Epigenetic Associations With Estimated Glomerular Filtration Rate Among Men With Human Immunodeficiency Virus Infection

Abstract Background People living with human immunodeficiency virus (HIV) infection have higher risk for chronic kidney disease (CKD), defined by a reduced estimated glomerular filtration rate (eGFR). Previous studies have implicated epigenetic changes related to CKD; however, the mechanism of HIV-related CKD has not been thoroughly investigated. Methods We conducted an epigenome-wide association study of eGFR among 567 HIV-positive and 117 HIV-negative male participants in the Veterans Aging Cohort Study to identify epigenetic signatures of kidney function. Results By surveying more than 400 000 cytosine guanine dinucleotide (CpG) sites measured from peripheral blood mononuclear cells, we identified 15 sites that were significantly associated with eGFR (false discovery rate Q value < 0.05) among HIV-positive participants. The most significant CpG sites, located at MAD1L1, TSNARE1/BAI1, and LTV1, were all negatively associated with eGFR (cg06329547, P = 5.25 × 10–9; cg23281907, P = 1.37 × 10–8; cg18368637, P = 5.17 × 10–8). We also replicated previously reported eGFR-associated CpG sites including cg17944885 (P = 2.5 × 10–5) located between ZNF788 and ZNF20 on chromosome 19 in the pooled population. Conclusions In this study we uncovered novel epigenetic associations with kidney function among people living with HIV and suggest potential epigenetic mechanisms linked with HIV-related CKD risk.

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Evaluation of Kidney Function Tests in HIV-Positive Patients Receiving Combined Antiretroviral Therapy

10.22541/au.161806151.16736028/v1 ◽

2021 ◽

Author(s):

emre aydın ◽

Fatma Yılmaz Aydın ◽

Yakup Demir ◽

Yaşar Yıldırım ◽

Mustafa Kemal Çelen

Keyword(s):

Human Immunodeficiency Virus ◽

Glomerular Filtration Rate ◽

Antiretroviral Therapy ◽

Filtration Rate ◽

Estimated Glomerular Filtration Rate ◽

Hiv Positive ◽

Group 4 ◽

Immunodeficiency Virus ◽

Combined Antiretroviral Therapy ◽

Group 5

Introduction: Human Immunodeficiency virus is a chronic infection that attacks the immune system of the human body, particularly CD4 T lymphocytes. Combined antiretroviral therapies are highly effective in virological suppression of human immunodeficiency virus infection. It has been shown that some retroviral therapies have a higher nephrotoxicity potential. As a result of renal injury, serum creatinine increases, and the estimated glomerular filtration rate is reduced. The aim of our study was to assess changes in kidney function during a 24-month period in HIV-positive patients who were begun on combined antiretroviral therapy. Material-method: A total of 127 HIV positive patients were enrolled. The patients were divided into five groups; patients who received no therapy were designated as Group 1; those that received Dolutegravir/Abacavir/Lamivudine combination as Group 2; those that received Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide Fumarate combination as Group 3; those that received Emtricitabine/Tenofovir Disoproxil Fumarate/Dolutegravir combination as Group 4; and those that received Emtricitabine/Tenofovir Disoproxil Fumarate/Raltegravir combination as Group 5. We compared the effects of these drugs on estimated glomerular filtration rate during a 24-month follow-up period. Results: At the 24th month of therapy, a significant difference was observed between the eGFR levels of the study groups (p:<0.001). eGFR level was significantly higher in Group 4 compared to Groups 1, 2, and 3 (p:0.009, p:<0.001, p:<0.001, respectively) while it was significantly lower in Group 5 than groups 1, 2, and 3 (p:0.005, p:<0.001, p:<0.001, respectively). No significant eGFR difference was found between Group 4 and Group 5 (p>0.05). Serum creatinine level was significantly higher in Groups 4 and 5 compared to the other groups (p<0.001). Conclusion: The use of TDF-containing regimens causes renal dysfunction. Therefore, we recommend close monitoring of renal function, especially in patients treated with TDF.

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Classification of human immunodeficiency virus-infected patients with chronic kidney disease using a combination of proteinuria and estimated glomerular filtration rate

Clinical and Experimental Nephrology ◽

10.1007/s10157-013-0853-1 ◽

2013 ◽

Vol 18 (4) ◽

pp. 600-605 ◽

Cited By ~ 8

Author(s):

Naoki Yanagisawa ◽

Takashi Muramatsu ◽

Yasuyuki Yamamoto ◽

Ken Tsuchiya ◽

Kosaku Nitta ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Human Immunodeficiency Virus ◽

Glomerular Filtration Rate ◽

Kidney Disease ◽

Glomerular Filtration ◽

Filtration Rate ◽

Estimated Glomerular Filtration Rate ◽

Immunodeficiency Virus

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A Risk Score to Guide Cystatin C Testing to Detect Occult-Reduced Estimated Glomerular Filtration Rate

American Journal of Nephrology ◽

10.1159/000439231 ◽

2015 ◽

Vol 42 (2) ◽

pp. 141-147 ◽

Cited By ~ 3

Author(s):

Carmen A. Peralta ◽

Paul Muntner ◽

Rebecca Scherzer ◽

Suzanne Judd ◽

Mary Cushman ◽

...

