Membranous glomerulonephritis with nephrotic syndrome in a HIV positive patient—remarkable remission with triple therapy

A. Alarcón-Zurita1, A. Salas2, E. Antón3, A. Morey1, M. A. Munar1, P. Losada1 and J. Martinez1

1 Servicio de Nefrologia, 2 Servicio de Medicina Interna, 3 Servicio Anatomia Patólogica, Hospital Son Dureta, Palma de Mallorca, Spain

Sir,

We observed membranous glomerulonephritis in a homosexual patient with intravenous drug abuse who was positive for human immunodeficiency virus (HIV) and hepatitis C virus (HCV). Partial remission of the nephrotic syndrome was observed after administration of triple therapy comprising idinavir, estavudin and lamivudin.

Case.

HIV seropositivity was first diagnosed in this 40-year-old homosexual drug addict in 1989. He underwent several drug detoxification treatments. He acquired HCV-positive hepatitis with marked hepatosplenomegaly with discrete elevation of hepatic enzymes (no hepatic biopsy) as well as herpes zoster with unremarkable evolution and several minor infections, notably non-specific granulomatous lymphadenitis which was treated with tuberculostatic agents, although tuberculous bacilli could not be cultivated.

Since 1989 he was treated with zidovudine, didanosine and zalkitavine singly or in combination, but never more than two. Until 1995 CD-4 and CD-8 cells were approximately 32% and 48%, respectively. HIV antigen tests were positive in all determinations. In 1995, during a routine control, marked hypoproteinaemia (4.1 g/l) was noted and work-up showed proteinuria of 12.5 g/24 h. Despite marked biochemical evidence of nephrotic syndrome, there were no clinical signs, particularly no oedema. Apart from moderate hepatosplenomegaly there were no signs on physical examination.

Laboratory evaluation showed Hb 13.7 g/dl, leucocytes 2410 mm-3, lymphocytes 530 mm-3, CD-4 13%, CD-8 52%, HIV 2058 copies/ml, plasma creatinine 1.2 mg/dl, creatinine clearance 92 ml/min, blood glucose 90 mg/dl, normal plasma Na and K concentrations, total protein 4.5 g/l, albumin 1.6 g/l, GOT 21 U, GPT 17 U, and gamma-GT 74 U. Immunoglobulin, complement, cryoglobulin, rheumatoid factor, ANA and ANCA were normal.

Proteinuria was 12.5 g/24 h and urinary sediment was normal. Renal biopsy (Figures 1Go and 2Go) showed consistent thickening of the basal membrane of glomeruli without any proliferation. With silver-methynamin technique spike formation was demonstrated. No significant changes of tubuli, vessels or interstitium were noted. Immunofluorescence documented pseudolinear granular deposits of C3 and IgG, diffusely along the basal membrane and focal deposits of IgM and C1q (membranous glomerulonephritis, stage III after Churg and Strauss). No specific treatment was given for membranous glomerulonephritis, but treatment for the HIV infection was administered, i.e. a combination of Ritonavir and Estavudin. The virus load was approximately 3000 copies/ml. Renal function and protein excretion (12 g/24 h) did not change.



View larger version (135K):
[in this window]
[in a new window]
 
Fig. 1. Membranous glomerulonephritis type II. [Engrosamientoimportante de las paredes capilares sin proliferación celular. (Tincióncon PASx200)].

 


View larger version (143K):
[in this window]
[in a new window]
 
Fig. 2. Membranous glomerulonephritis. [Espículasargirófilas enla vertiente epitelial de la membrana basal. (Tinción platametenaminax200)].

 
In 1997 triple therapy comprising indinavir, estavudin and lamivudine was given. A control examination 4 months later showed the following: Hb 15 g/dl, CD-4 cells 34%, CD-8 cells 50%, plasma creatinine 1.4 mg/dl, creatine clearance 83 ml/min, and proteinuria 0.8 g/24 h. The viral load was not determined. Subsequently the patient travelled to India. Because of diarrhoea, treatment was withheld for 8 days. The viral load rose to 17 553 copies/ml and proteinuria to 3.8 g/24 h. These findings persisted despite resumption of triple therapy with reduction of viraemia to 200 copies/ml.

Comment.

Our patient had multiple viral infections, e.g. HCV and seroconversion for HBV. Consequently, we are not absolutely certain that the above glomerulonephritis was caused by HIV and not by some other virus. Unfortunately, demonstration of viral antigens in the immune deposits could not be performed. Nevertheless, some considerations are appropriate. At no point was our patient HBs-antigen positive, so that a causal role of HBV is unlikely. It is true that he was positive for HCV-RNA by PCR. Nevertheless, this virus is mostly associated with membranoproliferative glomerulonephritis in association with cryoglobulinaemia whereas our patient, as is typical for HIV-associated nephropathy, presented with marked biochemical, but not clinical, evidence of nephrotic syndrome, particularly no oedema. We entertained the hypothesis (despite the absence of direct evidence) that the patient's glomerulonephritis was due to HIV-antigen-containing immune complexes. In view of the threatening nature of the nephrotic syndrome, this consideration led to aggressive treatment of the HIV infection, ultimately triple therapy comprising Indinavir, Stavudin and Lamivudine. As described, this caused partial remission of the nephrotic syndrome and reduction of the virus load. Partial remission of the nephrotic syndrome with such aggressive therapy is encouraging, but to exclude coincidence, confirmation by other observations is required. It is for this purpose that we felt that communication of this unusual clinical course to clinical nephrologists was useful.

Acknowledgments

We thank Professor Ritz for translating the text from Spanish to English.

References

  1. Gardenswartz MH, Lemer CW, Seligson GR et al. Renal disease in patients with AIDS: A clinicopathologic study. Clin Nephrol1984; 21: 197–204[ISI][Medline]
  2. D'Agati V, Suh JI, Carbone L et al. The pathology of HIV nephropathy: A detailed morphologic and comparative study. Kidney Int1989; 35: 1358–1370[ISI][Medline]
  3. Rao TK, Friedman IEA, Nicastri AD. The types of renal disease in the acquired immunodeficiency syndrome. N Engl J Med1987; 316: 1062–1068[Abstract]
  4. Kimmel P, Phillips TM, Ferreira-Centeno A et al. HIV-associated immune mediated renal disease. Kidney Int1993; 44: 1327–1340[ISI][Medline]
  5. Rarick MU, Espina B, Mocharnuck R et al. Thrombotic thrombocytopenic purpura in patients with human immunodeficiency virus infection. A report of three cases and review of the literature. Am J Hematol1992; 40: 103–109[ISI][Medline]
  6. Yoshikawa N, Ito H, Yamada Y et al. Membranous glomerulonephritis associated with hepatitis B antigen in children: a comparison with idiopathic membranous glomerulonephritis. Clin Nephrol1985; 23: 28–34[ISI][Medline]
  7. Gonzalo A, Barcena R, Mampaso F et al. Membranoproliferative glomerulonephritis and hepatitis C infection. Nephron1993; 63: 475–476[ISI][Medline]
  8. D'Agati V, Appel GB. HIV infection and the kidney. J Am Soc Nephrol1997; 6: 139–152[ISI][Medline]
  9. Ifudu O, Rao TKS, Tan CC et al. Zidovudine is beneficial in human immunodeficiency virus-associated nephropathy. Am J Nephrol1995; 5: 217–221
  10. Michel C, Dosquet P, Ronco P et al. Nephropathy associated with infection by human immunodeficiency virus: A report of 11 cases including 6 treated with zidovudine. Nephron1992; 62: 434–440[ISI][Medline]