A lupus-like glomerulonephritis following acute HIV-1 seroconversion in an African woman

Marie Matignon1, Olivier Lidove1, Emmanuel Dupuis2, Francine Walker3, Sophie Abgrall4 and Thomas Papo1

1 Internal Medicine Unit, 2 Nephrology Unit, 3 Pathology Unit and 4 Infectious Diseases Unit, Bichat Hospital, 46 rue Henri Huchard, 75877 Paris cedex 18, France

Correspondence and offprint requests to: Thomas Papo, MD, Internal Medicine Unit, Bichat Hospital, 46 rue Henri Huchard, 75877 Paris cedex 18, France. Email: thomas.papo{at}bch.ap-hop-paris.fr

Keywords: diffuse proliferative lupus nephropathy; HIV; HIV protease inhibitor



   Introduction
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 Introduction
 Case
 Discussion
 References
 
Human immunodeficiency virus (HIV)-associated nephropathy (HIVAN) is a distinct clinico-pathological entity that is characterized by a proteinuria in the nephrotic range and, in the absence of antiretroviral therapy, rapid progression to end-stage renal disease. HIVAN comprises only HIV-associated glomerulopathies and does not include the tubular disorders or Fanconi syndrome observed in HIV patients [1]. Its most common renal manifestation is the collapsing variant of focal segmental glomerular sclerosis. HIVAN has a racial predilection, affecting blacks more than whites. Micropathological studies have expanded the spectrum of glomerular lesions in HIV-infected patients to include immune complex-mediated glomerulonephritides: immunoglobulin A nephropathy, membranoproliferative glomerulonephritis (MPGN) and lupus-like immune complex glomerulonephritis. All three of these pathological variants, however, are much less common in blacks. To our knowledge, a lupus-like immune complex glomerulonephritis has not been described during acute HIV seroconversion; furthermore, its optimal treatment in such a setting has not been entirely codified.

We report a case of lupus-like immune complex glomerulonephritis in a black woman with acute HIV seroconversion who was treated with antiretroviral therapy alone.



   Case
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 Introduction
 Case
 Discussion
 References
 
A 28-year-old African woman from the Ivory Coast was admitted in November 2001 because of high-grade fever and nephritis. She had never used tobacco, alcohol or drugs, but she had had unprotected sex with a single partner (HIV status unknown). Her past history was unremarkable. Three months earlier, she had been found negative on routine testing for HIV-1 and -2 infections. Two weeks before admission, she had an influenza-like syndrome, and was treated with amoxicillin and acetaminophen for 15 days, with no improvement. Her temperature was 39°C, and she had lost 5 kg. Physical examination disclosed a normal blood pressure and diffusely enlarged lymph nodes and spleen, with no peripheral oedema.

Blood tests showed: haemoglobin at 80 g/l, platelets at 231 x 109/l with no schizocytes, blood creatinine 123 µmol/l, creatinine clearance (estimated by the Cockroft and Gault formula [2]) 46 ml/min and blood albumin 16 g/l. A 24 h urine collection contained 8.25 g of protein. Urine protein electrophoresis showed an 80% albumin content. HIV-1 antibodies were detected using both enzyme-linked immunosorbent assay (ELISA) and western blot. The RNA viral load was 173 copies/l. The viral core p24 antigen was found in her serum. Her CD4-positive lymphocyte count was 193/ml. A large panel testing for superinfections—including Cryptococcus neoformans, Toxoplasma gondii, Treponema pallidum, Plasmodium falciparum, Epstein–Barr virus, cytomegalovirus, hepatitis A virus and hepatitis C virus—was negative. The patient had serum anti-HBs and anti-HBc antibodies.

An antinuclear antibody (ANA) titre of 1:80 was considered insignificant. Her serum tested negative for antibodies to anti-double-stranded DNA and anti-extractable nuclear antigens. Anticardiolipin serum antibodies were elevated to 80 UGPL (n<20), with anti-ß-2-glycoprotein 1 antibodies at 15 IU (n<10). Repeated testing for lupus anticoagulant activity was negative, as was the VDRL test. Blood levels of complement components (C3 and C4) were normal.

A renal biopsy was performed. Paraffin sections for light microscopy contained eight glomeruli, with endocapillary proliferation, mesangial hypercellularity and matrix accumulation present in all eight. The collapsing form of glomerular sclerosis was not observed. Capillary walls were thickened. Tubulointerstitial changes included interstitial inflammatory cell infiltration and oedema, tubular epithelial oedema and microcyst formation. The arteries and arterioles did not show prominent changes. Frozen sections for immunofuorescence contained eight glomeruli. Direct immunofluorescence showed a diffuse, coarsely granular glomerular capillary and mesangial fluorescence for IgA, IgG, IgM, C3 and C1q. The test for fibrinogen was negative.

Histopathology was suggestive of a ‘lupus-like’ glomerulopathy (Figure 1A–D).



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Fig. 1. (A) Glomerular lesions correspond to the increase of mesangial matrix and cellularity and intracapillary proliferation. The thickened capillary walls result from immune deposits (arrow). Masson's trichrome x400. (B) Methenamine silver staining showing epimembranous spikes (arrow) and double-contoured glomerular basal membrane (*). Magnification x400. (C) Presence of diffuse granular staining of the capillary wall and mesangium. Anti-human IgG. Magnification x300. (D) Diffuse and abundant peripheral capillary wall and mesangium granular staining. Fluorescein isothiocyanate anti-human C1q. Magnification x300.

