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The Keio Journal of Medicine Dec 1996Acquired Immunodeficiency Syndrome (AIDS) was first described to occur in children in 1983. With experience of increasing number of cases of AIDS, pathologic lesions in... (Review)
Review
OVERVIEW
Acquired Immunodeficiency Syndrome (AIDS) was first described to occur in children in 1983. With experience of increasing number of cases of AIDS, pathologic lesions in various organs and tissues such as lungs, brain, G.I. tract, heart, blood vessels, lymph nodes, spleen, bone marrow, etc. became evident in autopsy and biopsy specimens. These pathologic lesions were classified into four groups based on known or suspected pathogenesis: 1) Primary lesions due to Human Immunodeficiency (HIV) infection itself (lymph nodes, brain, etc) 2) associated lesions related to direct or indirect sequelae of HIV infection (Opportunistic infections, PLH/LIP complex, etc) 3) lesions of undetermined pathogenesis, (cardiomyopathy, arteriopathy, thrombocytopenia, nephropathy, etc) 4) lesions of multifactorial pathogenesis (villous atrophy of intestine, thymic lesions, etc).
UPDATE
In recent years the emphasis of pathologic study is on the reactive and neoplastic proliferative disorders. These disorders include nodal and extranodal lymphoproliferative lesions (such as myoepithelial sialadenitis, malignant lymphomas, etc), smooth muscle tumors (SMTs), Kaposi's sarcoma, Human Papilloma virus associated genital lesions and miscellaneous tumors. In a recent study, it has been shown that Epstein-Barr virus (EBV) may be related to the pathogenesis of SMTs. The most recently recognized lymphoproliferative lesions include those of mucosa associated lymphoid tissue (MALT) of salivary glands, lungs and tonsils. The MALT lymphomas in children with AIDS are responsive to therapy and tend to take an indolent clinical course. Therefore recognition of MALT lymphomas as a distinctive lesion in pediatric AIDS is of practical importance. In this view of increasing incidence of HIV and HPV infections in adolescent females seen in certain countries attention should also be focused on early detection of HPV related genital lesions so that their possible progression to intraepithelial and invasive cervical carcinoma can be prevented.
Topics: Acquired Immunodeficiency Syndrome; Arteries; Child; Female; Humans; Infant, Newborn; Infectious Disease Transmission, Vertical; Lung; Lymphoid Tissue; Lymphoproliferative Disorders; Maternal-Fetal Exchange; Neoplasms; Pregnancy; Thymus Gland
PubMed: 9023448
DOI: 10.2302/kjm.45.306 -
PloS One 2021HIV-positive persons of African descent are disproportionately affected by chronic kidney disease (CKD). Deterioration to end-stage kidney disease (ESKD) also occurs in...
BACKGROUND
HIV-positive persons of African descent are disproportionately affected by chronic kidney disease (CKD). Deterioration to end-stage kidney disease (ESKD) also occurs in this population at a higher frequency. There remains a lot to learn about the genetic susceptibility to CKD in HIV positive patients, and the pathophysiology of progression to ESKD.
OBJECTIVES
We will conduct an exploratory genotype-phenotype study in HIV-positive persons with CKD in Aminu Kano Teaching Hospital, Nigeria, to determine blood-based differential gene expression biomarkers in different kidney risk groups according to the KDIGO 2012 criteria.
METHODS
We will consecutively screen 150 HIV-positive adults (≥18 years of age) attending the HIV clinic of Aminu Kano Teaching Hospital, Kano, Nigeria, for CKD based on proteinuria and elevation of estimated glomerular filtration rate. Among these, two separate groups of 16 eligible participants each (n = 32) will be selected in the four (4) KDIGO 2012 kidney risk categories. The groups will be matched for age, sex, viral suppression level and antiretroviral (ARV) regimen. In the first group (n = 16), we will determine differential gene expression markers in peripheral blood mononuclear cells using mRNA-sequencing (RNA-Seq). We will validate the differential expression markers in the second group (n = 16) using reverse transcription quantitative polymerase chain reaction (RT-qPCR). Using a systems-based approach, we will construct, visualize and analyze gene-gene interaction networks to determine the potential biological roles of identified differential expression markers based on published literature and publicly available databases.
