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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 -
Viruses Apr 2022The achievement of an HIV cure is dependent on the eradication or permanent silencing of HIV-latent viral reservoirs, including the understudied central nervous system...
The achievement of an HIV cure is dependent on the eradication or permanent silencing of HIV-latent viral reservoirs, including the understudied central nervous system (CNS) reservoir. This requires a deep understanding of the molecular mechanisms of HIV's entry into the CNS, latency establishment, persistence, and reversal. Therefore, representative CNS culture models that reflect the intercellular dynamics and pathophysiology of the human brain are urgently needed in order to study the CNS viral reservoir and HIV-induced neuropathogenesis. In this study, we characterized a human cerebral organoid model in which microglia grow intrinsically as a CNS culture model to study HIV infection in the CNS. We demonstrated that both cerebral organoids and isolated organoid-derived microglia (oMG), infected with replication-competent HIVbal reporter viruses, support productive HIV infection via the CCR5 co-receptor. Productive HIV infection was only observed in microglial cells. Fluorescence analysis revealed microglia as the only HIV target cell. Susceptibility to HIV infection was dependent on the co-expression of microglia-specific markers and the CD4 and CCR5 HIV receptors. Altogether, this model will be a valuable tool within the HIV research community to study HIV-CNS interactions, the underlying mechanisms of HIV-associated neurological disorders (HAND), and the efficacy of new therapeutic and curative strategies on the CNS viral reservoir.
Topics: AIDS-Associated Nephropathy; HIV Infections; HIV-1; Humans; Microglia; Organoids; Receptors, HIV
PubMed: 35458559
DOI: 10.3390/v14040829 -
Journal of the International... 2022Kidney disease is the fourth most common cause of non-AIDS-related mortality in people living with HIV. Combination antiretroviral therapy (cART) remains the cornerstone...
Kidney disease is the fourth most common cause of non-AIDS-related mortality in people living with HIV. Combination antiretroviral therapy (cART) remains the cornerstone of treatment. However, little is known about the impact of cART on disease outcomes in patients with HIV-associated nephropathy (HIVAN) and HIV-immune complex kidney disease (HIVICK). This systematic review evaluates the impact of cART on progression to end-stage kidney disease (ESKD) and other outcomes in HIV-infected individuals. We conducted a literature search utilizing PubMed, and Cochrane database and 11 articles met inclusion criteria for analysis of which nine HIVAN studies showed decreased progression to ESKD or death for subjects when treated with cART versus those untreated. However, two studies showed no survival advantage with cART. Three HIVICK studies showed improvement in delaying ESKD in subjects on cART compared to untreated subjects. cART appeared to reduce the risk to ESKD or death in patients with both HIVAN and HIVICK.
Topics: AIDS-Associated Nephropathy; HIV Infections; Humans
PubMed: 35369795
DOI: 10.1177/23259582221089194 -
HIV Medicine Mar 2022HIV-associated kidney disease is common but data on the pathology spectrum of kidney biopsy in China is lacking. This study aimed to illustrate the clinical...
OBJECTIVES
HIV-associated kidney disease is common but data on the pathology spectrum of kidney biopsy in China is lacking. This study aimed to illustrate the clinical presentation, laboratory findings and pathological spectrum of different subtypes of HIV-associated kidney disease in China.
METHODS
Eighteen HIV patients with renal biopsy indications at the Peking Union Medical College Hospital from January 2002 to October 2021 were retrospectively enrolled. All had CD4 counts and HIV viral load measurements. Renal biopsies were examined with light microscopy, immunofluorescence, and electron microscopy. Shapiro-Wilk test was used to test whether the data was normally distributed. The data is presented as medians (interquartile range), number (%), or means (±SD) according to their distribution.
RESULTS
Seventeen patients had glomerular disease, and one patient had interstitial nephritis. Membranous nephropathy was present in eight patients (47.1%), and IgA nephropathy in four patients (23.5%). The difference in urine protein and serum albumin before and after treatment was statistically significant and no deaths or dialysis were observed to the end of follow-up.
