Correspondence

Viral Load and HIV-Associated Nephropathy

N Engl J Med 2005; 353:1072-1074September 8, 2005

Article

To the Editor:

Most often, nephropathy associated with human immunodeficiency virus type 1 (HIV-1) occurs after years of HIV-1 infection, although occasional cases of early onset have been described.1 Among patients with early-onset HIV-associated nephropathy, most if not all had associated AIDS.2 We describe a patient with HIV-1 infection and typical features of HIV-associated nephropathy yet no history of AIDS and an undetectable viral load in both blood and kidney tissue.

A 35-year-old African woman with known HIV-1 infection without coinfection with hepatitis B or C virus was hospitalized because of a five-day history of fatigue and weight loss. She had been receiving highly active antiretroviral therapy (HAART) (lamivudine, didanosine, and efavirenz) for two years, and she had an undetectable plasma HIV-1 RNA level (<20 copies per milliliter) and a CD4 cell count of 350 per cubic millimeter. Laboratory studies revealed a white-cell count of 10,000 per cubic millimeter (with 50 percent lymphocytes), a hemoglobin level of 10.2 g per deciliter, a platelet count of 365,000 per cubic millimeter, a serum creatinine level of 4.0 mg per deciliter, and a serum albumin level of 2.2 g per deciliter. Urinalysis revealed a daily protein excretion of 7 g and 30 red cells per high-power field. A kidney biopsy was performed one week after the woman was admitted to the hospital.

Biopsy specimens were prepared according to standard techniques and subjected to immunostaining for synaptopodin and Ki-67, as previously described.3 HIV-1 proviral DNA (defined as undetectable at <100 copies per milliliter) was quantified in duplicate with the use of a real-time polymerase-chain-reaction (PCR) assay in peripheral-blood mononuclear cells and in a kidney-biopsy specimen.4 Three of the 10 glomeruli examined had the following findings consistent with HIV-associated nephropathy: areas of capillary collapse and focal glomerulosclerosis, numerous dilated microcyst tubules that contained large proteinaceous casts, and moderate interstitial infiltration (Figure 1AFigure 1Kidney Biopsy Two Years after the Initiation of HAART in a Patient with Typical Features of HIV-Associated Nephropathy.). Staining for synaptopodin was weak in the podocytes of collapsed glomeruli (Figure 1B) and noncollapsed glomeruli, as previously described in relatively inactive5 or treated HIV-associated nephropathy.1 Ki-67 was detected in the epithelial cells of microcystic tubules (Figure 1C). The proviral DNA load according to the ultrasensitive quantitative PCR assay was undetectable in both plasma (80 copies per 150,000 leukocytes) and kidney tissue (50 copies per 150,000 cells).

Five to 15 percent of patients with well-controlled HIV-1 infection and with an undetectable viral load in blood may have histologic stigmata of HIV-associated nephropathy.5 However, in those patients, actual AIDS occurred in the course of their disease, which was not the case in our patient. Synaptopodin, normally found only in mature podocytes, is lost in HIV-associated nephropathy,1,3 and the podocytes undergo proliferation, as indicated by the expression of Ki-67. In our case, though, and contrary to the data published by Winston et al.,1 these findings (Figure 1B and Figure 1C) were in the context of excellent viral control in blood and in the kidney, suggesting the presence of an as yet undetermined factor in the development of HIV-associated nephropathy. We suggest that HIV-associated nephropathy may occur at any stage of HIV-1 infection.

Hassane Izzedine, M.D.
Marc Wirden, M.D.
Vincent Launay-Vacher, M.D.
Pitié–Salpétrière Hospital, 75013 Paris, France
hassan.izzedine@psl.ap-hop-paris.fr

5 References

1. 1

   Winston JA, Bruggeman LA, Ross MD, et al. Nephropathy and establishment of a renal reservoir of HIV type 1 during primary infection. N Engl J Med 2001;344:1979-1984
   Full Text | Web of Science | Medline

2. 2

   Lucas GM, Eustace JA, Sozio S, Mentari EK, Appiah KA, Moore RD. Highly active antiretroviral therapy and the incidence of HIV-1-associated nephropathy: a 12-year cohort study. AIDS 2004;18:541-546
   CrossRef | Web of Science | Medline

