scholarly journals Inhibition of apoptosis signal-regulating kinase 1 mitigates the pathogenesis of human immunodeficiency virus–associated nephropathy

2020 ◽  
Author(s):  
Anqun Chen ◽  
Jin Xu ◽  
Han Lai ◽  
Vivette D D’Agati ◽  
Tian-Jun Guan ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Kidney Disease ◽  
Renal Disease ◽  
Disease Progression ◽  
Kidney Diseases ◽  
Mitogen Activated Protein Kinase ◽  
Hiv Positive ◽  
Full Spectrum ◽  
Interstitial Inflammation ◽  
Immunodeficiency Virus

Abstract Background Chronic kidney disease (CKD) is a common cause of morbidity and mortality in human immunodeficiency virus (HIV)-positive individuals. Among the HIV-related kidney diseases, HIV-associated nephropathy (HIVAN) is a rapidly progressive renal disease characterized by collapsing focal glomerulosclerosis (GS), microcystic tubular dilation, interstitial inflammation and fibrosis. Although the incidence of end-stage renal disease due to HIVAN has dramatically decreased with the widespread use of antiretroviral therapy, the prevalence of CKD continues to increase in HIV-positive individuals. Recent studies have highlighted the role of apoptosis signal-regulating kinase 1 (ASK1) in driving kidney disease progression through the activation of p38 mitogen-activated protein kinase and c-Jun N-terminal kinase and selective ASK-1 inhibitor GS-444217 was recently shown to reduce kidney injury and disease progression in various experimental models. Therefore we examined the efficacy of ASK1 antagonism by GS-444217 in the attenuation of HIVAN in Tg26 mice. Methods GS-444217-supplemented rodent chow was administered in Tg26 mice at 4 weeks of age when mild GS and proteinuria were already established. After 6 weeks of treatment, the kidney function assessment and histological analyses were performed and compared between age- and gender-matched control Tg26 and GS-444217-treated Tg26 mice. Results GS-444217 attenuated the development of GS, podocyte loss, tubular injury, interstitial inflammation and renal fibrosis in Tg26 mice. These improvements were accompanied by a marked reduction in albuminuria and improved renal function. Taken together, GS-4442217 attenuated the full spectrum of HIVAN pathology in Tg26 mice. Conclusions ASK1 signaling cascade is central to the development of HIVAN in Tg26 mice. Our results suggest that the select inhibition of ASK1 could be a potential adjunctive therapy for the treatment of HIVAN.

scholarly journals An Evaluation of Baseline Kidney Function in the REPRIEVE Trial of Pitavastatin in Human Immunodeficiency Virus

2020 ◽  
Vol 222 (Supplement_1) ◽  
pp. S41-S51
Author(s):  
Edgar T Overton ◽  
Amy Kantor ◽  
Kathleen V Fitch ◽  
Paul Muntner ◽  
Khuanchai Supparatpinyo ◽  
...  
Keyword(s):  
Risk Factors ◽  
Body Mass Index ◽  
Chronic Kidney Disease ◽  
Human Immunodeficiency Virus ◽  
Kidney Disease ◽  
Renal Disease ◽  
Kidney Function ◽  
Factors Associated ◽  
Immunodeficiency Virus ◽  
Traditional Risk Factors

Abstract Background Chronic kidney disease is a common comorbid condition among persons living with human immunodeficiency virus (PWH). We characterized baseline kidney function in the REPRIEVE (Randomized Trial to Prevent Vascular Events in HIV) trial cohort. Methods REPRIEVE enrolled PWH with low to moderate cardiovascular risk based on traditional risk factors to evaluate the effect of statin therapy on cardiovascular events. We determined baseline estimated glomerular filtration rate (eGFR) with the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), Modification of Diet in Renal Disease, and Cockcroft-Gault equations, and we evaluated baseline factors associated with eGFR <90 mL/min/1.73 m2 by logistic regression. We performed Bland-Altman plots and scatterplots to assess agreement between equations. Results Among 7770 participants enrolled, the median age was 50 years, 31% were female (natal sex), 43% black or African American and 15% Asian, the median body mass index (calculated as calculated as weight in kilograms divided by height in meters squared) was 25.8, and the median CD4 cell count 620/µL. The median CKD-EPI eGFR was 97 mL/min/1.73 m2, and 38% had an eGFR <90 mL/min/1.73 m2. In the adjusted model, factors associated with eGFR <90 mL/min/1.73 m2 included white race, older age, higher body mass index, high-income region of enrollment, hypertension, and tenofovir disoproxil fumarate. The CKD-EPI and Modification of Diet in Renal Disease equations demonstrated strong agreement, particularly at lower eGFR values. Overall, there was 56% concordance between the 3 equations (categories <60, 60 to <90, ≥90 mL/min), improving to 73% after accounting for individual body surface area. Conclusions REPRIEVE enrolled a diverse cohort including a substantial number of PWH with reduced kidney function. Factors associated with reduced eGFR included traditional risk factors and tenofovir disoproxil fumarate exposure. Three commonly used equations have only fair agreement, with potential implications for both clinical care and epidemiologic studies. Clinical Trials Registration NCT02344290.