Keyword(s):

Glomerular Filtration Rate ◽

Glomerular Filtration ◽

Racial Differences ◽

Kidney Function ◽

Cystatin C ◽

Risk Score ◽

Filtration Rate ◽

Bayesian Model Averaging ◽

Estimated Glomerular Filtration Rate ◽

Risk Function

Background/Aims: Persons with occult-reduced estimated glomerular filtration rate (eGFR <60 ml/min/1.73 m2 detected by serum cystatin C but missed by creatinine) have high risk for complications. Among persons with preserved kidney function by creatinine-based eGFR (eGFRcreat >60 ml/min/1.73 m2), tools to guide cystatin C testing are needed. Methods: We developed a risk score to estimate an individual's probability of reduced eGFR by cystatin C (eGFRcys <60 ml/min/1.73 m2) in The Reasons for Geographic and Racial Differences in Stroke (REGARDS) study and externally validated in the Third National Health and Nutrition Examination Survey (NHANES III). We used logistic regression with Bayesian model averaging and variables available in practice. We assessed performance characteristics using calibration and discrimination measures. Results: Among 24,877 adults with preserved kidney function by creatinine, 13.5% had reduced eGFRcys. Older and Black participants, current smokers and those with higher body mass index, lower eGFRcreat, diabetes, hypertension and history of cardiovascular disease were more likely to have occult-reduced eGFR (p < 0.001). The final risk function had a c-statistic of 0.87 in REGARDS and 0.84 in NHANES. By risk score, 72% of occult-reduced eGFR cases were detected by screening only 22% of participants. Conclusions: A risk score using characteristics readily accessible in clinical practice can identify the majority of persons with reduced eGFRcys, which is missed by creatinine.

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Abstract P526: Bariatric Surgery is Associated With Slower Decline in Kidney Function, Estimated by Multiple Filtration Markers

Circulation ◽

10.1161/circ.141.suppl_1.p526 ◽

2020 ◽

Vol 141 (Suppl_1) ◽

Author(s):

Alex R CHANG ◽

G. C Wood ◽

Adam Cook ◽

Xin Chu ◽

Morgan Grams

Keyword(s):

Bariatric Surgery ◽

Glomerular Filtration Rate ◽

Glomerular Filtration ◽

Kidney Function ◽

Cystatin C ◽

Filtration Rate ◽

Estimated Glomerular Filtration Rate ◽

Morbidly Obese ◽

Surgery Group

Background: Persons with morbid obesity are at increased risk for end-stage kidney disease, and prior studies have shown an association between bariatric surgery and improvements in creatinine-based estimated glomerular filtration rate (eGFR cr ). However, eGFR cr could be biased by loss of muscle mass after surgery, and creatinine-cystatin C estimated glomerular filtration rate (eGFR cr-cyc ) has been shown to be more accurate in this setting. Methods: We matched 144 patients who underwent bariatric surgery on pre-surgery age, sex, race, body mass index (BMI), and eGFR cr with 144 morbidly obese non-surgery patients at Geisinger with serial biobanked serum samples. We measured filtration markers (creatinine, cystatin C, beta-2 microglobulin [B2M] and beta-trace protein [BTP], and calculated eGFR cr-cyc using the CKD-EPI combined equation. Using mixed effects models with random intercepts, we compared changes in filtration markers and eGFR cr-cyc between surgery and non-surgery groups. Results: Mean (SD) values for age, BMI, and eGFR cr were 48.2 (10.4) years, 45.2 (6.3) kg/m 2 , and 91.7 (17.5) ml/min/1.73m 2 ; 87.5% were female, 0.7% were black, 50.3% had hypertension, and 41.0% had type 2 diabetes. Mean eGFR cr-cyc slope in the surgery group was -0.41 ml/min/1.73m 2 /yr (95% CI: -0.74, -0.08) over a mean follow-up of 9.2 (1.4) years, compared to -1.43 ml/min/1.73m 2 /yr in the non-surgery group over a mean follow-up of 8.2 (1.1) years. Bariatric surgery was associated with a 1.02 ml/min/1.73m 2 /yr slower decline in eGFR cr-cyc , and smaller increase in all 4 filtration markers (p< 0.02 for all comparisons). Conclusions: Bariatric surgery is associated with slower decline in kidney function, as assessed by eGFR cr-cyc , B2M and BTP.

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Comparative Effectiveness and Safety of Oral Anticoagulants Across Kidney Function in Patients With Atrial Fibrillation

Circulation Cardiovascular Quality and Outcomes ◽

10.1161/circoutcomes.120.006515 ◽

2020 ◽

Vol 13 (10) ◽

Author(s):

Xiaoxi Yao ◽

Jonathan W. Inselman ◽

Joseph S. Ross ◽

Rima Izem ◽

David J. Graham ◽

...

