Pediatric Nephrology

, Volume 27, Issue 6, pp 981–989 | Cite as

Chronic kidney disease associated with perinatal HIV infection in children and adolescents

  • Murli U. Purswani
  • Miriam C. Chernoff
  • Charles D. Mitchell
  • George R. SeageIII
  • Gaston Zilleruelo
  • Carolyn Abitbol
  • Warren A. Andiman
  • Kathleen A. Kaiser
  • Hans Spiegel
  • James M. Oleske
  • The IMPAACT 219/219C Study Team
Original Article

Abstract

Background

This study describes the incidence, clinical and demographic characteristics, and spectrum of chronic kidney disease (CKD) in youths with perinatal HIV-1 infection.

Methods

Retrospective analysis between May 1993 and December 2006 of subjects with renal disease followed in the Pediatric AIDS Clinical Trials Group 219/219C multicenter study examining the long-term consequences of perinatal HIV infection. Diagnosis confirmation was made utilizing a questionnaire mailed to research sites. Participants with CKD of other etiology than HIV were excluded. Outcome measures were biopsy-diagnosed CKD and, in the absence of biopsy, HIV-associated nephropathy (HIVAN) using established clinical criteria.

Results

Questionnaires on 191 out of 2,102 participants identified 27 cases of CKD: 14 biopsy-diagnosed and 6 clinical cases of HIVAN, and 7 biopsy-diagnosed cases of immune complex-mediated kidney disease (lupus-like nephritis, 3; IgA nephropathy, 2; membranous nephropathy, 2). Incidence rates for CKD associated with HIV in pre-highly active antiretroviral therapy (HAART) (1993–1997) and HAART (1998–2002, 2003–2006) eras were 0.43, 2.84, and 2.79 events per 1,000 person years respectively. In multivariate analysis, black race and viral load ≥100,000 copies/mL (rate ratios 3.28 and 5.05, p ≤ 0.02) were associated with CKD.

Conclusions

A variety of immune complex-mediated glomerulonephritides and HIVAN occurs in this population. Black race and uncontrolled viral replication are risk factors for CKD associated with HIV.

Keywords

HIVAN HIV immune complex kidney disease FSGS Renal Youth Proteinuria Biopsy 

Notes

Research funding and support

Overall support for the International Maternal Pediatric Adolescent AIDS Clinical Trials Group (IMPAACT) was provided by the National Institute of Allergy and Infectious Diseases (NIAID; U01 AI068632), the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), and the National Institute of Mental Health (NIMH; AI068632). This work was supported by the Statistical and Data Analysis Center at Harvard School of Public Health, under the National Institute of Allergy and Infectious Diseases cooperative agreement #5 U01 AI41110 with the Pediatric AIDS Clinical Trials Group (PACTG) and #1 U01 AI068616 with the IMPAACT Group. Support of the sites was provided by the National Institute of Allergy and Infectious Diseases (NIAID) and the NICHD International and Domestic Pediatric and Maternal HIV Clinical Trials Network funded by the NICHD (contract number N01-DK-9-001/HHSN267200800001C). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. The funders were not involved in the design and conducting of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript.

Murli U. Purswani, Miriam C. Chernoff, and Charles D. Mitchell had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

We would like to thank the children and families for their participation in PACTG 219/219C and the individuals and institutions involved in the conduct of 219/219C (ESM 4).

Supplementary material

467_2011_2097_MOESM1_ESM.doc (249 kb)
ESM 1 Renal event report: Questionnaire mailed to the clinical research sites (DOC 249 kb)
467_2011_2097_MOESM2_ESM.doc (64 kb)
ESM 2 Fig. 1 Identification of 27 cases of chronic kidney disease associated with HIV, PACTG 219/219C cohort, 1993–2006 (DOC 64.5 kb)
467_2011_2097_MOESM3_ESM.docx (14 kb)
ESM 3 Table: Univariate Poisson regression analysis of characteristics and incidence rates for chronic kidney disease associated with HIV, PACTG 219/219C Cohort, 1993 through 2004 (DOCX 14.1 kb)
467_2011_2097_MOESM4_ESM.doc (34 kb)
ESM 4 Acknowledgements (DOC 34.0 kb)