Stroke in chronic renal failure

2008 ◽  
Vol 149 (15) ◽  
pp. 691-696
Author(s):  
Dániel Bereczki
Keyword(s):  
Risk Factors ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Renal Disease ◽  
Chronic Renal Disease ◽  
Kidney Diseases ◽  
Cerebrovascular Diseases ◽  
Lipid Lowering ◽  
Increased Risk ◽  
Intracerebral Hemorrhages

Chronic kidney diseases and cardiovascular diseases have several common risk factors like hypertension and diabetes. In chronic renal disease stroke risk is several times higher than in the average population. The combination of classical risk factors and those characteristic of chronic kidney disease might explain this increased risk. Among acute cerebrovascular diseases intracerebral hemorrhages are more frequent than in those with normal kidney function. The outcome of stroke is worse in chronic kidney disease. The treatment of stroke (thrombolysis, antiplatelet and anticoagulant treatment, statins, etc.) is an area of clinical research in this patient group. There are no reliable data on the application of thrombolysis in acute stroke in patients with chronic renal disease. Aspirin might be administered. Carefulness, individual considerations and lower doses might be appropriate when using other treatments. The condition of the kidney as well as other associated diseases should be considered during administration of antihypertensive and lipid lowering medications.

scholarly journals Human immunodeficiency virus type 1 gp120 envelope characteristics associated with disease progression differ in family members infected with genetically similar viruses

2013 ◽  
Vol 94 (1) ◽  
pp. 20-29 ◽  
Author(s):  
Elly Baan ◽  
Renée M. van der Sluis ◽  
Margreet E. Bakker ◽  
Vincent Bekker ◽  
Dasja Pajkrt ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Disease Progression ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Positive Charge ◽  
Gp120 Envelope ◽  
Immunodeficiency Virus ◽  
Virus Strains ◽  
Hiv 1

The human immunodeficiency virus type 1 (HIV-1) envelope protein provides the primary contact between the virus and host, and is the main target of the adaptive humoral immune response. The length of gp120 variable loops and the number of N-linked glycosylation events are key determinants for virus infectivity and immune escape, while the V3 loop overall positive charge is known to affect co-receptor tropism. We selected two families in which both parents and two children had been infected with HIV-1 for nearly 10 years, but who demonstrated variable parameters of disease progression. We analysed the gp120 envelope sequence and compared individuals that progressed to those that did not in order to decipher evolutionary alterations that are associated with disease progression when individuals are infected with genetically related virus strains. The analysis of the V3-positive charge demonstrated an association between higher V3-positive charges with disease progression. The ratio between the amino acid length and the number of potential N-linked glycosylation sites was also shown to be associated with disease progression with the healthier family members having a lower ratio. In conclusion in individuals initially infected with genetically linked virus strains the V3-positive charges and N-linked glycosylation are associated with HIV-1 disease progression and follow varied evolutionary paths for individuals with varied disease progression.

scholarly journals The Severity of Diabetic Retinopathy Is an Independent Factor for the Progression of Diabetic Nephropathy

2020 ◽  
Vol 10 (1) ◽  
pp. 3
Author(s):  
Shi-Chue Hsing ◽  
Chia-Cheng Lee ◽  
Chin Lin ◽  
Jiann-Torng Chen ◽  
Yi-Hao Chen ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Diabetic Retinopathy ◽  
Kidney Disease ◽  
Renal Disease ◽  
Disease Progression ◽  
Renal Disease Progression ◽  
Hazard Ratios ◽  
Stage Renal Disease ◽  
End Stage

(1) Background: It has rarely been studied whether the severity of diabetic retinopathy (DR) could influence renal disease progression in end-stage renal disease (ESRD) and chronic kidney disease (CKD) in patients with type 2 diabetes. The aim of this study was to evaluate renal disease progression in ESRD and CKD according to DR severity in patients with type 2 diabetes. (2) Methods: We included 1329 patients and divided the cohort into two end-points. The first was to trace the incidence of ESRD in all enrolled participants and the other was to follow their progression to CKD. (3) Results: Significantly higher crude hazard ratios (HRs) of ESRD incidence in all enrolled participants were noted, and this ratio increased in a stepwise fashion. However, after adjustment, DR severity was not associated with ESRD events. Therefore, a subgroup of 841 patients without CKD was enrolled to track their progression to CKD. Compared with no diabetic retinopathy, the progression of CKD increased in a stepwise fashion, from mild nonproliferative diabetic retinopathy (NPDR) to moderate NPDR, to severe NPDR and to proliferative diabetic retinopathy (PDR), both in the crude and adjusted models. (4) Conclusions: The severity of retinopathy appeared to be associated with renal lesions and the development of CKD. Our findings suggest that the severity of DR is a risk factor for progression to CKD. Therefore, diabetic retinopathy is useful for prognosticating the clinical course of diabetic kidney disease.