RESULTS
Our exploratory study will provide valuable information on the potential roles of differential expression biomarkers in the pathophysiology of HIV-associated kidney disease by identifying novel biomarkers in different risk categories of CKD in a sub-Saharan African population. The results of this study will provide the basis for population-based genome-wide association studies to guide future personalized medicine approaches.
CONCLUSION
Validated biomarkers can be potential targets for the development of stage-specific therapeutic interventions, an essential paradigm in precision medicine.
Topics: AIDS-Associated Nephropathy; Africa South of the Sahara; Biomarkers; Black People; Disease Progression; Genetic Association Studies; Genetic Predisposition to Disease; Glomerular Filtration Rate; Humans; Leukocytes, Mononuclear; Polymorphism, Single Nucleotide; RNA-Seq
PubMed: 33822824
DOI: 10.1371/journal.pone.0249567 -
Cellular Signalling Mar 2012AT(1)R has been reported to play an important role in the progression of HIV-associated nephropathy (HIVAN); however, the effect of AT(2)R has not been studied. Age and...
AT(1)R has been reported to play an important role in the progression of HIV-associated nephropathy (HIVAN); however, the effect of AT(2)R has not been studied. Age and sex matched control (FVB/N) and Tg26 mice aged 4, 8, and 16weeks were studied for renal tissue expression of AT(1)R and AT(2)R (Protocol A). Renal tissue mRNA expression of AT(2)R was lower in Tg26 mice when compared with control mice. In Protocol B, Tg26 mice were treated with either saline, telmisartan (TEL, AT(1) blocker), PD123319 (PD, AT(2)R blocker), or TEL+PD for two weeks. TEL-receiving Tg26 (TRTg) displayed less advanced glomerular and tubular lesions when compared with saline-receiving Tg26 (SRTg). TRTgs displayed enhanced renal tissue AT(2)R expression when compared to SRTgs. Diminution of renal tissue AT(2)R expression was associated with advanced renal lesions in SRTgs; whereas, upregulation of AT(2)R expression in TRTgs was associated with attenuated renal lesions. PD-receiving Tg26 mice (PDRTg) did not show any alteration in the course of HIVAN; whereas, PD+TEL-receiving Tg26 (PD-TRTg) showed worsening of renal lesions when compared to TRTgs. Interestingly, plasma as well as renal tissues of Tg26 mice displayed several fold higher concentration of Ang III, a ligand of AT(2)R.
Topics: AIDS-Associated Nephropathy; Angiotensin II Type 1 Receptor Blockers; Angiotensin II Type 2 Receptor Blockers; Animals; Benzimidazoles; Benzoates; Humans; Imidazoles; Kidney Glomerulus; Mice; Mice, Transgenic; Pyridines; Receptor, Angiotensin, Type 1; Receptor, Angiotensin, Type 2; Telmisartan
PubMed: 22108089
DOI: 10.1016/j.cellsig.2011.11.007 -
Kidney International Sep 1999
Review
Topics: AIDS-Associated Nephropathy; Adult; Anti-HIV Agents; Ethnicity; HIV-1; Humans; Kidney; Male; Renal Dialysis; Risk Factors; United States
PubMed: 10469389
DOI: 10.1046/j.1523-1755.1999.00748.x -
Gerontology 2018Ever since the introduction of highly active antiretroviral therapy (ART) in 1995, HIV infection has been linked to "metabolic" complications (insulin resistance,... (Review)
Review
Ever since the introduction of highly active antiretroviral therapy (ART) in 1995, HIV infection has been linked to "metabolic" complications (insulin resistance, dyslipidemia, osteoporosis, and others). Studies suggested increased rates of myocardial infarction, renal insufficiency, neurocognitive dysfunction, and fractures in HIV-postitive patients. Even long-term suppression of HIV seemed to be accompanied by an excess of deleterious inflammation that could promote these complications. The aims of this viewpoint paper are to summarize recent data and to examine the possibility that the problem of aging-related morbidity in HIV might not be as dramatic as previously believed.