References

  1. 1.
    Gortmaker SL, Hughes M, Cervia J, Brady M, Johnson GM, Seage GR III, Song LY, Dankner WM, Oleske JM, Pediatric AIDS Clinical Trials Group Protocol 219 Team (2001) The impact of protease inhibitor combination therapy on mortality among children and youth infected with HIV-1. N Engl J Med 345:1522–1528PubMedCrossRefGoogle Scholar
  2. 2.
    Palella FJ Jr, Baker RK, Moorman AC, Chmiel JS, Wood KC, Brooks JT, Holmberg SD, HIV Outpatient Study Investigators (2006) Mortality in the highly active antiretroviral therapy era: changing causes of death and disease in the HIV outpatient study. J Acquir Immune Defic Syndr 43:27–34PubMedCrossRefGoogle Scholar
  3. 3.
    Pater K, Hernan MA, Williams PL, Seeger JD, Mclntosh K, Van Dyke RB, Seage GR III, Pediatrics AIDS Clinical Trials Group 219/219C Study Team (2008) Long-term effectiveness of highly active antiretroviral therapy on the survival of children and adolescents with HIV-1 infection: a 10-year follow-up study. Clin Infect Dis 46:507–515CrossRefGoogle Scholar
  4. 4.
    Antiretroviral Therapy Cohort Collaboration (2008) Life expectancy of individuals on combination antiretroviral therapy in high-income countries: a collaborative analysis of 14 cohort studies. Lancet 372:293–299CrossRefGoogle Scholar
  5. 5.
    Brandy MT, Oleske JM, Williams PL, Elgie C, Mofenson LM, Dankner WM, Van Dyke RB, Pediatric AIDS Clinical Trials Group 219/219C Team (2010) Declines in mortality rates and changes in causes of death in HIV-1-infected children during the HAART era. J Acquir Immune Defic Syndr 53:86–94CrossRefGoogle Scholar
  6. 6.
    Kim RJ, Rutstein RM (2010) Impact of antiretroviral therapy on growth, body composition and metabolism in pediatric HIV patients. Paediatr Drugs 12:187–199PubMedCrossRefGoogle Scholar
  7. 7.
    Nachman SA, Chernoff MC, Gona P, Van Dyke RB, Dankner WM, Seage GR III, Oleske J, Williams PL, PACTG 219C Team (2009) Incidence of non-infectious conditions in perinatally HIV-infected children and adolescents in the HAART era. Arch Pediatr Adolesc Med 163:164–171PubMedCrossRefGoogle Scholar
  8. 8.
    Jao J, Wyatt CM (2010) Antiretroviral medications: adverse effects on the kidney. Ad Chronic Kidney Dis 17:72–82CrossRefGoogle Scholar
  9. 9.
    Fine DM, Perazella MA, Lucas GM, Atta MG (2008) Kidney biopsy in HIV: beyond HIV-associated nephropathy. Am J Kidney Dis 51:504–514PubMedCrossRefGoogle Scholar
  10. 10.
    Kimmel PL, Barisoni L, Kopp JB (2003) Pathogenesis and treatment of HIV-associated renal diseases: lessons from clinical and animal studies, molecular pathological correlations, and genetic investigations. Ann Intern Med 139:214–216PubMedGoogle Scholar
  11. 11.
    McCulloch MI, Ray PE (2008) Kidney disease in HIV-positive children. Semin Nephrol 28:585–594PubMedCrossRefGoogle Scholar
  12. 12.
    Ray PE, Xu L, Rakusan T, Liu X (2004) A 20-year history of childhood HIV-associated nephropathy. Pediatr Nephrol 19:1075–1092PubMedCrossRefGoogle Scholar
  13. 13.
    Cohen SD, Kimmel PL (2008) Immune complex renal disease and human immunodeficiency virus infection. Semin Nephrol 28:535–544PubMedCrossRefGoogle Scholar
  14. 14.
    Motala AI, Mogotlane L, Goetsch S (2009) Renal pathology in the HIV-positive child: from nephrosis to nephritis and everything in between. Diagnostic Histopathol 15:232–240CrossRefGoogle Scholar
  15. 15.