scholarly journals Influence of boarding secondary school environment on HIV positive students in South Western Uganda

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Raymond Bernard Kihumuro ◽  
David Jolly Muganzi ◽  
Elton George Wandira ◽  
Racheal Alinaiswe ◽  
Jovitah Joselyne Nanyunja ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Secondary School ◽  
Secondary Schools ◽  
School Environment ◽  
Coping Mechanisms ◽  
Hiv Positive ◽  
Key Informants ◽  
Immunodeficiency Virus ◽  
Negative Coping ◽  
Depth Interviews

Abstract Background The number of human immunodeficiency virus (HIV) positive adolescents in secondary school has increased over the years. Little is known on how the students cope to the pressures and demands of their academic and health lives in the boarding secondary schools. This study explored the factors surrounding their anti-retroviral therapy adherence as well as their experiences. Methods We did a qualitative study that employed in-depth interviews amongst purposively selected 19 HIV positive adolescent students in boarding secondary school and seven key informants. Key informants were members of boarding secondary school staff directly taking care of the adolescents living with human immune virus and had spent at least two academic terms in that school. The study participants were recruited from four health facilities in Bushenyi district, southwestern Uganda, and key informants from five boarding secondary schools in Bushenyi. These were engaged in in-depth interviews using an interview guide. Data was transcribed, coded and the content analyzed thematically. Results Adolescents living with human immunodeficiency virus in boarding secondary school face challenges similar to adolescents outside boarding school settings. However, some challenges are unique to them. Students faced numerous barriers which made it difficult to adhere to their medication. Stigmatization in its different forms was also a major challenge amongst students. Willingness disclosure of serostatus was beneficial to the students since it guaranteed support while at school; facilitating adherence and better living. However, students were uneasy to disclose their status. Some students adopted negative coping mechanisms such as telling lies, escaping from school, and class to access medication. Conclusions Adolescents in boarding secondary schools face similar challenges as compared to their counterparts with some being unique to them. Few school mechanisms help these students to cope while at school. Limited disclosure has proven useful but some adolescents have opted not to disclose their status and hence used negative coping mechanisms. These challenges need to be addressed and a safe environment to encourage limited disclosure should be made.

scholarly journals Interleukin-7-Dependent Production of RANTES That Correlates with Human Immunodeficiency Virus Disease Progression

2003 ◽  
Vol 77 (7) ◽  
pp. 4389-4395 ◽  
Author(s):  
Anuska Llano ◽  
Jordi Barretina ◽  
Arantxa Gutiérrez ◽  
Bonaventura Clotet ◽  
José A. Esté
Keyword(s):  
Human Immunodeficiency Virus ◽  
Disease Progression ◽  
Mononuclear Cells ◽  
Ex Vivo ◽  
Virus Disease ◽  
Chemokine Production ◽  
Interleukin 7 ◽  
Cell Counts ◽  
Immunodeficiency Virus

ABSTRACT There is a relationship between CD4-T-cell number and circulating interleukin 7 (IL-7) levels in human immunodeficiency virus (HIV)-positive individuals. Here, we show that IL-7 induced a dose-dependent production of CCL3 (MIP-1α), CCL4 (MIP-1β), and CCL5 (RANTES) in peripheral blood mononuclear cells (PBMC), ex vivo tonsil lymphoid tissue of HIV− individuals, and PBMC from HIV+ individuals, suggesting that IL-7 may regulate β-chemokine production in vivo. In a cross-sectional study of HIV+ individuals (n = 130), a weak but significant correlation between IL-7 and RANTES was noted (r = 0.379; P < 0.001). Remarkably, the correlation between IL-7 and RANTES increased to an r value of 0.798 (P < 0.001) if individuals with low CD4 cell counts (<200 cells/μl) were excluded from the analysis. Our results suggest that there is a relationship between IL-7 and the production of RANTES both in vitro and in vivo that is lost in immune-compromised patients (CD4 count of <200 cells/μl) but that could be restored by antiretroviral therapy. Unlike the case for IL-7, high levels of RANTES suggest an intermediate stage of HIV disease progression.

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