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Saleem Bharmal

9/23/08
Association between HIV and renal disease
first reported in 1984

HIV-1 seropositive patients

Renal syndrome characterized by progressive
renal failure and proteinuria

Most common kidney biopsy finding was
FSGS
HIV-1 seropositive
Low CD4 counts (< 250) and/or other criteria
for AIDS
Proteinuria, often in the nephrotic range
Most patients have moderate to severe renal
insufficiency at the time of diagnosis
Peripheral edema is uncommon
Hypertension is rare
Renal ultrasound shows echogenic kidneys
that are normal-to-large in size
Collapsing form of Focal segmental
glomerulosclerosis (FSGS)

Microcystic dilatation or renal tubules

Globally sclerotic glomeruli

Lymphocytic interstitial infiltrates and Interstitial
fibrosis

Podocyte proliferation and loss of podocyte
differentiation markers

Endothelial tubuloreticular inclusions seen on EM


Only 40-50% are confirmed to be HIVAN by
renal biopsy in suspected cases
Alternative findings include:

MPGN (Hep C) MN (Hep B)
IgA nephropathy Diabetic nephropathy
Amyloidosis AIN
Cryoglobulinemia MCD



Effects mainly black and hispanic patients

In the US, black patients with HIV-1 are 12
times more likely to develop HIVAN than non-
black patients.

Now the third leading cause of ESRD in
African Americans between age 20 and 64

Marked racial disparity suggests genetic
factors are important determinants of HIVAN

Mice transgenic for replication defective HIV-
1 construct lacking gag/pol genes developed
proteinuria, renal failure, and histologic
disease identical to HIVAN

Nephropathy developed in kidney
transplanted from transgenic mice into wild
type, but not in kidneys from normal wild
type transplanted into transgenic mice


Bruggeman et al. reported a series of 20 HIV-1
seropostive pts with renal disease who
underwent renal biopsy

15 of the 20 pts had HIVAN confirmed by biopsy

In 11 of the 15 pts with HIVAN, HIV-1 was
detectable in renal epithelial cells by RNA in situ
hybridization

HIV-1 RNA was detected in renal tubular
epithelial cells, glomerular visceral and parietal
epithelial cells, and interstitial leukocytes
Bruggeman et al. later detected HIV-1in renal
cells by both RNA in situ hybridization and
DNA in situ PCR in 3 patients with
undetectable viral loads

Case repot by Winston et al. described a pt
who developed HIVAN with acute HIV-1
seroconversion that imporved with HAART
however the pt continued to express HIV-1 in
renal epithelial cells
Consists of 9 genes that encode fifteen protein


Podocytes are normally terminally
differentiated, quiescent cells that do not
proliferate
The collapsing glomerulopathy of HIVAN is
characterized by marked podocyte
dedifferentiation and proliferation
Husain et al. showed that nef in vitro is
necessary to cause most of the podocyte
changes seen in HIVAN

HIV-1-associated nephropathy incidence stratified by
AIDS status and antiretroviral use. White bars, no
antiretroviral therapy; light grey bars, nucleoside reverse
transcriptase inhibitor therapy; dark gray bars, highly
active antiretroviral therapy.
The incidence of HIV-1-associated nephropathy by calendar
period and AIDS status.
Lucas: AIDS, Volume 18(3).February 20,
2004.541-546

ACE Inhibitors Small studies have shown
benefit in patients who have been put on ACEI
complared to those who were not on ACEI
with decrease in proteinuria and decrease
rate of renal dysfunction

? Prednisone Only a few small retrospective
cohort studies have shown decrease in serum
Cre and prtoeinuria after treatment with
prednisone