Topics: AIDS Dementia Complex; AIDS-Associated Nephropathy; Adult; Aged; Aging; Antiretroviral Therapy, Highly Active; Atherosclerosis; Body Composition; Cardiovascular Diseases; Drug Interactions; Fractures, Bone; Frailty; HIV Infections; Humans; Life Expectancy; Male; Metabolic Diseases; Middle Aged; Risk Factors; Telomere Homeostasis
PubMed: 29909411
DOI: 10.1159/000489172 -
Advances in Chronic Kidney Disease Jan 2010HIV-associated nephropathy (HIVAN) is a leading cause of ESRD in African Americans. The HIV-1 virus infects podocytes, cells integral to formation of the glomerular... (Review)
Review
HIV-associated nephropathy (HIVAN) is a leading cause of ESRD in African Americans. The HIV-1 virus infects podocytes, cells integral to formation of the glomerular filtration barrier, often leading to focal segmental glomerulosclerosis. HIVAN is typically a complication of late-stage HIV infection, associated with low CD4 cell counts and elevated serum HIV RNA levels. Highly active antiretroviral therapy is partially protective and has altered the natural history of HIV-associated kidney disease. Nonetheless, HIVAN remains an important public health concern among HIV-infected African Americans. 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. Therefore, we postulate that additional environmental exposures and/or inherited factors are necessary to initiate human HIVAN. Gene-environment interactions have also been proposed as necessary for the initiation of HIVAN in murine models. It is important that these novel risk factors be identified because prevention of environmental exposures and targeting of additional gene products may reduce the risk for HIVAN, even among those harboring 2 risk alleles in MYH9.
Topics: AIDS-Associated Nephropathy; Black or African American; Animals; Disease Models, Animal; Environment; Genetic Predisposition to Disease; Humans; Molecular Motor Proteins; Myosin Heavy Chains; Risk Factors
PubMed: 20005488
DOI: 10.1053/j.ackd.2009.08.002 -
Muscle & Nerve Jan 2015Distal symmetric polyneuropathy (DSP) is common in HIV and is associated with autonomic impairment. However tools to measure HIV-DSP do not include autonomic indices. We...
INTRODUCTION
Distal symmetric polyneuropathy (DSP) is common in HIV and is associated with autonomic impairment. However tools to measure HIV-DSP do not include autonomic indices. We sought to optimize the Total Neuropathy Score (TNS) and the Composite Autonomic Severity Score (CASS) for use in HIV.
METHODS
HIV-infected adults (n = 102) underwent neurologic examination, quantitative sensory testing (QST), nerve conduction studies, and autonomic testing. Modifications of the TNS and CASS were assessed for validity based on correlation with the original measure and internal consistency.
RESULTS
The TNS version commonly used in HIV-DSP is valid, but it is improved by elimination of QST and addition of autonomic indices. A modified version of the CASS (M-CASS) which was designed for sensitivity to milder impairment was also valid.
CONCLUSIONS
A modified TNS that excludes QST and includes autonomic indices is optimal for HIV-DSP. The M-CASS is a valid measure of autonomic impairment in HIV.
Topics: AIDS-Associated Nephropathy; Adult; Female; Humans; Male; Middle Aged; Neural Conduction; Neurologic Examination; Pain; Peripheral Nerves; Severity of Illness Index
PubMed: 24809943
DOI: 10.1002/mus.24282 -
Journal of the American Society of... Nov 2011Trypanolytic variants in APOL1, which encodes apolipoprotein L1, associate with kidney disease in African Americans, but whether APOL1-associated glomerular disease has...
Trypanolytic variants in APOL1, which encodes apolipoprotein L1, associate with kidney disease in African Americans, but whether APOL1-associated glomerular disease has a distinct clinical phenotype is unknown. Here we determined APOL1 genotypes for 271 African American cases, 168 European American cases, and 939 control subjects. In a recessive model, APOL1 variants conferred seventeenfold higher odds (95% CI 11 to 26) for focal segmental glomerulosclerosis (FSGS) and twenty-nine-fold higher odds (95% CI 13 to 68) for HIV-associated nephropathy (HIVAN). FSGS associated with two APOL1 risk alleles associated with earlier age of onset (P = 0.01) and faster progression to ESRD (P < 0.01) but similar sensitivity to steroids compared with other subjects. Individuals with two APOL1 risk alleles have an estimated 4% lifetime risk for developing FSGS, and untreated HIV-infected individuals have a 50% risk for developing HIVAN. The effect of carrying two APOL1 risk alleles explains 18% of FSGS and 35% of HIVAN; alternatively, eliminating this effect would reduce FSGS and HIVAN by 67%. A survey of world populations indicated that the APOL1 kidney risk alleles are present only on African chromosomes. In summary, African Americans carrying two APOL1 risk alleles have a greatly increased risk for glomerular disease, and APOL1-associated FSGS occurs earlier and progresses to ESRD more rapidly. These data add to the evidence base required to determine whether genetic testing for APOL1 has a use in clinical practice.
