Dr Kibaru

HIV-ASSOCIATED
NEPHROPATHY (HIVAN)
 Renal disease a relatively
common complication in patients
with HIV
objectives
At the end of the session,the students
should be able to
◦ Discuss the relationship between HIV and
renal disease
◦ Define HIVAN
◦ Describe the clinical presentation,
investigations and treatment of HIVAN
 Renal disease can result from
1. Direct kidney infection with HIV
2. Drugs—ART,drugs used in treatment of
opportunistic infections
3. Prerenal azotemia due to volume depletion due to
poor nutrition,nausea and vomiting
 HIVAN defined
Classically a pentad
◦ Proteinuria
◦ Azotemia
◦ Normotension
◦ Normal to large kidneys on u/s
◦ Focal and segmental glomerulosclerosis

It is an important consideration in HIV sero-positive

and have proteinuria
 Epidemiology

Occurs in 2 to 10 % of HIV infected patients

Can occur in all risk groups,including children
with perinatal infection

M:F ratio is 10:1, uncommon in homosexuals

Predilection for blacks – An interaction
between genetic factors and HIV appear
to be important in development of
nephropathy

The3rd leading cause of ESRD in black

Americans btn 20 – 64 yrs
 Pathogenesis
Complex and incompletely understood
Using transgenic murine models -a direct role
of HIV type 1 (HIV-1) in the development of
HIVAN.
A genetic or environmental cofactor that has
not yet been identified
Target is the renal glomerular and tubular
epithelium
 Pathogenesis (cont)
Role of cytokines
◦ cytokines are upregulated by viral proteins e.g.
gp 120.
◦ Inflammatory i.e. IL-6,IL-1, IL10, TNF-alpha,
◦ Fibrogenic i.e. TGF-beta, fibroblast growth factor
TGF-beta
◦ associated with mesangial proliferation and
mesangial matrix expansion
◦ can produce fibrosis, tubular damage, glomerular
collapse, interstitial edema and rapid renal damage
and failure.
 Presentation
A nephrotic syndrome consisting of
◦ nephrotic range proteinuria
◦ Hypertension not common
◦ Hematuria, micro > macro
◦ Varying degrees of azotemia – normal renal function at
presentation uncommon
HIV disease usually advanced with low
CD4 counts (adults < 200 cells/ul),but it
has been reported in patients with higher
CD4 counts

Usuallyfollows a progressive course with

ESRD frequently developing within 4 to
12 months
 Investigations
Urinalysis – microhematuria,leucocytes,hyaline
casts,no cellular casts
-- Nephrotic range proteinuria
Renal fxn tests
Serum total proteins and albumin
Serum complement levels – usually normal

Renal ultrasound – Normal to large and

hyperechogenic kidneys.

◦ May be due to prominent interstitial expansion by cellular infiltrate and

markedly dilated tubules containing voluminous casts
 Biopsy
Controversial
Classic presentation is predictive of
biopsy diagnosis in 55 to 60% only

Biopsy may be needed to distinguish

HIVAN from other forms of renal
disease
 Histopathology
Light microscopy
◦ Commonest lesion is a collapsing form of
FSGS (present in 80-90% of patients)
◦ mesangial hyperplasia
◦ Segmental necrotising glomerulonephritis
◦ Minimal change disease
Immunoflourescence - albumin and IgG on
epithelial cells; and IgM, C3 + IgA on
mesangial cells and sclerotic areas.
 Electron microscopy
Wrinkling and collapse of glomerular basement
membrane,
Epithelial cell proliferation
Focal detachment and effacement of the epithelial
foot processes
Accumulation of mesangial matrix in
sclerosed glomeruli
Abundance of tubuloreticular inclusions
in endothelial cells consisting of
ribonucleoprotein and membrane which
are stimulated by alpha interferon highly
predictive of HIVAN
 Goals in treatment of HIVAN
• Minimize viral load to prevent renal cell
infection
• Minimize cytokine-mediated renal injury

• Eliminate cells infiltrating the interstitium,

reducing further renal damage

• Minimize protein loss

Treatment
Symptomatic treatment of edema includes low salt
diet and diuretics.
HAART has improved survival and slows progression
to ESRD in patients with HIVAN.
Incidence of HIVAN reported to be
declining since the introduction of
HAART.
Treatment with corticosteroids may
reduce progression to ESRD though
serious infectious complications may
result.

Cyclosporine may help in the steroid

resistant cases
 Treatment (cont)
ACE-I reduce intraglomerular pressure, proteinuria,
and possibly modulate cytokine-mediated renal
injury
Renal replacement therapy,in form of haemodialysis
or peritoneal dialysis, used in HIVAN patients who
progress to ESRD.
There is high risk of sepsis in peritoneal
dialysis.
Kidney transplantation – risk of
opportunistic infections with post
transplantation immunosuppression
 REFERENCES
 Berhman,Kliegman, Jenson.Nelsons Textbook of Pediatrics. 18TH Ed, Pg 1115
 Fauci,Braunwald..,Harrison’s Principles of Internal Medicine
 Roxana M, Bologa Md. The AIDS Reader 9(1):38-42,1999
 Han TM Et Al. A Cross-sectional Study of Hiv-seropositive Patients With Varying
Degrees of Proteinuria in South Africa.Kidney Int. 2006 May 3
 Tanji N Et Al. Detection and Localization of HIV-1 DNA in Renal Tissues by in Situ
Polymerase Chain Reaction. Histol Histopathol. 2006 Apr;21(4):393-401
 Behar Et Al. Absence of Hiv-associated Nephropathy in Ethiopians.Am J Kidney Dis.
2006 Jan;47(1):88-94.
 Pope Sd Et Al. Pharmacotherapy for Human Immunodeficiency Virus-associated
Nephropathy.Pharmacotherapy. 2005 Dec;25(12):1761-72.
 Tang B Et Al. Fibroblast Growth Factor-2 Increases the Renal Recruitment and
Attachment of Hiv-infected Mononuclear Cells to Renal Tubular Epithelial
Cells.Paediatr Nephrol. 2005 Dec;20(12):1708-16.
 Kumar Ms Et Al. Safety and Success of Kidney Transplantation and Concomitant
Immunosuppression in Hiv-positive Patients. Kidney Int. 2005 Apr;67(4):1622-9.
 Moro Salifu, Sidhartha Pani. HIV Nephropathy. Emedicine, Updated December 14
2004.