CONCLUSION
This study found that classic HIV-associated nephropathy (HIVAN) was uncommon in Chinese HIV patients. HIV immune complex kidney (HIVICK) disease, such as membranous or IgA nephropathy, was more common, and associated with better prognosis. Antiretroviral therapy, ACE inhibitors, and angiotensin II receptor blockers were effective in decreasing proteinuria and preserving renal function. The use of corticosteroids and immunosuppressive agents seems safe. However, the nephrotoxic effect of antiretroviral agents and other medications should be carefully monitored.
Topics: AIDS-Associated Nephropathy; Biopsy; Female; Glomerulonephritis, IGA; HIV Infections; Humans; Kidney; Male; Retrospective Studies
PubMed: 35293105
DOI: 10.1111/hiv.13246 -
Journal of the American Society of... Jan 2022To gain insight into the pathogenesis of collapsing glomerulopathy, a rare form of FSGS that often arises in the setting of viral infections, we performed a genome-wide...
BACKGROUND
To gain insight into the pathogenesis of collapsing glomerulopathy, a rare form of FSGS that often arises in the setting of viral infections, we performed a genome-wide association study (GWAS) among inbred mouse strains using a murine model of HIV-1 associated nephropathy (HIVAN).
METHODS
We first generated F1 hybrids between HIV-1 transgenic mice on the FVB/NJ background and 20 inbred laboratory strains. Analysis of histology, BUN, and urinary NGAL demonstrated marked phenotypic variation among the transgenic F1 hybrids, providing strong evidence for host genetic factors in the predisposition to nephropathy. A GWAS in 365 transgenic F1 hybrids generated from these 20 inbred strains was performed.
RESULTS
We identified a genome-wide significant locus on chromosome 13-C3 and multiple additional suggestive loci. Crossannotation of the Chr. 13 locus, including single-cell transcriptomic analysis of wildtype and HIV-1 transgenic mouse kidneys, nominated as the most likely candidate gene. is highly expressed in podocytes, encodes a transcriptional cofactor that interacts with LDB1 and LMX1B, which are both previously implicated in FSGS. Consistent with these data, older null mice spontaneously develop glomerulosclerosis, tubular casts, interstitial fibrosis, and inflammation, similar to the HIVAN mouse model.
CONCLUSIONS
These findings demonstrate the utility of GWAS in mice to uncover host genetic factors for rare kidney traits and suggest as susceptibility gene for HIVAN, potentially acting the LDB1-LMX1B transcriptional network.
Topics: AIDS-Associated Nephropathy; Animals; DNA-Binding Proteins; Disease Models, Animal; Female; Genetic Loci; Genetic Predisposition to Disease; Genome-Wide Association Study; Glomerulosclerosis, Focal Segmental; Male; Mice; Mice, Transgenic
PubMed: 34893534
DOI: 10.1681/ASN.2021040543 -
Journal of Clinical Virology : the... Jan 2022There are limited data about the use and clinical value of JC polyomavirus (JCPyV) DNA detection in various clinical indications.
BACKGROUND
There are limited data about the use and clinical value of JC polyomavirus (JCPyV) DNA detection in various clinical indications.
METHODS
We reviewed the clinical records of 410 patients from whom cerebrospinal fluid (CSF), plasma, urine, or tissue samples had been collected for JCPyV DNA polymerase chain reaction (PCR) between 2012 and 2018.
RESULTS
JCPyV DNA was analyzed in 224 plasma, 190 CSF-, 32 urine and 10 tissue samples. 240 patients had a history of hematopoietic stem cell or solid organ transplantation, 159 had nephrological disease, 90 had hematologic malignancies, 58 had neurological disease, 37 had infectious disease and 23 had AIDS/HIV as underlying disease. Six patients had no underlying disease. The main reasons to take CSF or plasma samples were neurological symptoms of unknown etiology. Most urine samples were taken to monitor kidney transplantation patients. JCPyV DNA PCR contributed to the diagnosis of progressive multifocal leukoencephalopathy in eight patients (2.0%), of which seven had hematologic malignancy as an underlying disease.
