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Wiadomosci Lekarskie (Warsaw, Poland :... 2021The aim is to verify and describe the morphological substrate of renal impairment in HIV/HCV co-infection among patients receiving ART to assess and predict the...
OBJECTIVE
The aim is to verify and describe the morphological substrate of renal impairment in HIV/HCV co-infection among patients receiving ART to assess and predict the morphogenesis of immunocomplex lesions.
PATIENTS AND METHODS
Materials and methods: To assess and predict the morphogenesis of immunocomplex renal disease, we examined retrospectively the kidney tissue samples of 15 patients, who died with HIV/HCV co-infection and received ART. Histological, histochemical and immunohistochemical research methods were used.
RESULTS
Results: Segmental and diffuse mesangial proliferation with extracellular matrix expansion with glomerular damage ≥50% in 9 (60%) cases, and involving <50% of glomeruli in 5 (33%), with CD68 expression as single cells were detected. In 12 (80%) cases, there was uneven swelling and focal proliferation of endothelial cells with the involvement of 20-50% of the glomeruli, as well as the presence of cellular infiltrates in the lumen of capillary loops in 3 (20%) cases with monomorphic intensity in "+". Sclerotic changes were present in various degrees of severity - from cases of complete glomerulosclerosis with obliteration of the Bowman's lumen to focal and microfocal depressions 8 (55%), sclerosis 10 (66%), hyalinosis 1 (6%), uneven thickening, focal cleft 8 (55%) and perihilar focal sclerosis. These areas were positive for IgG and C1q complement fractions within the "+", "++" intensity. Among the study group, no case of HIV-associated nephropathy was found that coincided with the predicted spectrum of kidney damage for patients in this sample. The described morphological changes were mainly verified as immuno-mediated by HCV.
CONCLUSION
Conclusions: A comprehensive morphological study revealed the morphological substrate of kidney damage and its morphogenesis in patients with HIV/HCV co-infection, receiving ART.
Topics: AIDS-Associated Nephropathy; Endothelial Cells; Glomerulosclerosis, Focal Segmental; HIV Infections; Hepacivirus; Hepatitis C; Humans; Retrospective Studies
PubMed: 34459751
DOI: No ID Found -
Arteriosclerosis, Thrombosis, and... Jan 2021To determine the effects of HIV serostatus and disease severity on endothelial function in a large pooled cohort study of people living with HIV infection and HIV-...
OBJECTIVE
To determine the effects of HIV serostatus and disease severity on endothelial function in a large pooled cohort study of people living with HIV infection and HIV- controls. Approach and Results: We used participant-level data from 9 studies: 7 included people living with HIV (2 treatment-naïve) and 4 had HIV- controls. Brachial artery flow-mediated dilation (FMD) was measured using a standardized ultrasound imaging protocol with central reading. After data harmonization, multiple linear regression was used to examine the effects of HIV- serostatus, HIV disease severity measures, and cardiovascular disease risk factors on FMD. Of 2533 participants, 986 were people living with HIV (mean 44.4 [SD 11.8] years old) and 1547 were HIV- controls (42.9 [12.2] years old). The strongest and most consistent associates of FMD were brachial artery diameter, age, sex, and body mass index. The effect of HIV+ serostatus on FMD was strongly influenced by kidney function. In the highest tertile of creatinine (1.0 mg/dL), the effect of HIV+ serostatus was strong (β=-1.59% [95% CI, -2.58% to -0.60%], =0.002), even after covariate adjustment (β=-1.36% [95% CI, -2.46% to -0.47%], =0.003). In the lowest tertile (0.8 mg/dL), the effect of HIV+ serostatus was strong (β=-1.90% [95% CI, -2.58% to -1.21%], <0.001), but disappeared after covariate adjustment. HIV RNA viremia, CD4+ T-cell count, and use of antiretroviral therapy were not meaningfully associated with FMD.
CONCLUSIONS
The significant effect of HIV+ serostatus on FMD suggests that people living with HIV are at increased cardiovascular disease risk, especially if they have kidney disease.
