HIV Infection and Chronic Kidney Disease
lesions. By immunofluorescence, as in other types of FSGS, focal and segmental deposits of IgM and, more rarely, C3c are present. Electron microscopy shows foot process fusion plus glomerular capillary loop sclerosis. Some tubulo-reticular inclusions are observed. Clinical presentation is with either nephrotic syndrome or urinary abnormalities and evolution to end-stage renal disease is a frequent feature.
Personal Experience
The authors recently published a review of renal biopsies from 73 ART-untreated patients with HIV infection and glomerular involvement, performed over a period of more than 20 years in a single nephrology unit in Milan.33
were evaluated and defined by histological patterns.
The single types of glomerular involvement Clinical
presentation was also recorded. Three main histological groups were identified: HIVAN (or collapsing FSGS) and, among non-HIVAN cases, immune-complex glomerulonephritis and nephropathies not related to immune-complex deposition (see Table 1). Peculiar aspects that can differentiate these forms from the corresponding non-HIV nephropathies were described. Such peculiar aspects, in the authors’ experience, were multiple site deposits (see Figure 1), higher tendency to sclerosis, numerous protein droplet inclusions in visceral epithelial cell cytoplasm and tubulo-reticular inclusions in endothelial cell cytoplasm of glomerular and tubular capillaries.
According to literature and the authors’ experience, if nephrotic syndrome associated with a recent decline in renal function is present in a subject of African descent with low CD4 count, high viral load and no oedema or hypertension, a pattern of HIVAN is the most likely histological diagnosis at renal biopsy.
In HIV-positive Caucasian patients with nephrotic-range proteinuria, common diagnoses include classic NC-FSGS, MPGN and LL-GN. In patients with non-nephrotic proteinuria, regardless of their ethnic group, mesangial proliferative glomerulonephritis, IgAN and, more rarely, membranous glomerulonephritis can be found at renal biopsy.
In summary, when dealing with a patient affected by HIV infection and CKD, as evidenced by proteinuria and/or nephrotic syndrome and a variable degree of renal function impairment, the authors strongly
1. Post FA, et al., Curr Opin Infect Dis, 2009;22:43–48. 2. Wyatt CM, et al., Clin J Am Soc Nephrol, 2007;2:S20–S24. 3. Wyatt CM, et al., Kidney Int, 2009;75:428–34. 4. Campbell LJ, et al., HIV Med, 2009;10:329–36. 5. Barisoni L, et al., J Am Soc Nephrol, 1999;10:51–61. 6. Dickie P, et al., Virology, 1991;185:109–19. 7. Zuo Y, et al., J Am Soc Nephrol, 2006;17:2832–43. 8. Gonzalez E, et al., Science, 2005;307:1434–40. 9. Liu XH, et al., Kidney Int, 1999;55:1491–1500. 10. Hatsukari I, et al., J Am Soc Nephrol, 2007;18:780–87. 11. Mack M, et al., Nat Med, 2000;6:769–75. 12. Marras D, et al., Nat Med, 2002;8:522 –26. 13. Alpers CE, et al., Am J Kidney Dis, 1992;19:126–30. 14. Tokizawa S, et al.,Kidney Int, 2000;58:607–17. 15. Monsuez JJ, et al., Int J Cardiol, 2009;133:293–306. 16. Kapasi A, et al., Inflammation, 1998;22:137–44. 17. Singhal PC, et al., J Investig Med, 1998;46:243–48. 18. Conaldi PG, et al., Am J Pathol, 2002;161:53–61.
recommend that a renal biopsy be performed. This is because of the wide spectrum of glomerular and tubular diseases that can be observed in this group of patients.
Concluding Remarks
HIV-infected subjects can be affected by a wide spectrum of kidney diseases that frequently progress to CKD despite therapy. For this reason, renal biopsy remains an essential procedure for correct diagnostic and prognostic evaluation in the ART era. Further research is certainly needed to clarify the diverse pathogenetic mechanisms leading to renal damage. As recently pointed out by an analysis published in Nature Medicine,51
a back-to-basics approach is mandatory
to learn more about the biology of HIV infection. Overeagerness to translate results should not eclipse the basic research needed to address fundamental scientific questions, with the final goal of designing more specific and effective therapeutic approaches. n
Manuela Nebuloni works in the Pathology Unit at the ‘L Sacco’ Department of Clinical Sciences at the University of Milan. She focuses her research mainly on renal pathology, AIDS-associated infectious diseases and, more recently, the study of murine and human models regarding the expression of mediators involved in inflammatory and neoplastic lesions. She graduated in medicine and has a post-graduate degree in pathology.
Antonella Tosoni is a Biologist in the Pathology Unit at the ‘L Sacco’ Department of Clinical Sciences at the University of Milan, specialising in microbiology and virology. She is responsible for the diagnostic and research activities in the electron microscopy laboratory. Her research interests include renal pathology, congenital dermopathology, infectious diseases and, in particular, the expression of specific ultrastructural phenotypes in various conditions and their aetiological implications.
Giovanni Barbiano di Belgiojoso is Head of the Renal Unit at ‘L Sacco’ University Hospital and a Professor of Nephrology at the University of Milan. He is a member of the International Society of Nephrology (ISN), the European Renal Association– European Dialysis and Transplantation Association (ERA-EDTA) and the American Society of Nephrology (ASN). He has published 350 papers on clinical and histological aspects of glomerulonephritis, with a special interest in renal involvement in HIV infections.
Maria Pia Rastaldi is Director of the Renal Research Laboratory at Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico of Milan. She is a member of the Histochemical Society, the Italian Society of Nephrology, the European Renal Association–European Dialysis and Transplantation Association (ERA-EDTA), the American Society of Investigative Pathology (ASIP) and the Renal Pathology Society. Her research interests focus on human and experimental renal pathology, podocyte biology and intercellular signalling in the glomerulus.
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