Viral Load and HIV-Associated Nephropathy
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《新英格兰医药杂志》
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 1A). 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).
Figure 1. Kidney Biopsy Two Years after the Initiation of HAART in a Patient with Typical Features of HIV-Associated Nephropathy.
Kidney-biopsy specimens show segmental collapse of the glomerular tuft and marked hyperplasia of the overlying podocytes with focal sclerosis and patchy mild interstitial fibrosis. Many proximal tubules show degenerative changes, and some focal tubular microcysts contain large casts (Panel A, trichrome stain). Immunostaining for synaptopodin shows an irregular and weak staining in the podocytes of an ischemic glomerulus (Panel B). Many nuclei in the epithelial cells of the renal tubules stain for Ki-67 (Panel C).
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
References
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.
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.
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.
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.
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.
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 1A). 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).
Figure 1. Kidney Biopsy Two Years after the Initiation of HAART in a Patient with Typical Features of HIV-Associated Nephropathy.
Kidney-biopsy specimens show segmental collapse of the glomerular tuft and marked hyperplasia of the overlying podocytes with focal sclerosis and patchy mild interstitial fibrosis. Many proximal tubules show degenerative changes, and some focal tubular microcysts contain large casts (Panel A, trichrome stain). Immunostaining for synaptopodin shows an irregular and weak staining in the podocytes of an ischemic glomerulus (Panel B). Many nuclei in the epithelial cells of the renal tubules stain for Ki-67 (Panel C).
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
References
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.
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.
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.
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.
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.