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Clinical Research: Susceptibility of HIV positive individuals to HIVAN is influenced by Genetic variations in podocyte genes in the presence of additional environmental insults

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Name: Glendah Kalunga image kalunga

Hospital / Affiliation:
Charlotte Maxeke Johannesburg Academic Hospital / University of The Witwayersrand

Home Country: Zambia

Host Country: South Africa

Year: 2012

Status of your program: IN PROGRESS

 

Title of the project: 

Susceptibility of HIV positive individuals to HIVAN is influenced by Genetic variations
in podocyte genes in the presence of additional environmental insults

Topic: 

Chronic Kidney Disease

 

Short description of the project or abstract:

The prevalence of HIV-CKD in South Africa is 6%. Kidney disease is a common complication of HIV infection. The past literature has shown that 50-60% are considered classic HIV-associated nephropathy (HIVAN). However, recent studies show downward trends in HIVAN occurrence. In South Africa, one study showed that HIVAN (27%) and HIVICK (21%), and the other HIVAN was the commonest diagnosis. However, there were limitations to these studies. We conducted a prospective study looking at the clinical and histological profile and genetic susceptibility as well as environmental factors that influence the development of HIV kidney disease and compared this to HIV negative individuals. Participants have been recruited at 3 public hospitals in Johannesburg. Every patient presenting to renal and HIV clinics was given the opportunity to participate following informed consent. Patients with proteinuria were followed up for CKD. The patients were stratified into 5 groups; HIVAN, non-HIVAN CKD, HIV-negative CKD, HIV positive and HIV negative without kidney disease. Kidney biopsies were done for histological diagnosis. We have followed up these patients over a period of 3 years and are analysing disease progression over this period of time. 371 patients have been recruited.

A descriptive analysis has been conducted using STATA 13, looking at characteristics, risk factors and associations. Our study has described a variety of renal pathology in both HAART experienced and HAART naïve and HIV negative patients. Our study has so far shown no statistical differences noted in the occurrence of common histological patterns amongst the HIV positive and negative populations, except for FSGS and MCD. There appears to be a shift in the prevalence of HIVAN as evidenced by low numbers. HAART initiation does not appear to promote HIVICK over HIVAN. Literature has suggested that this is due to early initiation of HAART, which modifies the immune status and enhances immune complex GNs (HIVICK). This is not the case in our cohort. Our analysis is ongoing and we are exploring the reasons for this. We are looking into questions relating to the dynamics of inadequate viral suppression, the natural evolution of the HIV virus and infection and genetic adaptation. We are currently genotyping for APOL 1 risk variants and assessing the contribution of environmental factors namely CMV, Mycoplasma, JC polyomavirus and BK virus and the role these all play in determining the histological pattern of the HIV kidney disease. We will further explore the role of the Nef and vpr HIV gene proteins in the pathogenesis of HIVAN. It is hoped that at the end of our study, we will add knowledges on the pathogenesis of HIVAN.

 

Learning or Research objectives:

  • To demonstrate that APOL 1 gene risk variants underlie the genetic susceptibility to HIVAN in a Southern African population
  • To determine whether renal infection by CMV, Mycoplasma, JC polyoma and BK viruses participates in the pathogenesis of HIVAN
  • To determine whether variations of Nef and vpr HIV gene proteins contribute to the histological pattern of HIV kidney disease in South Africa

 

Additional Info

  • Year: 2012
  • Status: In progress
  • Partners: ISN only
  • Region: Africa
  • Country: Zambia
  • Topics: CKD
Read 6815 times Last modified on Saturday, 07 May 2016 18:11

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