More than 1.1 million people in the United States (US) are living with human immunodeficiency virus (HIV) infection, and an estimated 30% of people living with HIV (PLWH) have evidence of chronic kidney disease (CKD). Compared to the general population, the rate of end-stage renal disease (ESRD) among PLWH is tenfold greater and mortality on dialysis is 19-fold higher. Contributors to CKD in PLWH include comorbidities shared with the uninfected population, HIV-specific factors, and genetic variants; however, the interplay of these various determinants remains incompletely understood. Existing CKD risk prediction tools for PLWH have low sensitivity and insufficient positive predictive value for clinical decision-making. The ability to risk- stratify PLWH and distinguish those at highest risk for future development of CKD from those at low risk is critical to optimize care and patient outcomes. PLWH at high risk can be targeted for interventions to slow CKD progression and improve survival, including earlier establishment of nephrology care and referral for transplantation; while identification of those at low risk allows for the development of a living donor selection framework specific to PLWH, effectively expanding HIV+ to HIV+ transplantation to include living donors. We hypothesize that the impact of HIV on CKD risk varies by the interplay between comorbid conditions, HIV- related factors, and genetic variants, and distinct phenotypes of PLWH with high and low CKD risk exist. To better understand this relationship, we will leverage the Centers for AIDS Research Network of Integrated Clinical Systems (CNICS), a unique prospective clinical cohort with > 32,000 participants, and will address the following unique aims: (1) to explore the association of clinical characteristics with risk for CKD; (2) to explore the association of genetic variants with risk for CKD and correlate histologic findings with genetic risk; and (3) develop a tool for predicting CKD risk among PLWH. Stratification by risk for future development of CKD is critical for identifying those PLWH at highest risk that would benefit from early nephrology care and referral for transplantation and those at lowest risk that could be eligible for living kidney donation. Using an existing cohort of PLWH representative of the US HIV population to inform CKD risk prediction is necessary, practical, and novel. Our findings will contribute new insights into the relationship between HIV and risk for kidney disease.

Public Health Relevance

More than 1.1 million people in the United States (US) are living with human immunodeficiency virus (HIV) infection, and an estimated 30% of people living with HIV (PLWH) have evidence of chronic kidney disease (CKD). Compared to the general population, the rate of end-stage renal disease among PLWH is tenfold greater and mortality on dialysis is 19-fold higher. With the observed high rates of mortality on dialysis, the ability to risk stratify PLWH by risk for future development of CKD is critical for identifying those at highest risk who would benefit from early referral for nephrology care and transplant evaluation and lowest risk who could be eligible living kidney donors for PLWH in need of transplant.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
1R01DK117675-01
Application #
9554567
Study Section
AIDS Clinical Studies and Epidemiology Study Section (ACE)
Program Officer
Kimmel, Paul
Project Start
2018-09-01
Project End
2019-08-31
Budget Start
2018-09-01
Budget End
2019-08-31
Support Year
1
Fiscal Year
2018
Total Cost
Indirect Cost
Name
University of Alabama Birmingham
Department
Surgery
Type
Schools of Medicine
DUNS #
063690705
City
Birmingham
State
AL
Country
United States
Zip Code
35294