• Login
    View Item 
    •   ResearchSpace Home
    • College of Health Sciences
    • School of Laboratory Medicine & Medical Sciences
    • Optics and Imaging
    • Doctoral Degrees (Optics and Imaging)
    • View Item
    •   ResearchSpace Home
    • College of Health Sciences
    • School of Laboratory Medicine & Medical Sciences
    • Optics and Imaging
    • Doctoral Degrees (Optics and Imaging)
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    The spectrum of HIV related nephropathy in KwaZulu-Natal : a pathogenetic appraisal and impact of HAART.

    Thumbnail
    View/Open
    Ramsuran_Duran_2012.pdf (14.10Mb)
    Date
    2012
    Author
    Ramsuran, Duran.
    Metadata
    Show full item record
    Abstract
    Sub-Saharan Africa bears 70% of the global HIV burden with KwaZulu-Natal (KZN) identified as the epicenter of this pandemic. HIV related nephropathy (HIVRN) exceeds any other causes of kidney diseases responsible for end stage renal disease, and has been increasingly recognized as a significant cause of morbidity and mortality. There is nonetheless a general lack of surveillance and reporting for HIVRN exists in this geographical region. Consequentially, the aim of this study was to outline the histopathogical spectrum of HIVRN within KZN. Moreover, from a pathology standpoint, it is important to address whether HIVRN was a direct consequence of viral infection of the renal parenchyma or is it a secondary consequence of systemic infection. Additionally, an evaluation of the efficacy of Highly Active Anti-Retroviral Therapy (HAART) in combination with angiotensin converting enzyme inhibitors (ACE-I) was performed via a genetic appraisal of localized replication of HIV-1 in the kidney, ultrastructural review and immunocytochemical expression of a podocyte maturity and proliferation marker pre and post-HAART. Blood and renal biopsies were obtained from 30 children with HIV related nephropathy pre- HAART, followed-up clinically for a period of 1 year. This cohort formed the post-HAART group. Clinical and demographic data were collated and histopathology, RT-PCR, sequencing, immunocytochemistry and transmission electron microscopy was performed. The commonest histopathological form of HIVRN in children (n = 30) in KZN was classical focal segmental glomerular sclerosis (FSGS) presented in 13(43.33%); mesangial hypercellularity 10(30%); mesangial, HIV associated nephropathy 3(11%) and minimal change disease 2(6.67%). Post-HAART (n = 9) the predominant pathology was mesangial hypercellularity 5(55.56%); FSGS 3(33.33%) and sclerosing glomerulopathy 1(11.11%). This study also provides data on the efficacy of HAART combined with ACE-I. The immunostaining pattern of synaptopodin, Ki67 and p24 within the glomerulus expressed as a mean field area percentage was significantly downregulated in the pre-HAART compared to the post-HAART group respectively (1.14 vs. 4.47%, p = 0.0068; 1.01 vs.4.68, p < 0.001; 4.5% vs 1.4%, p = 0.0035). The ultrastructural assessment of all biopsies conformed to their pathological appraisal however, features consistent with viral insult were observed. Latent HIV reservoirs were observed within the podocyte cytoplasm but was absent in mesangial or endothelial cells. Real-Time polymerase chain reaction assays provided evidence of HIV-1 within the kidney. Sequence analysis of the C2-C5 region of HIV-1 env revealed viral diversity between renal tissue to blood. In contrast to a collapsing type of FSGS that occurs in adults, the spectrum of paediatric nephropathy in treatment-naive children within KwaZulu-Natal was FSGS with mesangial hypercellularity. Additionally, our study demonstrates podocyte phenotype dysregulation pre- HAART and reconstitution post therapy. Evidence of ultrastructural viral reservoirs within epithelial cells is supported by a genetic appraisal confirming the ubiquitous presence of HIV DNA in renal tissue. Moreover, sequence analysis showed viral evolution and compartmentalization between renal viral reservoirs to blood. Finally, the interplay of viral genes and host response, influenced by genetic background, may contribute to the variable manifestations of HIV-1 infection in the kidney in our paediatric population.
    URI
    http://hdl.handle.net/10413/10447
    Collections
    • Doctoral Degrees (Optics and Imaging) [7]

    DSpace software copyright © 2002-2013  Duraspace
    Contact Us | Send Feedback
    Theme by 
    @mire NV
     

     

    Browse

    All of ResearchSpaceCommunities & CollectionsBy Issue DateAuthorsTitlesSubjectsAdvisorsTypeThis CollectionBy Issue DateAuthorsTitlesSubjectsAdvisorsType

    My Account

    LoginRegister

    DSpace software copyright © 2002-2013  Duraspace
    Contact Us | Send Feedback
    Theme by 
    @mire NV