3. 3

   Barisoni L, Kriz W, Mundel P, D'Agati V. The dysregulated podocyte phenotype: a novel concept in the pathogenesis of collapsing idiopathic focal segmental glomerulosclerosis and HIV-associated nephropathy. J Am Soc Nephrol 1999;10:51-61
   Web of Science | Medline

4. 4

   Bieche I, Olivi M, Champeme MH, Vidaud D, Lidereau R, Vidaud M. Novel approach to quantitative polymerase chain reaction using real-time detection: application to the detection of gene amplification in breast cancer. Int J Cancer 1998;78:661-666
   CrossRef | Web of Science | Medline

5. 5

   Szczech LA, Gupta SK, Habash R, et al. The clinical epidemiology and course of the spectrum of renal diseases associated with HIV infection. Kidney Int 2004;66:1145-1152
   CrossRef | Web of Science | Medline

Citing Articles (12)

Citing Articles

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   Shivaram Hegde, Cheentan Singh, Bernadette Óhare. (2011) HIV-associated nephropathy in the setting of maximal virologic suppression. Pediatric Nephrology 26:6, 973-977
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2. 2

   H. Izzedine, V. Acharya, M. Wirden, P. Cluzel, D. Sene, G. M. Lucas, A. Baumelou, M. G. Atta. (2011) Role of HIV-1 DNA levels as clinical marker of HIV-1-associated nephropathies. Nephrology Dialysis Transplantation 26:2, 580-583
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   Hee Jin Kim, Stacy Lee, Jae U. Jung. (2010) When autophagy meets viruses: a double-edged sword with functions in defense and offense. Seminars in Immunopathology 32:4, 323-341
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   Mohamed G. Atta. (2010) Diagnosis and Natural History of HIV-Associated Nephropathy. Advances in Chronic Kidney Disease 17:1, 52-58
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   Marina Núñez, Anita M. Saran, Barry I. Freedman. (2010) Gene-Gene and Gene-Environment Interactions in HIV-Associated Nephropathy: A Focus on the MYH9 Nephropathy Susceptibility Gene. Advances in Chronic Kidney Disease 17:1, 44-51
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   Warren A. Andiman, Miriam C. Chernoff, Charles Mitchell, Murli Purswani, James Oleske, Paige L. Williams, Hans Spiegel, Phil Gona, George R. Seage. (2009) Incidence of Persistent Renal Dysfunction in Human Immunodeficiency Virus-Infected Children. The Pediatric Infectious Disease Journal 28:7, 619-625
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   Mohamed G Atta, Gregory M Lucas, Derek M Fine. (2008) HIV-associated nephropathy: epidemiology, pathogenesis, diagnosis and management. Expert Review of Anti-infective Therapy 6:3, 365-371
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8. 8

   T. I. de Silva, F. A. Post, M. D. Griffin, D. H. Dockrell. (2007) HIV-1 Infection and the Kidney: An Evolving Challenge in HIV Medicine. Mayo Clinic Proceedings 82:9, 1103-1116
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9. 9

   L Zafrani, P Coppo, S Dettwiler, V Molinier-Frenkel, F Agbalika, J-B Guiard-Schmid, G Pialoux, Y-C Xu-Dubois, E Rondeau, A Hertig. (2007) Nephropathy associated with the diffuse infiltrative lymphocytosis syndrome. Kidney International 72:2, 219-224
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10. 10

    Hassane Izzedine, Gilbert Deray. (2007) The nephrologist in the HAART era. AIDS 21:4, 409-421
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    Michelle Estrella, Derek M. Fine, Joel E. Gallant, M. Hafizur Rahman, Nagapradeep Nagajothi, Lorraine C. Racusen, Paul J. Scheel, Mohamed G. Atta. (2006) HIV Type 1 RNA Level as a Clinical Indicator of Renal Pathology in HIV‐Infected Patients. Clinical Infectious Diseases 43:3, 377-380
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12. 12

    Hassane Izzedine, Florence Damond, Isabelle Brocheriou, Jade Ghosn, Hassina Lassal, Gilbert Deray. (2006) HIV-2 infection and HIV-associated nephropathy. AIDS 20:6, 949-950
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