Topics: AIDS Serodiagnosis; AIDS-Associated Nephropathy; Adolescent; Adult; Aged; Brachial Artery; Cardiovascular Diseases; Case-Control Studies; Endothelium, Vascular; Female; HIV Infections; HIV Seronegativity; HIV Seropositivity; Heart Disease Risk Factors; Humans; Male; Middle Aged; Predictive Value of Tests; Risk Assessment; Severity of Illness Index; Vasodilation; Young Adult
PubMed: 33327750
DOI: 10.1161/ATVBAHA.120.315435 -
Systematic Reviews May 2024IgA nephropathy (IgAN) is a common cause of chronic kidney disease (CKD) and end-stage renal disease (ESRD). Outcomes are highly variable and predicting risk of disease...
BACKGROUND
IgA nephropathy (IgAN) is a common cause of chronic kidney disease (CKD) and end-stage renal disease (ESRD). Outcomes are highly variable and predicting risk of disease progression at an individual level is challenging. Accurate risk stratification is important to identify individuals most likely to benefit from treatment. The Kidney Failure Risk Equation (KFRE) has been extensively validated in CKD populations and predicts the risk of ESRD at 2 and 5 years using non-invasive tests; however, its predictive performance in IgAN is unknown. The Oxford classification (OC) describes pathological features demonstrated on renal biopsy that are associated with adverse clinical outcomes that may also inform prognosis. The objective of this systematic review is to compare the KFRE with the OC in determining prognosis in IgAN.
METHODS
A systematic review will be conducted and reported in line with PRISMA guidelines (PRISMA-P checklist attached as Additional file 1). Inclusion criteria will be cohort studies that apply the KFRE or OC to determine the risk of CKD progression or ESRD in individuals with IgAN. Multiple databases will be searched in duplicate to identify relevant studies, which will be screened first by title, then by abstract and then by full-text analysis. Results will be collated for comparison. Risk of bias and confidence assessments will be conducted independently by two reviewers, with a third reviewer available if required.
DISCUSSION
Identifying individuals at the highest risk of progression to ESRD is challenging in IgAN, due to the heterogeneity of clinical outcomes. Risk prediction tools have been developed to guide clinicians; however, it is imperative that these aids are accurate and reproducible. The OC is based on observations made by specialist renal pathologists and may be open to observer bias, therefore the utility of prediction models incorporating this classification may be diminished, particularly as in the future novel biomarkers may be incorporated into clinical practice.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO CRD42022364569.
Topics: Humans; Glomerulonephritis, IGA; Prognosis; Systematic Reviews as Topic; Disease Progression; Kidney Failure, Chronic; Risk Assessment; Renal Insufficiency, Chronic; Biopsy
PubMed: 38704598
DOI: 10.1186/s13643-024-02543-y -
AIDS (London, England) Aug 2019Many of those aging with HIV suffer from distal neuropathic pain (DNP) due to HIV-associated sensory neuropathy (HIV-SN). Prior studies have linked chronic pain... (Observational Study)
Observational Study
BACKGROUND
Many of those aging with HIV suffer from distal neuropathic pain (DNP) due to HIV-associated sensory neuropathy (HIV-SN). Prior studies have linked chronic pain conditions to a variant of the catechol-O-methyltransferase (COMT), ValMet. This variant confers reduced enzymatic activity and results in higher synaptic dopamine levels. Here we examined the role of ValMet as a predictor of DNP in HIV-SN.
METHODS
In 1044 HIV-infected individuals enrolled in CNS HIV Antiretroviral Therapy Effects Research, an observational study across six US institutions, we characterized the relationship between ValMet and DNP in HIV-SN. Participants underwent neurologic examination and genotyping. Stratification into genetic ancestry groups was employed to eliminate bias due to genetic background.
