Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Collapsing glomerulopathy (CG), a variant of idiopathic focal segmental glomerulosclerosis (FSGS), can occur in both human immunodeficiency virus (HIV)-positive and HIV-negative patients. Idiopathic membranous glomerulonephritis (MGN) has been reported to coexist with FSGS, but rarely with CG. We report 3 HIV-negative patients (2 men, 1 woman) who developed nephrotic syndrome secondary to MGN complicated by CG, with relatively rapid disease progression despite aggressive therapy.
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PMID:Collapsing glomerulopathy coexisting with membranous glomerulonephritis in native kidney biopsies: a report of 3 HIV-negative patients. 1295 90

Idiopathic collapsing glomerulopathy is an aggressive variant of focal segmental glomerulosclerosis (FSGS) seen primarily in adults. Its etiology is unknown. Nearly identical pathology is seen in association with nephrotic syndrome in human immunodeficiency virus type 1 (HIV-1)-infected patients, raising the possibility that viral infection plays a role in pathogenesis. This is supported by the recent discovery of parvovirus B19 DNA in some cases of idiopathic collapsing glomerulopathy. We report a case of collapsing glomerulopathy in a 16-year-old girl who presented with steroid-resistant nephrotic syndrome and pulmonary tuberculosis. In the absence of the usual associations (adult age group, African-American race, or history of intravenous drug abuse), infection is the sole known risk factor in this case. This lends support to the hypothesis that immune dysregulation due to infection per se, rather than infection by specific viral agents, may lead to collapsing glomerulopathy in susceptible individuals.
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PMID:Collapsing glomerulopathy in a 16-year-old girl with pulmonary tuberculosis: the role of systemic inflammatory mediators. 1517 56

The proliferative response of podocytes to injury determines the histological phenotype. Moreover, an apparent lack of podocyte proliferation may underlie the development of glomerulosclerosis. Podocyte proliferation is closely linked with its state of differentiation. However, the mechanisms regulating these processes are not fully elucidated. Because D-type cyclins have been shown to be important in the regulation of proliferation and differentiation, we examined their expression in podocytes in vitro and in vivo. The glomerular expression of cyclins D1 and D3 was examined in vitro in cultured immortalized podocytes by immunostaining and Western blot analysis, and in embryonic mice and rats, the passive Heymann nephritis model of experimental membranous nephropathy in rats, and human immunodeficiency virus (HIV)-transgenic mice. Kidneys from cyclin D1 knockout mice were also examined. Cyclin D1 was abundant in cultured proliferating podocytes, but not in quiescent differentiated podocytes. In contrast, cyclin D3 was abundant in differentiated, but not proliferating podocytes. Cyclin D1 was expressed in embryonic mouse and rat glomeruli during the S- and comma-shaped stages, and was absent in podocytes at the capillary loop stage and in mature rodent glomeruli. Cyclin D1 protein increased after injury in passive Heymann nephritis rats and in HIV-transgenic mice. Cyclin D3 was constitutively and specifically expressed in podocytes in normal rodent glomeruli, and decreases during dedifferentiation and proliferation in HIV-transgenic mice. Kidneys from cyclin D1-/- mice were normal with the podocytes expressing specific differentiation markers. Cyclin D1 is not necessary for the terminal differentiation of podocytes, and expression coincides with cell-cycle entry. In contrast, cyclin D3 expression coincides with podocyte differentiation and quiescence.
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PMID:Differential expression of d-type cyclins in podocytes in vitro and in vivo. 1503 29

