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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 -
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 -
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 -
Kidney International May 2020HIV-associated kidney disease is evolving rapidly. Few North American studies have addressed modern trends and none has applied the 2018 Kidney Disease Improving Global...
HIV-associated kidney disease is evolving rapidly. Few North American studies have addressed modern trends and none has applied the 2018 Kidney Disease Improving Global Outcomes (KDIGO) pathologic classification. Therefore we performed a retrospective clinical-pathologic analysis of all HIV-positive patients with kidney biopsy interpreted at Columbia University from 2010-2018 using the KDIGO classification. The biopsy cohort of 437 HIV-positive patients had median age 53 years, including 66% males, 80% on anti-retroviral therapy, 57% with hypertension, 31% with diabetes, 27% with hepatitis C and 6% with hepatitis B co-infections. Race, known in 308 patients, included 58% black, 25% white and 17% Hispanic. Pathologic diagnoses were surprisingly diverse. Immune complex glomerulonephritis (ICGN) and diabetic nephropathy each outnumbered HIV-associated nephropathy, followed by tenofovir nephrotoxicity, FSGS- not otherwise specified (NOS) and global sclerosis (NOS). HIV-associated nephropathy was the most common disease in patients not on anti-retroviral therapy, and 94% were black. The association of FSGS (NOS) with black race (68%) and anti-retroviral therapy use (77%) suggests some cases may represent attenuated HIV-associated nephropathy. The most common ICGNs were IgA nephropathy and membranous glomerulopathy, both associating with anti-retroviral therapy (over 90%), followed by hepatitis C-associated proliferative ICGN. Among the 16 cases of uncharacterized ICGN lacking identifiable etiology, 69% were not on anti-retroviral therapy, possibly representing true HIV-associated immune complex kidney disease. Dual diseases occurred in 17% of patients, underscoring lesion complexity. Thus, anti-retroviral therapy has shifted the landscape of HIV-associated kidney disease toward diverse ICGN, diabetic nephropathy, and non-collapsing glomerulosclerosis, but has not eradicated HIV-associated nephropathy.
Topics: AIDS-Associated Nephropathy; Biopsy; Female; HIV Infections; Humans; Kidney; Male; Middle Aged; Retrospective Studies
PubMed: 32278618
DOI: 10.1016/j.kint.2020.01.018 -
Disease Models & Mechanisms Oct 2020Modern antiretroviral therapies (ART) have decreased the prevalence of HIV-associated nephropathy (HIVAN). Nonetheless, we continue to see children and adolescents with...
Modern antiretroviral therapies (ART) have decreased the prevalence of HIV-associated nephropathy (HIVAN). Nonetheless, we continue to see children and adolescents with HIVAN all over the world. Furthermore, once HIVAN is established in children, it is difficult to revert its long-term progression, and we need better animal models of childhood HIVAN to test new treatments. To define whether the HIV-1 trans-activator () gene precipitates HIVAN in young mice, and to develop an inducible mouse model of childhood HIVAN, an HIV-Tat gene cloned from a child with HIVAN was used to generate recombinant adenoviral vectors (rAd-). rAd- and control vectors (2×10) were expressed in the kidney of newborn wild-type and HIV-transgenic (Tg) FVB/N mice without significant proteinuria (=5; 8 per group). Mice were sacrificed 7 and 35 days later to assess their renal outcome, the expression of HIV-genes and growth factors, and markers of cell growth and differentiation by RT-qPCR, immunohistochemistry and/or western blots. HIV-Tat induced the expression of HIV-1 genes and heparin-binding growth factors in the kidney of HIV-Tg mice, and precipitated HIVAN in the first month of life. No significant renal changes were detected in wild-type mice infected with rAd- vectors, suggesting that HIV-Tat alone does not induce renal disease. This new mouse model of childhood HIVAN highlights the critical role that HIV-Tat plays in the pathogenesis of HIVAN, and could be used to study the pathogenesis and treatment of HIVAN in children and adolescents.
