexual lifestyles; 10.7% admitted to intravenous drug use; and 85.7% were Black. Only 53.6% had FGS; 28.6% had glomerulonephritis. Two patients had diabetic renal disease; 93.3% of patients with FGS and 87.5% of patients with glomerulonephritis were Black. Paraffin slides of twenty-two of the patients' renal biopsies were evaluated by polymerase chain reaction (PCR) for the presence of HIV DNA, using primers and probes to the gag gene, detected by liquid hybridization and polyacrylamide gel electrophoresis. Twenty-one of the twenty-two evaluated tissue specimens showed the presence of HIV DNA. Microdissection studies of glomeruli, tubules, interstitial cells and infiltrating inflammatory cells showed the presence of HIV genome in all but interstitial cells. HIV infected patients without renal disease also had positive PCR evaluations of microdissected tissue, while non-infected patients were all negative. We conclude that although focal glomerulosclerosis is the most common renal pathologic lesion in patients with HIV infection and nephrotic range proteinuria, glomerulonephritis is a relatively frequent finding. HIV genome is present in renal tissue in HIV infected subjects with nephrotic range proteinuria, but is also found in HIV infected subjects without nephropathy.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Viral DNA in microdissected renal biopsy tissue from HIV infected patients with nephrotic syndrome. 831 49

HIV-associated nephropathy is a clinicopathologic entity that includes proteinuria, focal segmental glomerulosclerosis often of the collapsing variant, and microcystic tubulointerstitial disease. Increasing evidence supports a role for HIV-1 infection of renal epithelium in the pathogenesis of HIV-associated nephropathy. Using in situ hybridization, we previously demonstrated HIV-1 gag and nef mRNA in renal epithelial cells of patients with HIV-associated nephropathy. Here, to investigate whether renal epithelial cells were productively infected by HIV-1, we examined renal tissue for the presence of HIV-1 DNA and mRNA by in situ hybridization and PCR, and we molecularly characterized the HIV-1 quasispecies in the renal compartment. Infected renal epithelial cells were removed by laser-capture microdissection from biopsies of two patients, DNA was extracted, and HIV-1 V3-loop or gp120-envelope sequences were amplified from individually dissected cells by nested PCR. Phylogenetic analysis of kidney-derived sequences as well as corresponding sequences from peripheral blood mononuclear cells of the same patients revealed evidence of tissue-specific viral evolution. In phylogenetic trees constructed from V3 and gp120 sequences, kidney-derived sequences formed tissue-specific subclusters within the radiation of blood mononuclear cell-derived viral sequences from both patients. These data, along with the detection of HIV-1-specific proviral DNA and mRNA in tubular epithelium cells, argue strongly for localized replication of HIV-1 in the kidney and the existence of a renal viral reservoir.
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PMID:Replication and compartmentalization of HIV-1 in kidney epithelium of patients with HIV-associated nephropathy. 1198 99

Clinical and morphologic features of human immunodeficiency virus (HIV)-associated nephropathy (HIVAN), such as proteinuria, sclerosing glomerulopathy, tubular degeneration, and interstitial disease, have been modeled in mice bearing an HIV proviral transgene rendered noninfectious through a deletion in gag/pol. Exploring the genetic basis of HIVAN, HIV transgenic mice bearing mutations in either or both of the accessory genes nef and vpr were created. Proteinuria and focal glomerulosclerosis (FGS) only developed in mice with an intact vpr gene. Transgenic mice bearing a simplified proviral DNA (encoding only Tat and Vpr) developed renal disease characterized by FGS in which Vpr protein was localized to glomerular and tubular epithelia by immunohistochemistry. The dual transgenic progeny of HIV[Tat/Vpr] mice bred to HIV[DeltaVpr] proviral transgenic mice displayed a more severe nephropathy with no apparent increase in Vpr expression, implying that multiple viral genes contribute to HIVAN. However, the unique contribution of macrophage-specific Vpr expression in the development of glomerular disease was underscored by the induction of FGS in multiple murine lines bearing a c-fms/vpr transgene.
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PMID:Focal glomerulosclerosis in proviral and c-fms transgenic mice links Vpr expression to HIV-associated nephropathy. 1506 18