CONCLUSIONS
JCPyV PCR is most informative among immunosuppressed patients with neurologic symptoms. CSF and brain biopsy are useful when there is clinical suspicion of PML, whereas plasma samples are not useful. The value of plasma samples is a matter of dispute in the screening of JCPyV-associated nephropathy, as BK polyomavirus is the causative agent in most polyomavirus-associated nephropathy cases. JCPyV detection is valuable in case the patient has past, current or planned treatment with immunosuppressive drugs.
Topics: BK Virus; DNA, Viral; Humans; JC Virus; Leukoencephalopathy, Progressive Multifocal; Polyomavirus; Polyomavirus Infections
PubMed: 34883406
DOI: 10.1016/j.jcv.2021.105051 -
Cureus Oct 2021In the wake of highly active antiretroviral therapy (HAART), kidney transplantation has become common practice in HIV-positive recipients. However, management is more...
In the wake of highly active antiretroviral therapy (HAART), kidney transplantation has become common practice in HIV-positive recipients. However, management is more complex than that of a seronegative recipient in the pre-operative, peri-operative, and post-operative periods. Although the standard HAART regimen is often modified to improve outcomes and reduce interactions with the post-transplant immunosuppressive regimen, kidney transplantation in HIV-positive individuals is feasible, with high graft survival rates comparable to those in their seronegative counterparts. There is also increasing interest in the possibility of HIV-positive kidney donation, which could increase the donor pool in seropositive patients with end-stage renal disease. This report highlights considerations in the management of a seropositive kidney recipient, reviewing the evidence that underpins current treatment guidelines and highlighting the role of HAART in the dramatic change in attitude towards transplantation in this population. It also addresses studies from multiple countries which have shown favourable outcomes in transplants from HIV-positive donors. This warrants further investigation into seropositive-to-seropositive transplantation as a potential therapeutic option.
PubMed: 34659933
DOI: 10.7759/cureus.18744 -
Frontiers in Endocrinology 2021Globally, nearly 40 percent of all diabetic patients develop serious diabetic kidney disease (DKD). The identification of the potential early-stage biomarkers and...
Globally, nearly 40 percent of all diabetic patients develop serious diabetic kidney disease (DKD). The identification of the potential early-stage biomarkers and elucidation of their underlying molecular mechanisms in DKD are required. In this study, we performed integrated bioinformatics analysis on the expression profiles GSE111154, GSE30528 and GSE30529 associated with early diabetic nephropathy (EDN), glomerular DKD (GDKD) and tubular DKD (TDKD), respectively. A total of 1,241, 318 and 280 differentially expressed genes (DEGs) were identified for GSE30258, GSE30529, and GSE111154 respectively. Subsequently, 280 upregulated and 27 downregulated DEGs shared between the three GSE datasets were identified. Further analysis of the gene expression levels conducted on the hub genes revealed SPARC (Secreted Protein Acidic And Cysteine Rich), POSTN (periostin), LUM (Lumican), KNG1 (Kininogen 1), FN1 (Fibronectin 1), VCAN (Versican) and PTPRO (Protein Tyrosine Phosphatase Receptor Type O) having potential roles in DKD progression. FN1, LUM and VCAN were identified as upregulated genes for GDKD whereas the downregulation of PTPRO was associated with all three diseases. Both POSTN and SPARC were identified as the overexpressed putative biomarkers whereas KNG1 was found as downregulated in TDKD. Additionally, we also identified two drugs, namely pidorubicine, a topoisomerase inhibitor (LINCS ID- BRD-K04548931) and Polo-like kinase inhibitor (LINCS ID- BRD-K41652870) having the validated role in reversing the differential gene expression patterns observed in the three GSE datasets used. Collectively, this study aids in the understanding of the molecular drivers, critical genes and pathways that underlie DKD initiation and progression.
Topics: Computational Biology; Datasets as Topic; Diabetic Nephropathies; Drug Evaluation, Preclinical; Gene Expression Profiling; Gene Ontology; Gene Regulatory Networks; Genetic Association Studies; High-Throughput Screening Assays; Humans; Protein Interaction Maps; Systems Integration; Transcriptome
PubMed: 34557161
DOI: 10.3389/fendo.2021.721202 -
BMC Nephrology Sep 2021HIV subjects have several kidney pathologies, like HIV-associated nephropathy or antiretroviral therapy injury, among others. The global prevalence of Chronic Kidney...