Topics: AIDS-Associated Nephropathy; Albuminuria; Amino Acid Sequence; Animals; Animals, Newborn; Apoptosis; Cell Dedifferentiation; Cell Proliferation; Child; Disease Models, Animal; Fibroblast Growth Factor 2; HIV-1; Humans; Kidney; Mice, Transgenic; Podocytes; RNA, Messenger; Vascular Endothelial Growth Factor A; beta-Galactosidase; env Gene Products, Human Immunodeficiency Virus; tat Gene Products, Human Immunodeficiency Virus
PubMed: 32917744
DOI: 10.1242/dmm.045641 -
Kidney International Aug 2014The epidemiology of kidney disease in HIV-infected individuals has changed significantly since the introduction of combination antiretroviral therapy (cART) in the mid... (Review)
Review
The epidemiology of kidney disease in HIV-infected individuals has changed significantly since the introduction of combination antiretroviral therapy (cART) in the mid 1990s. HIV-associated nephropathy (HIVAN), an aggressive form of collapsing focal segmental glomerulosclerosis (FSGS) caused by direct HIV infection of the kidney in a genetically susceptible host, emerged early in the HIV epidemic as a leading cause of end-stage renal disease. With the widespread use of cART, HIVAN is increasingly rare in populations with access to care, and the spectrum of HIV-related chronic kidney disease now reflects the growing burden of comorbid disease in the aging HIV population. Nonetheless, available data suggest that both HIV infection and cART nephrotoxicity continue to contribute to the increased risk of chronic kidney disease in HIV-infected individuals in the United States and Europe. Despite the genetic susceptibility to HIVAN in individuals of West African descent, limited data are available to define the prevalence and spectrum of HIV-related kidney disease in sub-Saharan Africa, which is home to two-thirds of the world's HIV population. In this mini-review, we characterize the changing epidemiology of HIV-related chronic kidney disease in Western nations and in sub-Saharan Africa.
Topics: AIDS-Associated Nephropathy; Africa South of the Sahara; Anti-HIV Agents; Coinfection; Diabetes Complications; Hepatitis C, Chronic; Humans; Hypertension; Renal Insufficiency, Chronic; United States
PubMed: 24573317
DOI: 10.1038/ki.2014.44 -
Journal of Investigative Medicine High... 2024BK virus (BKV) is a small DNA virus, a member of the polyomavirus family, that causes an opportunistic infection in immunocompromised patients, especially kidney... (Review)
Review
BK virus (BKV) is a small DNA virus, a member of the polyomavirus family, that causes an opportunistic infection in immunocompromised patients, especially kidney transplant patients. This virus establishes a lifelong infection in most of the population, and once it reactivates in an immunocompromised state, leads to BKV nephropathy. This review seeks to assess the correlation between severe immunosuppression, evident by low CD4 cell counts in HIV-positive patients, and the reactivation of BKV, causing nephropathy. A literature review was conducted, extracting, and analyzing case reports of HIV-positive patients showing correlations between their degree of immunosuppression, as evidenced by their CD4 counts, and the degree of BKV infectivity, confirmed by kidney biopsy. A total of 12 cases of BKV nephropathy in HIV-infected patients were reviewed. A common finding was the presence of profound immunosuppression, with most patients having CD4 counts ≤50 cells/ mm. A substantial number also had comorbid malignancies, with some undergoing chemotherapy, potentially increasing the risk of BKV reactivation. In addition to the HIV status and malignancies, other risk factors for BKV reactivation included older age, male gender, diabetes mellitus, Caucasian race, and ureteral stent placement. BKV nephropathy in HIV patients with native kidneys is closely correlated with severe immunosuppression. Although therapeutic strategies exist for post-transplant patients, aside from the treatment of HIV with highly active anti-retroviral therapy (HAART), which potentially helps with clearing BKV by increasing CD4 count, there is no definitive treatment for a native kidney BKV nephropathy in patients with AIDS. The complexity of the cases and severity of comorbidities indicate the need for further research to develop therapeutic strategies tailored to this population.
Topics: Humans; Male; BK Virus; HIV Infections; Acquired Immunodeficiency Syndrome; Kidney; Neoplasms; Polyomavirus Infections
PubMed: 38375628
DOI: 10.1177/23247096241232202 -
APOL1 Risk Variants Are Strongly Associated with HIV-Associated Nephropathy in Black South Africans.Journal of the American Society of... Nov 2015APOL1 variants are associated with HIV-associated nephropathy and FSGS in African Americans. The prevalence of these variants in African populations with CKD in HIV-1...
APOL1 variants are associated with HIV-associated nephropathy and FSGS in African Americans. The prevalence of these variants in African populations with CKD in HIV-1 infection has not been investigated. We determined the role of APOL1 variants in 120 patients with HIV-associated nephropathy and CKD and 108 controls from a South-African black population. Patients with CKD were selected on the basis of histology. Genotypes were successfully determined for APOL1 G1 and G2 variants and 42 single nucleotide polymorphisms, including 18 ancestry informative markers, for 116 patients with CKD (96.7%; 38 patients with HIV-associated nephropathy, 39 patients with HIV-positive CKD, and 39 patients with HIV-negative CKD), and 108 controls (100%). Overall, 79% of patients with HIV-associated nephropathy and 2% of population controls carried two risk alleles. In a recessive model, individuals carrying any combination of two APOL1 risk alleles had 89-fold higher odds (95% confidence interval, 18 to 912; P<0.001) of developing HIV-associated nephropathy compared with HIV-positive controls. Population allele frequencies were 7.3% for G1 and 11.1% for G2. APOL1 risk alleles were not significantly associated with other forms of CKD. These results indicate HIV-positive, antiretroviral therapy-naïve South-African blacks with two APOL1 risk alleles are at very high risk for developing HIV-associated nephropathy. Further studies are required to determine the effect of APOL1 risk variants on kidney diseases in other regions of sub-Saharan Africa.
