Effect of Pitavastatin on Kidney Function in HIV-infected Persons

Project: Research project

Project Details

Description

OBJECTIVES

OBJECTIVE 1: To evaluate the effects of pitavastatin on clinically relevant parameters of kidney function among HIV-infected individuals on ART.

OBJECTIVE 1A: To determine whether pitavastatin is associated with a lower incidence of clinically relevant eGFR decline in HIV-infected persons.

OBJECTIVE 1B: To determine whether pitavastatin is associated with a lower prevalence of albuminuria.

HYPOTHESES: 1. We hypothesize that randomization to pitavastatin versus placebo will be associated with a lower incidence of clinically relevant eGFR decline, defined as ≥30% decline from baseline, a Food and Drug Administration/National Kidney Foundation (FDA/NKA) recommended surrogate endpoint for CKD [Inker 2014]. 2. We hypothesize that randomization to pitavastatin versus placebo will be associated with a lower prevalence of albuminuria, defined as urine albumin/creatinine ratio (ACR) >30 mg/g.

OBJECTIVE 2: To assess whether the effect of pitavastatin 4 mg/daily on eGFR and albuminuria is stronger in high-risk groups defined by older age, black race, hypertension, lower CD4 cell counts, or the use of tenofovir-containing regimens.

HYPOTHESIS: We hypothesize the kidney protective effect of pitavastatin will be stronger in high-risk groups.

OBJECTIVE 3: To determine whether the effect of pitavastatin on kidney function is mediated through anti-inflammatory effects.

HYPOTHESIS: We hypothesize that effects of pitavastatin on eGFR and albuminuria will be mediated by systemic and vascular inflammation and oxidative stress, as measured by circulating levels of key inflammatory biomarkers.

SIGNIFICANCE

By adding collection of urine and blood longitudinally in at least 2500 participants, this ancillary study will definitively assess whether pitavastatin therapy will prevent significant decline in kidney function and the development of albuminuria (ACR >30 mg/g). This sample will further provide the opportunity to evaluate the effect of pitavastatin in sub-groups of HIV-infected participants for whom the risk of CKD has been demonstrated to be higher, including persons of older age, black race, hypertension, lower CD4 T-cell counts, and on tenofovir-containing regimens. Finally, the mechanisms of action will be assessed to determine whether the protective effect of pitavastatin is mediated through pathways involving inflammation and oxidative stress. Ultimately, the findings of this study will provide longitudinal data on the epidemiology of CKD in the setting of HIV infection, provide mechanistic insights into whether statins prevent CKD by modulating inflammation and oxidative stress, and potentially change guidelines for the prevention of CKD in this at-risk population.
StatusFinished
Effective start/end date7/1/166/30/18

Funding

  • Brigham and Womens Hospital (UAB FUND#114959//R01DK108438-02)
  • National Institute of Diabetes and Digestive and Kidney Diseases (UAB FUND#114959//R01DK108438-02)

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