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

Toxic nephropathy is an important cause of reversible renal injury. This article focuses on the nephrotoxicity of several new therapeutic compounds. Selective cyclooxygenase-2 inhibitor is associated with sodium retention, hypertension, ankle edema, and acute renal failure. The incidence of renal complication is similar to conventional nonsteroidal anti-inflammatory drugs. Bisphosphonates, especially when used in high dose for prolonged duration, can cause toxic acute tubular necrosis and renal failure. Pamidronate is also associated with a specific form of collapsing focal segmental glomerulosclerosis similar to one found in patients with human immunodeficiency virus (HIV) infection. Acyclic nucleoside phosphonate, a new group of antiviral agents, can cause Fanconi-like syndrome and progressive renal impairment. On the other hand, indinavir, a potent protease inhibitor for the treatment of HIV infection, can cause crystalluria, renal stone, acute tubular obstruction and chronic interstitial nephritis. Intravenous immune globulin and hydroxyethyl starch, a new plasma expander, are associated with acute renal failure with characteristic renal histology known as osmotic nephrosis. In short, physicians should be cautious about possible renal toxicity during the use of any new therapeutic agents.
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PMID:Nephrotoxicity related to new therapeutic compounds. 1595 51

A 10-year-old Turkish boy with consanguineous parents was presented with a disproportionately short stature and a nephrotic syndrome. The mild form of Schimke's immuno-osseous dysplasia was diagnosed as the common cause. This rare, autosomal recessive osteochondrodysplasia is characterised by spondyloepiphyseal dysplasia, facial dysmorphism, T-cell immunodeficiency and progressive renal failure due to focal segmental glomerulosclerosis. In Schimke's immuno-osseous dysplasia, a severe early-onset form and a milder later-onset form can be distinguished on the basis of the clinical course. The patient was treated by fluid and salt restriction, enalapril and later also losartan, which led to a decrease in the proteinuria and an increase in serum albumin concentration. Two years later, the renal function was still normal.
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PMID:[Schimke's immuno-osseous dysplasia as an explanation for the rare combination of disproportionately short stature and the nephrotic syndrome]. 1622 78

Autosomal-recessive Schimke immuno-osseous dysplasia (SIOD) characterized by spondyloepiphyseal dysplasia, focal-segmental glomerulosclerosis (FSGS), T-cell immunodeficiency and facial dysmorphism is caused by defects in the SMARCAL1 gene. The gene product is involved in the transcriptional regulation of other genes. A 12-year-old boy of consanginous Turkish descent developed disproportionate short stature from spondyloepiphyseal dysplasia at the age of 6 and nephrotic syndrome at the age of 10 years. Renal biopsy revealed FSGS, the kidney function was normal, T-lymphocytes were diminished without infectious complications, and he has had no cerebral ischemia. Analysis of the patient's SMARCAL1 gene revealed a novel homozygous C1798T transition leading to a R561C substitution. The parents and two healthy sisters were found to be heterozygous. A younger brother, who is also homozygous for the mutation, is clinically asymptomatic and has no proteinuria at the age of 18 months. Still, his CD4 cells are diminished. For SMARCAL1 mutations a clear genotype-phenotype correlation has been reported: severe SIOD with in utero or early-childhood onset leading to end-stage renal disease within a few years is caused by nonsense, frame shift or splice mutations. Many patients die from infections and cerebrovascular insults during childhood. Mild SIOD manifests later and progresses more slowly without infectious or cerebral vascular complications--the underlying defect being missense mutations in all three patients reported so far. The novel R561C missense mutation in our patient with mild SIOD is additional evidence for the genotype-phenotype correlation reported for SMARCAL1 mutations.
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PMID:R561C missense mutation in the SMARCAL1 gene associated with mild Schimke immuno-osseous dysplasia. 1623 66

Renal disease is becoming an increasingly prevalent entity in human immunodeficiency virus (HIV)-infected patients; it occurs in a variety of clinical settings and is associated with histopathological changes. HIV-related renal impairment can present as acute or chronic kidney disease; it can be caused directly or indirectly by HIV and/or by drug-related effects that are directly nephrotoxic or lead to changes in renal function by inducing metabolic vaculopathy and renal damage. Acute renal failure is frequently caused by the toxic effects of antiretroviral therapy or nephrotoxic antimicrobial substances used in the treatment of opportunistic infections. Chronic renal disease can be caused by multiple pathophysiological mechanisms, leading to HIV-associated nephropathy, a form of collapsing focal glomerulosclerosis, thrombotic microangiopathy, and various forms of immune complex glomerulonephritis. The increase in life expectancy and alteration of lipid metabolism due to receipt of highly active antiretroviral therapy are expected to result in an increased prevalence of diabetes and hypertension and, thus, to secondary diabetic and hypertensive renal damage. Antiretroviral agents, such as indinavir and tenofovir, have been associated with nephrotoxic drug effects that have been shown to be reversible in most cases. In this article, we review the current knowledge about acute and chronic HIV-associated renal disease, metabolic alterations and related nephropathies, and toxic drug effects of combination antiretroviral pharmacotherapy.
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PMID:HIV-associated renal diseases and highly active antiretroviral therapy-induced nephropathy. 1661 64