FINDINGS
Of 590 participants with HIV-SN, 38% endorsed DNP, 24% reported nonpainful symptoms of neuropathy (paresthesia and numbness), and 38% were asymptomatic. Compared with asymptomatic HIV-SN, ValMet was associated with 2.3 higher odds of DNP. There were no increased odds of nonpainful symptoms. The association remained significant after controlling for other risk factors for DNP: lifetime diagnosis of depression, older age, ancestry, cumulative exposure to dideoxynucleoside antiretrovirals, diabetes, and nadir CD4. Stratified by genetic ancestry, the association between ValMet and DNP was significant in European and African genetic ancestry.
INTERPRETATION
ValMet may be a genetic marker for susceptibility to DNP in HIV-SN. Our findings support the notion that differences in pain processing mediated by COMT-related dopamine signaling play a role in susceptibility to DNP in HIV-SN. Because prior studies suggest that the COMT allele may influence dose-response relationships with opioid treatment, knowing COMT genotype could influence management.
Topics: AIDS-Associated Nephropathy; Adult; Amino Acid Substitution; Catechol O-Methyltransferase; Female; Genetic Predisposition to Disease; Genotype; Genotyping Techniques; HIV Infections; Humans; Male; Methionine; Middle Aged; Neuralgia; Polymorphism, Single Nucleotide; Prospective Studies; United States; Valine
PubMed: 31021849
DOI: 10.1097/QAD.0000000000002240 -
Cureus Aug 2019Human immunodeficiency virus (HIV) infection presents with a variety of conditions. We describe the case of a 33-year-old Hispanic male with IgA nephropathy and...
Human immunodeficiency virus (HIV) infection presents with a variety of conditions. We describe the case of a 33-year-old Hispanic male with IgA nephropathy and Henoch-Schonlein Purpura in the setting of HIV. The incidence of vasculitis associated with HIV infection is less than 1%. There are few cases reported of IgA nephropathy in the context of HIV. Henoch-Schonlein Purpura usually presents in children. We encountered a patient with rare illnesses while in the setting of immunodeficiency.
PubMed: 31612096
DOI: 10.7759/cureus.5368 -
Medical Ultrasonography Nov 2020A 62-year-old woman who underwent kidney transplantation in 2014 was diagnosed with HIV infection in 2018. Grey scale and Doppler ultrasound evaluation revealed a normal...
A 62-year-old woman who underwent kidney transplantation in 2014 was diagnosed with HIV infection in 2018. Grey scale and Doppler ultrasound evaluation revealed a normal aspect of the allograft. Contrast-enhanced ultrasound detected a quick cortical contrast uptake followed by a rapid cortical wash-out. This behavior was interpreted as a sign of inflammation. Ten months after ultrasound evaluation the graft presented severe disfunction and the patient was reintroduced into the hemodialysis program.
Topics: AIDS-Associated Nephropathy; Contrast Media; Female; HIV Infections; Humans; Kidney; Kidney Transplantation; Middle Aged
PubMed: 32190861
DOI: 10.11152/mu-2314 -
The Journal of Pain 2020Numerous studies have demonstrated a physiological interaction between the mu opioid receptor (MOR) and delta opioid receptor (DOR) systems. A few studies have shown...
Numerous studies have demonstrated a physiological interaction between the mu opioid receptor (MOR) and delta opioid receptor (DOR) systems. A few studies have shown that dual MOR-DOR agonists could be beneficial, with reduced tolerance and addiction liability, but are nearly untested in chronic pain models, particularly neuropathic pain. In this study, we tested the MOR-DOR agonist SRI-22141 in mice in the clinically relevant models of HIV Neuropathy and Chemotherapy-Induced Peripheral Neuropathy (CIPN). SRI-22141 was more potent than morphine in the tail flick pain test and had equal or enhanced efficacy versus morphine in both neuropathic pain models, with significantly reduced tolerance. SRI-22141 also produced no jumping behavior during naloxone-precipitated withdrawal in CIPN or naïve mice, suggesting that SRI-22141 produces little to no dependence. SRI-22141 also reduced tumor necrosis factor-α and cyclooxygenase-2 in CIPN in the spinal cord, suggesting an anti-inflammatory mechanism of action. The DOR-selective antagonist naltrindole strongly reduced CIPN efficacy and anti-inflammatory activity in the spinal cord, without affecting tail flick antinociception, suggesting the importance of DOR activity in these models. Overall, these results provide compelling evidence that MOR-DOR agonists could have strong efficacy with reduced side effects and an anti-inflammatory mechanism in the treatment of neuropathic pain. PERSPECTIVE: This study demonstrates that a MOR-DOR dual agonist given chronically in chronic neuropathic pain models has enhanced efficacy with strongly reduced tolerance and dependence, with a further anti-inflammatory effect in the spinal cord. This suggests that MOR-DOR dual agonists could be effective treatments for neuropathic pain with reduced side effects.