Topics: AIDS-Associated Nephropathy; Adult; Black or African American; Age of Onset; Apolipoprotein L1; Apolipoproteins; Case-Control Studies; Disease Progression; Genetic Variation; Genotype; Glomerulosclerosis, Focal Segmental; HapMap Project; Human Genome Project; Humans; Kaplan-Meier Estimate; Lipoproteins, HDL; Middle Aged; Risk Factors; United States; White People; Young Adult
PubMed: 21997394
DOI: 10.1681/ASN.2011040388 -
Pediatric Nephrology (Berlin, Germany) Nov 2009Childhood human immunodeficiency virus-associated nephropathy (HIVAN) is defined by the presence of proteinuria associated with mesangial hyperplasia and/or global-focal... (Review)
Review
Childhood human immunodeficiency virus-associated nephropathy (HIVAN) is defined by the presence of proteinuria associated with mesangial hyperplasia and/or global-focal segmental glomerulosclerosis, in combination with the microcystic transformation of renal tubules. This review discusses the pathogenesis of childhood HIVAN and explores how the current pathological paradigm for HIVAN in adults can be applied to children. The Human Immunodeficiency Virus-1 (HIV-1) induces renal epithelial injury in African American children with a genetic susceptibility to develop HIVAN. The mechanism is not well understood, since renal epithelial cells harvested from children with HIVAN do not appear to be productively infected. Children with HIVAN show a renal up-regulation of heparan sulphate proteoglycans and a recruitment of circulating heparin-binding growth factors, chemokines, and mononuclear cells. Macrophages appear to establish a renal HIV-reservoir and transfer viral particles to renal epithelial cells. All of these changes seem to trigger an aberrant and persistent renal epithelial proliferative response. The paradigm that viral products produced by infected renal epithelial cells per se induce the proliferation of these cells is not supported by data available in children with HIVAN. More research is needed to elucidate how HIV-1 induces renal epithelial injury and proliferation in HIV-infected children.
Topics: AIDS-Associated Nephropathy; Child; Epithelial Cells; HIV Infections; HIV-1; Humans; Kidney Diseases; Kidney Tubules; Models, Biological
PubMed: 19288142
DOI: 10.1007/s00467-009-1155-4 -
Computational and Structural... 2023Diabetic nephropathy (DN) is one of the most established microvascular complications of diabetes and a key cause of end-stage renal disease. It is well established that...
Diabetic nephropathy (DN) is one of the most established microvascular complications of diabetes and a key cause of end-stage renal disease. It is well established that gene susceptibility to DN plays a critical role in disease pathophysiology. Therefore, many genetic studies have been performed to categorize candidate genes in prominent diabetic cohorts, aiming to investigate DN pathogenesis and etiology. In this study, we performed a meta-analysis on the expression profiles of GSE1009, GSE30122, GSE96804, GSE99340, GSE104948, GSE104954, and GSE111154 to identify critical transcriptional factors associated with DN progression. The analysis was conducted for all individual datasets for each kidney tissue (glomerulus, tubules, and kidney cortex). We identified distinct clusters of susceptibility genes that were dysregulated in a renal compartment-specific pattern. Further, we recognized a small but a closely connected set of these susceptibility genes enriched for podocyte differentiation, several of which were characterized as genes encoding critical transcriptional factors (TFs) involved in DN development and podocyte function. To validate the role of identified TFs in DN progression, we functionally validated the three main TFs (DACH1, LMX1B, and WT1) identified through differential gene expression and network analysis using the hyperglycemic zebrafish model. We report that hyperglycemia-induced altered gene expression of the key TF genes leads to morphological abnormalities in zebrafish glomeruli, pronephric tubules, proximal and distal ducts. This study demonstrated that altered expression of these TF genes could be associated with hyperglycemia-induced nephropathy and, thus, aids in understanding the molecular drivers, essential genes, and pathways that trigger DN initiation and development.
PubMed: 36659918
DOI: 10.1016/j.csbj.2022.12.054