Human immunodeficiency virus (HIV)-associated nephropathy (HIVAN) is an important cause of renal failure in those of African origin. A number of other kidney diseases occur in HIV-positive patients. We conducted a retrospective review of renal biopsies in HIV-positive Black African patients to determine the prevalence of both 'classic HIVAN' and non-HIVAN pathologies in this group. Clinical and laboratory data from HIV-positive patients who underwent renal biopsy from 1st January 2003 to 31st December 2004 were collected. Similar information on HIV-negative patients biopsied during the same period was also recorded by way of comparison to try and assess the influence of the virus on renal histologic patterns. HIV-positive group - 99 biopsies were suitable for study. The main histologic categories were 'classic HIVAN' (27%) and HIV immune complex kidney disease ('HIVICK') (21%). The subepithelial immune deposits in 'HIVICK' induced a newly described 'ball-in-cup' basement membrane reaction. Other glomerulonephritides included membranous, post-infectious disease, mesangial hyperplasia, and immunoglobulin A nephropathy. Overlapping clinical presentations prevented pre-biopsy histologic predictions. HIV-negative group - There were no examples of collapsing focal segmental glomerulosclerosis or nonspecific immune complex disease, but increased numbers of minimal change and membranoproliferative disease. 'Classic HIVAN' accounted for less than a third of the nephropathies occurring in HIV-positive Black South Africans. 'HIVICK' is another important cause of chronic kidney disease in this group. Future research is needed into the earlier detection and treatment of these diseases, which have a high mortality in our context.
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PMID:HIV-related nephropathy: a South African perspective. 2107 53

Alpha(v)beta8 integrin expression is restricted primarily to kidney, brain, and placenta. Targeted alpha(v) or beta8 deletion is embryonic lethal due to defective placenta and brain angiogenesis, precluding investigation of kidney alpha(v)beta8 function. We find that kidney beta8 is localized to glomerular mesangial cells, and expression is decreased in mouse models of glomerulosclerosis, suggesting that beta8 regulates normal mesangial cell differentiation. To interrogate beta8 signaling pathways, yeast two-hybrid and co-precipitation studies demonstrated beta8 interaction with Rho guanine nucleotide dissociation inhibitor-1 (GDI). Selective beta8 stimulation enhanced beta8-GDI interaction as well as Rac1 (but not RhoA) activation and lamellipodia formation. Mesangial cells from itgb8-/- mice backcrossed to a genetic background that permitted survival, or gdi-/- mice, which develop glomerulosclerosis, demonstrated RhoA (but not Rac1) activity and alpha-smooth muscle actin assembly, which characterizes mesangial cell myofibroblast transformation in renal disease. To determine whether Rac1 directly modulates RhoA-associated myofibroblast differentiation, mesangial cells were transduced with inhibitory Rac peptide fused to human immunodeficiency virus-Tat, resulting in enhanced alpha-smooth muscle actin organization. We conclude that the beta8 cytosolic tail in mesangial cells organizes a signaling complex that culminates in Rac1 activation to mediate wild-type differentiation, whereas decreased beta8 activation shifts mesangial cells toward a RhoA-dependent myofibroblast phenotype.
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PMID:Beta8 integrin binds Rho GDP dissociation inhibitor-1 and activates Rac1 to inhibit mesangial cell myofibroblast differentiation. 1669 Jun 20


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