Saleem Bharmal9/23/08

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