Since 1984 reports of renal involvement in AIDS patients have been presented in the literature. Different forms of renal disease were noted in the AIDS population including those related to systemic and local renal infections, tubulointerstitial disease, renal involvement by neoplasm and glomerular disease including collapsing glomerulopathy (CG). HIV-associated nephropathy (HIVAN) has been demonstrated to be more severe in the black population. HIVAN is the most common cause of renal failure in HIV-1-seropositive patients. The term HIVAN is reserved for the typical histopathological form of focal and segmental glomerulosclerosis (FSGS) characterized by the findings of coexistent glomerular and severe tubulointerstitial disease. In both humans and the murine model, glomerular lesions include FSGS, glomerular collapse and podocyte hyperplasia. The tubulointerstitial damage as well as the glomerular collapse can also be seen in non-HIV primary collapsing GN, raising the question of common mechanisms to HIV and other non-identified viral agents related to the development of the disease. Although controversial, increasing evidence supports a direct effect of the virus on renal cells either as a result of exposure to viral proteins or direct renal parenchyma infection. The use of a HIV-1 transgenic mouse model has demonstrated a direct etiologic link between HIV-1 expression in kidney and the development of HIVAN with unique viral-host interactions, which depend at the same time on stimulating features of the virus and the individual nature of the host response. The infection of renal cells by HIV-1 could be detected by reverse transcription-polymerase chain reaction (RT-PCR) of gag RNA at a low level. Some studies using an HIV-1 transgenic mouse model have demonstrated that expression of HIV- 1 in the kidney is required for the development of HIVAN. The final common pathway in the development of HIV-associated nephropathy is likely to involve alterations in the patterns of gene expression of renal parenchyma cells by cytokines and growth factors, leading to interstitial fibrosis and enhanced glomerular matrix synthesis. The nature of the host response to viral infection is critical to the development of nephropathy.HLA-linked responses particular to a subset of blacks may explain some of the epidemiologic features of HIVAN. There may also be biological heterogeneity in the strains of HIV-1 that could account for a particular renotropic strain. HIV strains from different parts of the world may vary by as much as 15% at the level of nucleotide sequence. The infectivity of human immunodeficiency virus (HIV-1) in human glomerular cells has been evaluated by exposing homogeneous cultures of human glomerular capillary endothelial, mesangial and epithelial cells to HIV in vitro. The mechanism of access of HIV into glomerular endothelial and mesangial cells is unknown up to now; HIV is generally infectious for cells expressing the CD4 antigen in their cell membrane. Other modes of HIV entry into cells independent of the CD4 receptor are possible through mechanisms involving Fc-receptors or coinfection with other enveloped viruses such as HTLV-l. Our understanding of the pathogenesis of HIVAN has been aided by the development of a transgenic model. The curious fact that only 3 of 8 founded transgenic lines developed nephropathy emphasizes that the expression of viral gene products per se is not sufficient to produce nephropathy. Human renal epithelium does not express CD4 receptors and in vitro attempts to infect glomerular epithelial cells using laboratory strains of HIV-1 have proven fruitless. The striking morphologic and phenotypic similarities between HIVAN and collapsing idiopathic FSGS raise the question whether the altered podocyte gene expression in collapsing idiopathic FSGS may also be due to a viral infection. This hypothesis is further supported by de novo occurrence of collapsing idiopathic FSGS in immunosuppressed renal transplantation patients and by epidemiologic data. In conclusion, there are likely to be common mechanisms in the pathogenesis for collapsing idiopathic glomerulosclerosis and HIVAN. A primary injury of the podocyte leading to dysregulation of the cellular phenotype appears to mediate the glomerular tuft collapse in both conditions. Primary collapsing glomerulopathy recurs post-transplantation, raising the possibility of circulating factors implicated in the pathogenesis of visceral epithelial cell damage in steroid-resistant minimal change disease or recurrent FSGS. Recurrence of CG can occur hours after transplantation, suggesting that the plasma of CG patients contains one or more factors capable of inducing proteinuria due to the damage of the podocyte that results in the increase in glomerular permeability. In a rat model of CG developed by our group, the injection of serum from CG patients resulted in proteinuria, glomerular tuft retraction and podocyte damage at the ultrastructural level (visceral epithelial cell foot-process effacement). No ultrastructural or light microscopy abnormalities were seen in rats injected with serum from non-collapsing FSGS or healthy subjects. Based on the experience of our group, circulating factors play a dominant role in the pathogenesis of idiopathic CG.
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PMID:HIV-associated nephropathy: experimental models. 2125 26