Topics: AIDS-Associated Nephropathy; Analgesics, Opioid; Animals; Anti-Inflammatory Agents; Behavior, Animal; Cell Line; Cricetulus; Disease Models, Animal; Female; Male; Mice; Mice, Inbred ICR; Neuralgia; Neurotoxicity Syndromes; Ovary; Receptors, Opioid, delta; Receptors, Opioid, mu
PubMed: 31201990
DOI: 10.1016/j.jpain.2019.05.017 -
Journal of Medical Case Reports Apr 2024Immunoglobulin G4-related disease is an inflammatory disease affecting multiple organs including the kidney. Immunoglobulin G4-related kidney disease most commonly...
BACKGROUND
Immunoglobulin G4-related disease is an inflammatory disease affecting multiple organs including the kidney. Immunoglobulin G4-related kidney disease most commonly manifests as a tubulointerstitial nephritis and is associated with glomerular disease in a proportion of cases. Membranous nephropathy is the most frequent glomerular lesion. Herein, we report the first documented case of immunoglobulin G4-related disease presenting with nephrotic syndrome owing to minimal change disease.
CASE PRESENTATION
A 67-year-old South Asian male presented to our service with systemic upset and leg swelling. He had heavy proteinuria (urine protein:creatinine ratio 1042 mg/mmol) and was hypoalbuminemic (17 g/L) and hypercholersterolemic (9.3 mmol/L), consistent with the nephrotic syndrome. His serum creatinine was 140 μmol/L, and he was hypocomplementemic (C3 0.59 g/L, C4 < 0.02 g/L) with raised immunoglobulin G4 subclass levels (5.29 g/L). Kidney biopsy demonstrated minimal change disease alongside a plasma-cell-rich tubulointerstitial nephritis with strong positive staining for immunoglobulin G4. A diagnosis of minimal change disease in the setting of immunoglobulin G4-related disease was made. He was commenced on oral prednisolone at 60 mg daily but suffered infectious complications, including necrotizing fasciitis within 3 weeks of starting treatment, ultimately resulting in his death 52 days after initial presentation.
CONCLUSION
This case highlights the potential for immunoglobulin G4-related disease to be associated with a spectrum of glomerular pathologies including minimal change disease. It adds to the differential diagnosis of secondary causes of minimal change disease, and moreover, aids as an important reminder of the potential complications of high-dose steroids used in its treatment.
Topics: Humans; Male; Aged; Immunoglobulin G4-Related Disease; Nephrotic Syndrome; Nephrosis, Lipoid; Nephritis, Interstitial; Immunoglobulin G
PubMed: 38641649
DOI: 10.1186/s13256-024-04494-3 -
HIV Medicine Oct 2019The use of combination antiretroviral therapy (cART) increases clinical uncertainty about changes in renal function. Specifically, little is known regarding the...
Effects of aging, baseline renal function and stage of HIV infection on post-treatment changes in renal function among HIV-infected patients: a retrospective cohort study.
OBJECTIVES
The use of combination antiretroviral therapy (cART) increases clinical uncertainty about changes in renal function. Specifically, little is known regarding the interaction of the effects of aging, baseline renal impairment, and stages of HIV infection on post-treatment changes in renal function.
