Project: Proximal tubular renal dysfunction among HIV patients on Tenofovir versus Tenofovir sparing regimen

Acronym	TREND Study (Reference Number: TMA 2015 CDF - 1002)
Duration	01/05/2017 - 30/04/2019
Project Topic	Background: Tenofovir Disoproxil Fumarate (TDF) is the most widely used Antiretroviral drug due to its antiviral potency, safety profile and tolerability. TDF causes proximal tubular renal dysfunction (PTRD) leading to Fanconi syndrome, acute kidney injury and chronic kidney damage. TDF induced renal toxicity can be missed because it is initially subclinical and manifests as PTRD. Studies investigating TDF toxicity using estimated Glomerular Filtration Rate (GFR) report only 2-4% prevalence while studies investigating PTRD report up to 22% prevalence. PTRD is determined through urinalysis for glucose and tubular proteinuria, serum phosphate & bone fracture rate. Objectives: The TREND study will compare PTRD among HIV infected patients on a TDF regimen and patients on TDF sparing regimen and compare the estimated GFR among HIV infected patients on TDF regimen and patients on TDF sparing regimen. This study will also assess the determinants of the association between PTRD and TDF use in HIV infected patients and determine sensitivity and specificity of normoglycemic glucosuria in assessing proximal tubular renal dysfunction in HIV patients on ART. Methods: This will be a cross sectional analytic study of HIV infected patients attending Academic Model Providing Access to Healthcare (AMPATH) program in Western Kenya. Laboratory tests will be carried out to determine the outcomes of interest. Primary outcome of interest for this study is PTRD while the secondary outcome of interest is estimated GFR. PTRD will be defined as any two of beta 2 microglobulin in urine, normoglycemic glucosuria and phosphate wasting. Data will be analysed using Stata version 15. Univariate descriptive and inferential analysis will be done. Multivariate analysis will be carried out using logistic regression analysis. Sensitivity and specificity for glucosuria will be calculated compared to PTRD as the reference. Student t test, chi square and likelihood ratio will be used to determine statistical significance. Ethical approval will be sought from the local ethics committee and AMPATH and hospital administration. EDCTP scope: The TREND study will promote the career development of the investigator who is a postgraduate medical researcher in Western Kenya to attain a Master of Medicine degree and earn skills in research. Expected impact: There is limited data on TDF induced PTRD among African patients and lack of proper guidelines on lab monitoring. This study will add new knowledge on subclinical tubular injury and improve monitoring guidelines as well as validate use of simper markers for detection of PTRD.
Network	EDCTP2
Call	Training and Mobility Awards: Career Development Fellowships

Project partner

Number	Name	Role	Country
1	Moi University	Coordinator	Kenya