Keyword(s):

Atrial Fibrillation ◽

Glomerular Filtration Rate ◽

Glomerular Filtration ◽

Kidney Function ◽

Major Bleeding ◽

Comparative Effectiveness ◽

Lower Risk ◽

Filtration Rate ◽

Estimated Glomerular Filtration Rate ◽

Oral Anticoagulants

Background: Patients with atrial fibrillation and severely decreased kidney function were excluded from the pivotal non–vitamin K antagonist oral anticoagulants (NOAC) trials, thereby raising questions about comparative safety and effectiveness in patients with reduced kidney function. The study aimed to compare oral anticoagulants across the range of kidney function in patients with atrial fibrillation. Methods and Results: Using a US administrative claims database with linked laboratory data, 34 569 new users of oral anticoagulants with atrial fibrillation and estimated glomerular filtration rate ≥15 mL/(min·1.73 m 2 ) were identified between October 1, 2010 to November 29, 2017. The proportion of patients using NOACs declined with decreasing kidney function—73.5%, 69.6%, 65.4%, 59.5%, and 45.0% of the patients were prescribed a NOAC in estimated glomerular filtration rate ≥90, 60 to 90, 45 to 60, 30 to 45, 15 to 30 mL/min per 1.73 m 2 groups, respectively. Stabilized inverse probability of treatment weighting was used to balance 4 treatment groups (apixaban, dabigatran, rivaroxaban, and warfarin) on 66 baseline characteristics. In comparison to warfarin, apixaban was associated with a lower risk of stroke (hazard ratio [HR], 0.57 [0.43–0.75]; P <0.001), major bleeding (HR, 0.51 [0.44–0.61]; P <0.001), and mortality (HR, 0.68 [0.56–0.83]; P <0.001); dabigatran was associated with a similar risk of stroke but a lower risk of major bleeding (HR, 0.57 [0.43–0.75]; P <0.001) and mortality (HR, 0.68 [0.48-0.98]; P =0.04); rivaroxaban was associated with a lower risk of stroke (HR, 0.69 [0.51–0.94]; P =0.02), major bleeding (HR, 0.84 [0.72–0.99]; P =0.04), and mortality (HR, 0.73 [0.58–0.91]; P =0.006). There was no significant interaction between treatment and estimated glomerular filtration rate categories for any outcome. When comparing one NOAC to another NOAC, there was no significant difference in mortality, but some differences existed for stroke or major bleeding. No relationship between treatments and falsification end points was found, suggesting no evidence for substantial residual confounding. Conclusions: Relative to warfarin, NOACs are used less frequently as kidney function declines. However, NOACs appears to have similar or better comparative effectiveness and safety across the range of kidney function.

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The use of estimated glomerular filtration rate in the evaluation of renal function in HIV-positive children in Enugu

Annals of Tropical Medicine and Public Health ◽

10.4103/1755-6783.116524 ◽

2013 ◽

Vol 6 (2) ◽

pp. 206 ◽

Cited By ~ 1

Author(s):

BertillaU Ezeonwu ◽

Tagbo Oguonu ◽

HenriettaU Okafor ◽

AnthonyN Ikefuna

Keyword(s):

Renal Function ◽

Glomerular Filtration Rate ◽

Glomerular Filtration ◽

Filtration Rate ◽

Estimated Glomerular Filtration Rate ◽

Hiv Positive

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Relationship Between Metabolic Syndrome Severity and Kidney Function as Related to Gender: A Population-Based Longitudinal Study

Clinical Nursing Research ◽

10.1177/1054773818773385 ◽

2018 ◽

Vol 29 (6) ◽

pp. 355-362 ◽

Cited By ~ 1

Author(s):

Sheng-Pyng Chen ◽

Chi-Rong Li ◽

Huan-Cheng Chang ◽

Yu-Ling Li ◽

Hsiang-Chu Pai

Keyword(s):

Metabolic Syndrome ◽

Glomerular Filtration Rate ◽

Glomerular Filtration ◽

Kidney Function ◽

Filtration Rate ◽

Estimated Glomerular Filtration Rate ◽

Population Based ◽

Health Examination ◽

Z Score ◽

The Metabolic Syndrome

The purpose of this study was to explore the relationship between the metabolic syndrome severity Z-score and kidney function by gender. We also examined the estimated glomerular filtration rate in relation to other known risk factors. The study used was a population-based prospective longitudinal research design. A total of 4,838 participants (2,683 females and 2,155 males) included individuals aged >30 years who were undergoing a health examination from 2006 to 2014 in Pingzhen City, Taiwan. In the initial generalized estimated equation model analysis, which included the covariates of age of first visit, period between the first and current visit, and metabolic syndrome severity Z-score, the results indicated that the interaction between age and metabolic syndrome severity Z-score is significantly related to the estimated glomerular filtration rate for males ( p = .040). For females, the interaction between age and metabolic syndrome severity Z-score was not significant, but a higher metabolic syndrome severity Z-score was significantly associated with lower estimated glomerular filtration rate ( p = .001). After controlling for the confounders, unhealthy behaviors, and comorbidities, the metabolic syndrome severity Z-score was still a negative predictor of estimated glomerular filtration rate in both the male ( p = .005) and female ( p = .023) models.

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