    Pardo V, Meneses R, Ossa L, Jaffe DJ, Strauss J, Roth D, Bourgoigne JJ (1987) AIDS-related glomerulopathy: occurrence in specific risk groups. Kidney Int 31:1167–1173PubMedCrossRefGoogle Scholar
  16. 16.
    Connor E, Gupta S, Joshi V, DiCarlo F, Offenberger J, Minnefor J, Uy C, Oleske J, Ende N (1988) Acquired immunodeficiency syndrome-associated renal disease in children. J Pediatr 113:39–44PubMedCrossRefGoogle Scholar
  17. 17.
    Strauss J, Abitbol C, Zilleruelo G, Scott G, Paredes A, Malaga S, Montaner B, Mitchell C, Parks W, Pardo V (1989) Renal disease in children with the acquired immunodeficiency syndrome. N Engl J Med 321:625–630PubMedCrossRefGoogle Scholar
  18. 18.
    Chaparro AI, Mitchell CD, Abitbol CL, Wilkinson JD, Baldarrago G, Lopez E, Zilleruelo G (2008) Proteinuria in children infected with the human immunodeficiency virus. J Pediatr 152:844–849PubMedCrossRefGoogle Scholar
  19. 19.
    Cohen SD, Kimmel PL (2009) Renal biopsy is necessary for the diagnosis of HIV-associated renal diseases. Nat Clin Pract Nephrol 5:22–23PubMedCrossRefGoogle Scholar
  20. 20.
    Andiman WA, Chernoff MC, Mitchell C, Purswani M, Oleske J, Williams PL, Spiege H, Gona P, Seage GR III, PACTG iDACS 617 Study Team (2009) Incidence of persistent renal dysfunction in human immunodeficiency virus-infected children: associations with the use of antiretrovirals, and other nephrotoxic medications and risk factors. Pediatr Infect Dis J 28:619–625PubMedCrossRefGoogle Scholar
  21. 21.
    Brown EG, Wood L, Wood S (1999) The medical dictionary for regulatory activities (MedRA). Drug Saf 20:109–117PubMedCrossRefGoogle Scholar
  22. 22.
    Post FA, Campbell LJ, Hamzah L, Collins L, Jones R, Siwani R, Johnson L, Fisher M, Holt SG, Bhagani S, Frankel AH, Wilkins E, Ainsworth JG, Larbalestier N, Macallan DC, Banerjee D, Bailey G, Thuraisingham RG, Donohoe P, Hendry PM, Hilton RM, Edwards SG, Hangartner R, Howie AJ, Connolly JO, Easterbrook PJ (2008) Predictors of renal outcome in HIV-associated nephropathy. Clin Infect Dis 46:1282–1289PubMedCrossRefGoogle Scholar
  23. 23.
    Centers for Disease Control and Prevention (1994) 1994 revised classification system for human immunodeficiency virus infection in children less than 13 years of age. Official authorized addenda: human immunodeficiency virus infection codes and official guidelines for coding and reporting ICD-9-CM. MMWR Recomm Rep 43:1–19Google Scholar
  24. 24.
    Cole SR, Napravnik S, Mugavero MJ, Lau B, Eron JJ, Saag MS (2010) Copy-years viremia as a measure of cumulative human immunodeficiency virus viral burden. Am J Epidemiol 171:198–205PubMedCrossRefGoogle Scholar
  25. 25.
    Brogly S, Williams P, Seage GR III, Oleske J, Van Dyke R, McIntosh K, PACTG 219C Team (2005) Antiretroviral treatment in pediatric HIV infection in the United States: from clinical trials to clinical practice. JAMA 293:2213–2220PubMedCrossRefGoogle Scholar
  26. 26.
    Rao TK, Filippone EJ, Nicastri AD, Landesman SH, Frank E, Chen CK, Friedman EA (1984) Associated focal and segmental glomerulosclerosis in the acquired immunodeficiency syndrome. N Engl J Med 310:669–673PubMedCrossRefGoogle Scholar
  27. 27.
    Naicker S, Han TM, Fabian J (2006) HIV/AIDS—dominant player in chronic kidney disease. Ethn Dis 16(S2):56–60Google Scholar
  28. 28.
    Ray PE (2009) Taking a hard look at the pathogenesis of childhood HIV-associated nephropathy. Pediatr Nephrol 24:2109–2119PubMedCrossRefGoogle Scholar
  29. 29.