METHODS
This analysis included 5533 HIV-infected patients on cART in 2004-2016. Progression to chronic kidney disease (CKD) was defined as either two consecutive estimated glomerular filtration rate (eGFR) measurements < 60 mL/min/1.73 m for baseline eGFR ≥ 60 mL/min/1.73 m (mild renal impairment or normal renal function) or a 25% decline for baseline eGFR < 60 mL/min/1.73 m (moderate renal impairment).
RESULTS
During follow-up (median 4.8 years), 130 (2.3%) of the patients progressed to CKD. A total of 20.1% of patients with baseline normal renal function progressed to mild renal impairment, while 74.0% of patients with baseline mild or moderate renal impairment improved to normal renal function. In multivariable analysis, a significant positive baseline-eGFR-by-World Health Organization (WHO)-stage interaction effect on progression to CKD in all patients was identified, indicating a cross-over effect from a reduced risk to an increased risk. A significant negative baseline-age-by-WHO-stage interaction effect on progression to mild renal impairment in patients with baseline normal renal function was identified, with adjusted hazard ratios progressively lower at older ages. In addition, there were significant associations with older age, lower baseline eGFR, Dai ethnic minority, and anaemia for both outcomes, hyperglycaemia for CKD only, and higher CD4 count, tenofovir and ritonavir-boosted lopinavir use for mild renal impairment only.
CONCLUSIONS
Our data suggest a complex pattern of renal function dynamics in patients on cART, which requires precise management with systematic monitoring of the interaction of the effects of sociodemographic, nephrological and HIV-specific clinical characteristics.
Topics: AIDS-Associated Nephropathy; Adult; Aging; Anti-HIV Agents; CD4 Lymphocyte Count; China; Disease Progression; Female; Glomerular Filtration Rate; Humans; Male; Middle Aged; Renal Insufficiency, Chronic; Retrospective Studies; Treatment Outcome
PubMed: 31274235
DOI: 10.1111/hiv.12763 -
International Journal of Molecular... Mar 2024Genetic variants in the protein-coding regions of APOL1 are associated with an increased risk and progression of chronic kidney disease (CKD) in African Americans....
Genetic variants in the protein-coding regions of APOL1 are associated with an increased risk and progression of chronic kidney disease (CKD) in African Americans. Hypoxia exacerbates CKD progression by stabilizing HIF-1α, which induces APOL1 transcription in kidney podocytes. However, the contribution of additional mediators to regulating APOL1 expression under hypoxia in podocytes is unknown. Here, we report that a transient accumulation of HIF-1α in hypoxia is sufficient to upregulate APOL1 expression in podocytes through a cGAS/STING/IRF3-independent pathway. Notably, IFI16 ablation impedes hypoxia-driven APOL1 expression despite the nuclear accumulation of HIF-1α. Co-immunoprecipitation assays indicate no direct interaction between IFI16 and HIF-1α. Our studies identify hypoxia response elements (HREs) in the APOL1 gene enhancer/promoter region, showing increased HIF-1α binding to HREs located in the APOL1 gene enhancer. Luciferase reporter assays confirm the role of these HREs in transcriptional activation. Chromatin immunoprecipitation (ChIP)-qPCR assays demonstrate that IFI16 is not recruited to HREs, and IFI16 deletion reduces HIF-1α binding to APOL1 HREs. RT-qPCR analysis indicates that IFI16 selectively affects APOL1 expression, with a negligible impact on other hypoxia-responsive genes in podocytes. These findings highlight the unique contribution of IFI16 to hypoxia-driven APOL1 gene expression and suggest alternative IFI16-dependent mechanisms regulating APOL1 gene expression under hypoxic conditions.
Topics: Humans; Apolipoprotein L1; Cell Hypoxia; Chromatin Immunoprecipitation; Hypoxia; Hypoxia-Inducible Factor 1, alpha Subunit; Nuclear Proteins; Phosphoproteins; Podocytes; Renal Insufficiency, Chronic
PubMed: 38542298
DOI: 10.3390/ijms25063324