HIV Associated Nephropathy (HIVAN)

The prevalence of acute kidney injury among HIV patients is higher as compared to the general healthy population. HIV associated nephropathy (HIVAN) more common among HIV positive patients who are not on antiretroviral therapy as compared to the ones who are compliant with antiretroviral therapy.

It is most commonly seen in persons who are newly diagnosed with late-stage HIV infection or in those who have discontinued antiretroviral therapy, and it may present as acute kidney injury or chronic kidney disease.

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In addition to HIVAN, the spectrum of HIV-associated kidney disease includes HIV immune complex kidney disease (HIVICK) and thrombotic microangiopathy.

HIVAN is classically associated with rapid progression to end-stage renal disease (ESRD) and it occurs in advanced HIV disease. Epidemiologically HIVAN is observed almost exclusively in persons of African descent, who account for approximately 90% of HIVAN-related cases of ESRD.

HIVAN has distinct histology, representing a collapsing form of focal segmental glomerulosclerosis (FSGS).

The pathogenesis of HIVAN requires local HIV infection of the kidney, with the virus infecting tubular and glomerular epithelial cells. Along with local infection of the kidney, systemic HIV infection and systemic immune dysfunction may also contribute to disease pathogenesis.

The strong racial disparity in HIVAN and associated ESRD is related to polymorphisms in the APOL1 gene, a gene on chromosome 22 that encodes apolipoprotein 1 and is associated with susceptibility to trypanosomiasis.

The recommended initial treatment for HIVAN is Antiretroviral and there is some evidence of benefit with adjunctive therapies including angiotensin-converting enzyme inhibitors ie captopril or angiotensin receptor blockers and corticosteroids. Most experts would limit the use of corticosteroids ie prednisone to patients with progressive disease despite antiretroviral therapy.

Although combined ART is effective at preventing and reversing HIVAN, long-term use of such therapy has been linked to increased risk for focal segmental glomerulosclerosis, arterionephrosclerosis, and diabetic nephropathy.

Pathologic classification of HIV related kidney diseases

HIV-related kidney diseases fall under four pathologic classifications:

Glomerular-dominant nephropathies:

HIV associated nephropathy and

Immune complex-mediated glomerular diseases.

Tubulointerstitial-dominant nephropathies: 

HIV associated nephropathy-related tubulointerstitial injury;

ART-induced acute tubular injury;

Drug-induced (other than ART) tubulointerstitial nephritis;

Direct renal parenchymal infection by viral, bacterial or fungal pathogens.

Vascular-dominant nephropathies:

Thrombotic microangiopathy  and

Atherosclerosis

Other nephropathies in the setting of HIV infection:

Diabetic nephropathy and

Age-related nephrosclerosis

Clinical Presentation of a patient with HIV associated nephropathy

Patients with HIV-associated nephropathy (HIVAN) typically present with a nephrotic syndrome consisting of nephrotic-range proteinuria (>3.5 g/d), azotemia, hypoalbuminemia, and hyperlipidemia.

CD4+ T-cell count in patients with HIVAN is usually depressed below 200 cells/µL.

Patients with HIVAN are not typically hypertensive, even in the face of renal insufficiency, and their kidneys are usually normal to large in size and highly echogenic on ultrasonograms.

The urinalysis reveals microhematuria, leukocytes, hyaline casts, and oval fat bodies, but no cellular casts. Serum complement levels are normal.

Electrolyte abnormalities, such as hyponatremia and hyperkalemia, may be observed in patients with HIVAN and may reflect an increase in total body water from the nephrotic syndrome or SIADH.