Saleem Bharmal
9/23/08
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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
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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
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Collapsing form of Focal segmental
glomerulosclerosis (FSGS)
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Microcystic dilatation or renal tubules
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Globally sclerotic glomeruli
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Lymphocytic interstitial infiltrates and Interstitial
fibrosis
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Podocyte proliferation and loss of podocyte
differentiation markers
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Endothelial tubuloreticular inclusions seen on EM
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Only 40-50% are confirmed to be HIVAN by
renal biopsy in suspected cases
Alternative findings include:
MPGN (Hep C)
IgA nephropathy
Amyloidosis
Cryoglobulinemia
MN (Hep B)
Diabetic nephropathy
AIN
MCD
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Effects mainly black and hispanic patients
In the US, black patients with HIV-1 are 12
times more likely to develop HIVAN than nonblack patients.
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Now the third leading cause of ESRD in
African Americans between age 20 and 64
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Marked racial disparity suggests genetic
factors are important determinants of HIVAN
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Mice transgenic for replication defective HIV1 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
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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
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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
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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
The incidence of HIV-1-associated nephropathy by calendar
period and AIDS status.
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.
Lucas: AIDS, Volume 18(3).February 20,
2004.541-546
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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