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Diagnosis: Collapsing glomerulopathy and tubulointestitial nephritis: HIV-associated nephropathy (HIVAN)

HIV-associated nephropathy (HIVAN), formerly known as AIDS-associated nephropathy, is an aggressive form of collapsing focal segmental glomerulosclerosis with accompanying tubular and interstitial lesions. HIVAN was first described among African-Americans and Haitian immigrants with advanced HIV disease, an early suggestion of a strong genetic association. This genetic susceptibility was recently linked to polymorphisms on chromosome 22 in individuals of African descent. The association with advanced HIV infection and evidence from HIV-transgenic mice suggested the possibility that HIV directly infects the kidney and that specific HIV gene expression induces host cellular pathways that are responsible for HIVAN pathogenesis (Wyatt CM, Meliambro K, Klotman PE. Recent progress in HIV-associated nephropathy. Annu Rev Med. 2012;63:147-59. [PubMed link]).

Although collapsing glomerulopathy is most frequently mentioned, other reported glomerular lesions in patients with HIV include IgA nephropathy, cryoglobulinemia, amyloidosis, and a lupus-like immune complex glomerulopathy.

In the preantiretroviral therapy era, HIVAN was characterized by rapid progression to renal failure and end-stage renal disease (ESRD) leading to the need for dialysis. Highly active antiretroviral therapy (HAART) has changed the natural course of this disease, increasing the importance of prompt diagnosis and proper care.

There is evidence for a direct role by HIV in the development of HIVAN. The cellular target in the development of HIVAN is probably the renal glomerular and tubular epithelium. Peculiar histopathologic features of HIVAN are the enhanced proliferation and the loss of differentiation markers of glomerular epithelial cells.

The decision to obtain a biopsy sample is somewhat controversial in the general medical community. Even if a patient presents with the classic clinical features of HIVAN, clinical consideration is predictive of the biopsy diagnosis in only 55-60% of patients. Therefore, to distinguish HIVAN from other forms of renal disease (eg, immune complex glomerulonephritis, immunoglobulin-A nephropathy), patients who are seropositive for HIV require a renal biopsy. The typical practice is to obtain a renal biopsy specimen if the patient's daily protein excretion is greater than 1 g (Salifu MO, Misra N. HIV-Associated Nephropathy. In eMedicine. Sep 2011. Consulted: March 29th, 2012. [Link])

The histologic light microscopy finding is a collapsing form of focal segmental glomerulosclerosis. The glomerular capillary tuft is collapsed and may be segmentally or globally sclerosed. Visceral epithelial cells are hypertrophied and form a characteristic pseudocrescent in the Bowman space. Tubulointerstitial scarring, atrophy, and marked dilatation of the tubules (microcystic dilatations) are usually present. Immunofluorescent microscopy helps to identify positive staining for immunoglobulin G in epithelial cells and for immunoglobulin M, C3, and, occasionally, A in segmental or sclerotic areas. Electron microscopy reveals wrinkling of the basement membranes, epithelial cell proliferation, and foot process effacement. Tubuloreticular structures in the glomerular endothelial cells (consisting of ribonucleoprotein and membrane, the synthesis of which is stimulated by alpha interferon) is highly predictive of HIVAN.

See the Chapter Focal and Segmental Glomerulosclerosis of our Tutorial.

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References

• Salhan D, Sagar A, Kumar D, Rattanavich R, Rai P, Maheshwari S, Adabala M, Husain M, Ding G, Malhotra A, Chander PN, Singhal PC. HIV-associated nephropathy: role of AT2R. Cell Signal. 2012;24(3):734-41. [PubMed link]
• Wyatt CM, Meliambro K, Klotman PE. Recent progress in HIV-associated nephropathy. Annu Rev Med. 2012;63:147-59. [PubMed link]
• Bigé N, Lanternier F, Viard JP, Kamgang P, Daugas E, Elie C, Jidar K, Walker-Combrouze F, Peraldi MN, Isnard-Bagnis C, Servais A, Lortholary O, Noël LH, Bollée G. Presentation of HIV-associated nephropathy and outcome in HAART-treated patients. Nephrol Dial Transplant. 2012;27(3):1114-21. [PubMed link]
• Medapalli RK, He JC, Klotman PE. HIV-associated nephropathy: pathogenesis. Curr Opin Nephrol Hypertens. 2011 May;20(3):306-11. [PubMed link]
• Avila-Casado C, Fortoul TI, Chugh SS. HIV-associated nephropathy: experimental models. Contrib Nephrol. 2011;169:270-85. [PubMed link]
• Salifu MO, Misra N. HIV-Associated Nephropathy. In eMedicine. Sep 2011. Consulted: March 29th, 2012. [Link]

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