Topics: AIDS-Associated Nephropathy; Adult; Alleles; Apolipoprotein L1; Apolipoproteins; Black People; Female; Gene Frequency; Genetic Predisposition to Disease; Genetic Variation; Genotype; Glomerular Filtration Rate; Haplotypes; Humans; Inflammation; Linkage Disequilibrium; Lipoproteins, HDL; Male; Odds Ratio; Phenotype; Polymorphism, Single Nucleotide; Prevalence; Risk Factors; South Africa
PubMed: 25788523
DOI: 10.1681/ASN.2014050469 -
Internal Medicine (Tokyo, Japan) May 2021Objective A kidney biopsy is generally performed in diabetic patients to discriminate between diabetic nephropathy (DN) and non-diabetic kidney disease (NDKD) and to...
Objective A kidney biopsy is generally performed in diabetic patients to discriminate between diabetic nephropathy (DN) and non-diabetic kidney disease (NDKD) and to provide more specific treatments. This study investigated the impact of anemia on the renal pathology and the clinical course in patients who underwent a kidney biopsy. Methods We reviewed 81 patients with type 2 diabetes who underwent a percutaneous kidney biopsy. Patients were classified into two groups: isolated DN (DN group, n=30) and NDKD alone or concurrent DN (NDKD group, n=51) groups. The laboratory and pathological findings and clinical courses were investigated. Results In the NDKD group, membranous nephropathy was the most common finding (23.5%), followed by IgA nephropathy (17.6%) and crescentic glomerulonephritis (13.7%). In the logistic regression analysis, the absence of severe hematuria and presence of anemia were significantly associated with a diagnosis of DN. Akaike's information criterion (AIC) and net reclassification improvement (NRI) analyses revealed improved predictive performance by adding anemia to the conventional factors (AIC 100.152 to 91.844; NRI 27.0%). The tissues of patients in the DN group demonstrated more severe interstitial fibrosis and tubular atrophy (IF/TA) than those in the NDKD group (p<0.05) regardless of the rate of global glomerulosclerosis, and IF/TA was related to the prevalence of anemia (odds ratio: 7.31, 95% confidence interval: 2.33-23.00, p<0.01) according to a multivariable regression analysis. Furthermore, the isolated DN group demonstrated a poorer prognosis than the NDKD group. Conclusion DN is associated with anemia because of severe IF/TA regardless of the renal function, and anemia helps clinician discriminate clinically between isolated DN and NDKD.
Topics: Anemia; Biopsy; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Glomerulonephritis, IGA; Humans; Kidney
PubMed: 33250462
DOI: 10.2169/internalmedicine.5455-20 -
PloS One 2022The spectrum of HIV-associated kidney disease has expanded significantly with the introduction of antiretroviral therapy (ART). In the pre-ART era there was prominence...
The spectrum of HIV-associated kidney disease has expanded significantly with the introduction of antiretroviral therapy (ART). In the pre-ART era there was prominence of HIV-associated nephropathy (HIVAN). More recently, the spectrum of disease additionally reflects comorbid illness in the ageing HIV population and ART-related nephrotoxicity. We performed a clinicopathological correlation of kidney disease in HIV-positive individuals who underwent kidney biopsy between 1989 and 2014, utilizing the 2018 Kidney Disease Improving Global Outcomes pathologic classification. ART rollout began in 2004 in South Africa. Patients biopsied pre-ART rollout were compared to those biopsied post-ART rollout with respect to demographics, clinical parameters and histology. We assessed kidney survival in a cohort of these patients following biopsy. Six hundred and ninety biopsies were included, 99 (14.3%) were undertaken pre- and 591 (85.7%) post-ART rollout. Most patients were of Black African descent (97.5%). The post-ART rollout patients were older (p = 0.007), had higher eGFR at presentation (p = 0.016) and fewer presented with eGFR of less than 15ml/min/1.73m2 (p = 0.0008). There was a decrease in the prevalence of classic HIVAN (p = 0.00001); and an increase in FSGS (NOS) in the setting of HIV (p = 0.0022) and tubulointerstitial diseases (p = 0.009) post-ART rollout. Kidney function survival over 5 years was poorest in patients with classic HIVAN (p = 0.00005) and best in minimal change nephropathy (p = 0.0013). Kidney biopsy is crucial for the correct diagnosis and management of HIV-related kidney disease. ART rollout has shifted the spectrum of kidney disease away from classic HIVAN but has not eliminated it. Histological diagnosis prognosticates kidney survival.
Topics: AIDS-Associated Nephropathy; Cohort Studies; HIV Infections; Humans; Kidney; Prevalence
PubMed: 35639767
DOI: 10.1371/journal.pone.0269260