 
Highly active antiretroviral therapy (HAART) was started in December 2001, including lamivudine, zidovudine, nelfinavir and efavirenz. Because of a haemolysis related to a glucose-6-phosphate dehydrogenase deficiency, zidovudine was stopped and switched to stavudine. Angiotensin-converting enzyme (ACE) inhibition could not be pursued because of low blood pressure. Six months after her admission, the patient's physical examination was normal as she continued on lamivudine, ritonavir, nelfinavir and efavirenz. Her CD4-positive lymphocyte count was 400/ml, serum creatinine 61 µmol/l, creatinine clearance 95 ml/min and serum albumin 31 g/l; and a 24 h urine collection contained 3.61 g of protein. After 2 years and 6 months (April 2004), her serum creatinine was 60 µmol/l and albumin 34 g/l, and her 24 h urine collection showed no proteinuria.

Renal disease in this young African woman was related to a lupus-like immune complex glomerulonephritis in the context of acute HIV seroconversion.



   Discussion
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 Introduction
 Case
 Discussion
 References
 
The prevalence of renal disease in HIV-infected patients is ~10%, but only 2% of renal lesions appear to be specifically related to HIV infection [1].

Two forms of glomerular lesions are found predominantly on renal biopsies in HIVAN. The most common finding is the collapsing variant of focal segmental glomerular sclerosis, which has been reported in all stages of HIV infection, including acute seroconversion [3,4]. Most such cases in the USA are among young, African–American men. HIVAN with focal glomerulosclerosis is the third leading cause of end-stage renal disease in the USA among African–American males between the ages of 20 and 64; this nephropathy is also more severe in blacks [1]. In Europe, HIVAN with focal glomerulosclerosis was also found predominantly in black patients [4,5].

The second common glomerulopathy is the HIV-associated immune complex-mediated glomerulonephritis. It occurs much less frequently in the USA: 25–33%. As seen in reports from the UK, France and Italy, it appears to be more common in Europe than the nephropathy with focal glomerulosclerosis, and it mostly affects Caucasian patients [1,4,5]. Its exact population distribution is not known. Immunoglobulin A nephropathy has also been reported to occur in individuals of both European and African descent, despite the rarity of the typical immunoglobulin A nephropathy in the black population. Its incidence and prevalence are unknown. MPGN may be the most common of the immune complex-mediated glomerulonephritides seen in HIV-infected patients (mostly among intravenous drug abusers co-infected with HIV and hepatitis C virus). A lupus-like immune complex glomerulonephritis has also been reported; 10 cases in Nochy's study (four blacks and six whites). Most patients had no ANA or anti-double-stranded DNA antibodies, and had normal complement levels [4,5].

Systemic lupus and HIV infection share many clinical features including constitutional symptoms, blood and skin abnormalities, musculoskeletal disease, lymphadenopathy, neuropathy and renal disease. However, a true co-existence of HIV infection and systemic lupus is rare [6]. Although many patients with HIV infection have high levels of circulating immune complexes, polyclonal gammopathy and autoantibodies (mostly low titre ANA and antiphospholipid antibodies), the specific features of systemic lupus, such as the anti-double-stranded DNA and the anti-extractable nuclear antigens antibodies, are usually lacking. Patients with active lupus nephritis show low levels of complement which are usually normal in HIV patients [6,7]. No single histopathological finding is pathognomonic per se for lupus nephritis, as most of its features may also be seen in MPGN; however, prominent C1q deposits is an uncommon feature in MPGN. To our knowledge, no case of HIV-associated lupus-like immune complex glomerulonephritis has been described previously during or following acute HIV seroconversion [7].

The treatment of classical HIV-associated nephropathy with focal glomerulosclerosis may include the use of corticosteroids, ACE inhibitors and anti-retroviral drugs [8]. HAART has been associated with a substantial reduction in the incidence of HIVAN [9]. Although prior reports suggest that increased CD4-positive lymphocyte counts and undetectable levels of HIV RNA are associated with better renal outcome [10], the optimal treatment of HIV-associated nephropathy with focal glomerulosclerosis has not yet been codified. The use of corticosteroids remains a topic of intense debate [1]. Sporadic case reports describe improvement in renal function with the use of anti-retroviral drugs, ACE inhibitors or corticosteroids in patients with HIV-associated immune complex nephropathy [1,8]. A recent case report suggests that HAART may preserve renal function in HIV-associated lupus-like nephritis [7]. Our patient's renal disease improved with antiviral therapy alone and stabilized over a 30-month follow-up.

In summary, we consider our African patient to have suffered from renal disease related to an HIV-specific lupus-like immune complex glomerulonephritis, because: (i) light microscopy and the immunofluorescence study of her kidney biopsy showed typical features of proliferative glomerulonephritis with immune deposits; (ii) she showed no clinical or laboratory signs of systemic lupus erythematosus; (iii) concomitant HIV-1 infection and acute seroconversion were defined; and (iv) renal function improved under HAART alone, without corticosteroids.

Lupus-like immune complex glomerulonephritis may occur early in the course of HIV infection in blacks. An anti-retroviral regimen should be tried alone as a first-line treatment.

Conflict of interest statement. None declared.



   References
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 Introduction
 Case
 Discussion
 References
 

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  8. Wei A, Burns GC, Williams BA et al. Long-term renal survival in HIV-associated nephropathy with angiotensin-converting enzyme inhibition. Kidney Int 2003; 64: 1462–1471[CrossRef][ISI][Medline]
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Received for publication: 30. 7.04
Accepted in revised form: 11.10.04





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