The overall goal of this application is to support the education and clinical research of the investigator leading to an independent career in patient-oriented research focused on HIV-related kidney disease. With the career development award and a program of didactic and scientific training, the goals will be achieved by: 1) receiving direct mentorship in study methods, statistical analysis, scientific communication and manuscript preparation 2) obtaining formal instruction in the Graduate Training Program in Clinical Investigation and advanced courses in cohort design/ statistical analysis and genetic epidemiology and 3) implementing the research proposal with guidance and input from mentors and collaborators in the supportive environment offered by the Johns Hopkins Schools of Medicine and Public Health, and the Welch Center for Prevention, Epidemiology and Clinical Research. Survival of HIV-infected individuals has improved significantly with highly active antiretroviral therapy (HAART);consequently, chronic illnesses such as kidney disease are of increasing concern. The overall aim of the proposal is to quantify the burden of chronic kidney disease (CKD) in HIV-infected individuals using serum creatinine and cystatin C and to investigate whether HIV- and host-related factors are involved in the development and progression of CKD in HIV-positive individuals. This proposal will use two unique study populations: 1) a large, racially diverse population of HIV-positive individuals with extended follow-up from the Multicenter AIDS Cohort Study (MACS) and the Womens'Interagency HIV Study (WIHS) cohorts;and 2) a clinic-based study population of HIV-positive individuals recruited through the Johns Hopkins HIV/AIDS Service. This proposal will provide: 1) the current epidemiology of HIV-related CKD in the U.S. and its impact on mortality;2) a comparison of the prevalence of CKD based on cystatin C versus serum creatinine estimates of kidney function;3) an investigation of the risk of CKD development and progression related to HAART and HIV disease stage;and 4) a validation of the association of MYH9 with CKD progression and specific renal histopathologic findings.

Public Health Relevance

This proposal will have important implications in screening and identifying CKD in this high risk population. It will determine the impact of CKD in the natural history of HIV infection and determine risk factors for CKD during the HAART era. It will yield a potential mechanism for HIV-related CKD which may ultimately lead to the development of diagnostic and prognostic markers for HIV-related CKD.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
5K23DK081317-04
Application #
8298633
Study Section
Diabetes, Endocrinology and Metabolic Diseases B Subcommittee (DDK)
Program Officer
Rankin, Tracy L
Project Start
2009-07-01
Project End
2014-06-30
Budget Start
2012-07-01
Budget End
2013-06-30
Support Year
4
Fiscal Year
2012
Total Cost
$153,487
Indirect Cost
$11,369
Name
Johns Hopkins University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Kim, Julie E; Scherzer, Rebecca; Estrella, Michelle M et al. (2016) Tenofovir exposure alters associations of serum bicarbonate with chronic kidney disease risk in HIV-infected veterans. AIDS 30:1049-57
Zachor, Hadas; Machekano, Rhoderick; Estrella, Michelle M et al. (2016) Incidence of stage 3 chronic kidney disease and progression on tenofovir-based regimens. AIDS 30:1221-8
Abraham, Alison G; Althoff, Keri N; Jing, Yuezhou et al. (2015) End-stage renal disease among HIV-infected adults in North America. Clin Infect Dis 60:941-9
Chen, Teresa K; Choi, Michael J; Kao, W H Linda et al. (2015) Examination of Potential Modifiers of the Association of APOL1 Alleles with CKD Progression. Clin J Am Soc Nephrol 10:2128-35
Jotwani, Vasantha; Scherzer, Rebecca; Abraham, Alison et al. (2015) Association of urine α1-microglobulin with kidney function decline and mortality in HIV-infected women. Clin J Am Soc Nephrol 10:63-73
Chen, Teresa K; Estrella, Michelle M; Astor, Brad C et al. (2015) Longitudinal changes in hematocrit in hypertensive chronic kidney disease: results from the African-American Study of Kidney Disease and Hypertension (AASK). Nephrol Dial Transplant 30:1329-35
Jotwani, Vasantha; Shlipak, Michael G; Scherzer, Rebecca et al. (2015) APOL1 Genotype and Glomerular and Tubular Kidney Injury in Women With HIV. Am J Kidney Dis 65:889-98
Foy, Matthew; Sperati, C John; Lucas, Gregory M et al. (2014) Drug interactions and antiretroviral drug monitoring. Curr HIV/AIDS Rep 11:212-22
Ng, Derek K; Jacobson, Lisa P; Brown, Todd T et al. (2014) HIV therapy, metabolic and cardiovascular health are associated with glomerular hyperfiltration among men with and without HIV infection. AIDS 28:377-86
Estrella, Michelle M; Moosa, Mohammed R; Nachega, Jean B (2014) Editorial commentary: Risks and benefits of tenofovir in the context of kidney dysfunction in sub-Saharan Africa. Clin Infect Dis 58:1481-3

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