BACKGROUND
HIV subjects have several kidney pathologies, like HIV-associated nephropathy or antiretroviral therapy injury, among others. The global prevalence of Chronic Kidney Disease (CKD) is 8-16%; however, in HIV subjects, the prevalence varies between geographic regions (2-38%). The aim was to determine the prevalence of CKD and identify the associated risk factors.
METHODS
A longitudinal descriptive study was carried out at the 'Hospital Civil de Guadalajara' Feb'18 - Jan'19. Basal clinical, demographic, opportunistic infections (OI), and laboratory data were obtained at months 0 and 3; inclusion criteria were ≥ 18 years old, naïve HIV + , urine albumin/creatinine ratio, serum creatinine & urine test, and signed informed consent. Descriptive and multiple logistic regression statistical analyses were made.
RESULTS
One hundred twenty subjects were included; 92.5% were male, 33 ± 9.5 years, 60% consumed tobacco, 73% alcohol, and 59% some type of drug. The CKD prevalence was 15.8%. CKD patients had a higher risk of hepatitis C virus coinfection, Relative Risk (RR):5.9; HCV infection, RR:4.3; ≥ 30 years old, RR:3.9; C clinical-stage, RR:3.5; CD4 T cells count < 200 cells/μL, RR: 2.4; and HIV-1 viral load ≥ 100,000 cop/mL, RR: 2.7.
CONCLUSIONS
Our study showed a higher CKD prevalence in patients with HIV; higher CKD development with coinfections as Hepatitis C Virus and Mycobacterium tuberculosis. The identification and prompt management of CKD and coinfections should be considered to avoid the progression and to delay renal replacement therapy as long as possible.
Topics: AIDS-Associated Nephropathy; Adult; CD4 Lymphocyte Count; CD4-CD8 Ratio; Coinfection; Female; HIV Seropositivity; HIV-1; Humans; Male; Mexico; Prevalence; Renal Insufficiency, Chronic; Risk Factors; Viral Load
PubMed: 34556049
DOI: 10.1186/s12882-021-02526-4 -
Frontiers in Medicine 2021Variants in the () gene (G1-rs60910145, rs73885319, G2-rs71785313) are common in Africans and in individuals of recent African ancestry and are associated with an...
Variants in the () gene (G1-rs60910145, rs73885319, G2-rs71785313) are common in Africans and in individuals of recent African ancestry and are associated with an increased risk of non-diabetic chronic kidney disease (CKD) and in particular of HIV associated nephropathy (HIVAN). In light of the significantly increased risk of HIVAN in carriers of two risk alleles, a role in HIV infectivity has been postulated in the mechanism of associated kidney disease. Herein, we aim to explore the association between HIV viremia and genotype. In addition, we investigated interaction between BK and JC viruria, CKD and HIV viremia. A total of 199 persons living with HIV/AIDS (comprising 82 CKD cases and 117 controls) from among the participants in the ongoing Human Heredity and Health in Africa (H3Africa) Kidney Disease Research Network case control study have been recruited. The two renal risk alleles (RRA) genotypes were associated with a higher risk of CKD (OR 12.6, 95% CI 3.89-40.8, < 0.0001). Even a single APOL1 RRA was associated with CKD risk (OR 4.42, 95% CI 1.49-13.15, = 0.007). The 2 APOL1 RRA genotypes were associated with an increased probability of having HIV viremia (OR 2.37 95% CI 1.0-5.63, = 0.05). HIV viremia was associated with increased CKD risk (OR 7.45, 95% CI 1.66-33.35, = 0.009) and with a significant reduction of JC virus urine shedding (OR 0.35, 95% CI 0.12-0.98, = 0.046). In contrast to prior studies, JC viruria was not associated with CKD but was restricted in patients with HIV viremia, regardless of CKD status. These findings suggest a role of variants in HIV infectivity and emphasize that JC viruria can serve as biomarker for innate immune system activation.
PubMed: 34513880
DOI: 10.3389/fmed.2021.718300