    Singh KH, Baldree LA, McKenney DW, Hogan SL, Jennette JC (2000) Idiopathic collapsing glomerulopathy in children. Clin Nephrol 14:132–137Google Scholar
  30. 30.
    Albaqumi M, Barisoni L (2008) Current views on collapsing glomerulopathy. J Am Soc Nephrol 19:1276–1281PubMedCrossRefGoogle Scholar
  31. 31.
    Bruggeman LA, Nelson PJ (2009) Controversies in the pathogenesis of HIV-associated renal diseases. Nat Rev Nephrol 5:574–581PubMedCrossRefGoogle Scholar
  32. 32.
    Haas M, Kaul S, Eustace JA (2005) HIV-associated immune complex glomerulonephritis with “lupus-like” features: a clinicopathologic study of 14 cases. Kidney Int 67:1381–1390PubMedCrossRefGoogle Scholar
  33. 33.
    Gindea S, Schwartzman J, Herlitz LC, Rosenberg M, Abadi J, Putterman C (2010) Proliferative glomerulonephritis in lupus patients with human immunodeficiency virus infection: a difficult clinical challenge. Semin Arthritis Rheum 40:201–209PubMedCrossRefGoogle Scholar
  34. 34.
    Beaufils H, Jouanneau C, Katlama C, Sazdovitch V, Hauw JJ (1995) HIV-associated IgA nephropathy—a post-mortem study. Nephrol Dial Transplant 10:35–38PubMedGoogle Scholar
  35. 35.
    Nochy D, Glotz D, Dosquet P, Pruna A, Guttier C, Weiss L, Hinglais N, Idatte JM, Mery JP, Kazatchkine M (1993) Renal disease associated with HIV infection: a multicentric study of 60 patients from Paris hospitals. Nephrol Dial Transplant 8:11–19PubMedGoogle Scholar
  36. 36.
    Trachtman H, Gauthier B, Vinograd A, Valderrama E (1991) IgA nephropathy in a child with human immunodeficiency virus type 1 infection. Pediatr Nephrol 5:724–726PubMedCrossRefGoogle Scholar
  37. 37.
    Alarcon-Zinta A, Salas A, Anton E, Morey A, Munar MA, Losada P, Martinez J (2000) Membranous glomerulonephritis with nephrotic syndrome in an HIV-positive patient—remarkable remission with triple therapy. Nephrol Dial Transplant 15:1097–1098CrossRefGoogle Scholar
  38. 38.
    Nebuloni M, Barbiano di Belgiojoso G, Gendirini A, Tosoni A, Raini LN, Heidempergher M, Zerbi P, Vago L (2009) Glomerular lesions in HIV positive patients: a 20-year biopsy experience from Northern Italy. Clin Nephrol 72:38–45PubMedGoogle Scholar
  39. 39.
    Gerntholtz TE, Goetsch SJ, Katz I (2006) HIV-related nephropathy: a South African perspective. Kidney Int 69:1885–1891PubMedCrossRefGoogle Scholar
  40. 40.
    Zerhouni-Layachi B, Hussain M, Ross MJ, Marras D, Sunamoto M, Liu X, Klotman PE, Klotman ME (2006) Dual tropism of HIV-1 envelopes derived from renal tubular epithelial cells of patients with HIV-associated nephropathy. AIDS 20:621–624PubMedCrossRefGoogle Scholar
  41. 41.
    Ross MJ, Fan C, Ross MD, Chu TH, Shi Y, Kaufman L, Zhang W, Klotman ME, Klotman PE (2006) HIV-1 infection initiates an inflammatory cascade in human renal tubular epithelial cells. J Acquir Immune Defic Syndr 42:1–11PubMedCrossRefGoogle Scholar
  42. 42.
    Winston JA (2010) HIV and CKD epidemiology. Ad Chronic Kidney Dis 17:19–25CrossRefGoogle Scholar
  43. 43.
    Estrella M, Fine DM, Gallant JE, Rahman MH, Nagajothi N, Racusen LC, Scheel PJ, Atta MG (2006) HIV type 1 RNA level as a clinical indicator of renal pathology in HIV-infected patients. Clin Infect Dis 43:377–380PubMedCrossRefGoogle Scholar
  44. 44.
    Bostrom MA, Freedman BI (2010) The spectrum of MYH9-associated nephropathy. Clin J Am Soc Nephrol 5:1107–1113PubMedCrossRefGoogle Scholar
  45. 45.
    Nelson GW, Freedman BI, Bowden DW, Langefeld CD, An P, Hicks PJ, Bostrom MA, Johnson RC, Kopp JB, Winkler CA (2010) Dense mapping of MYH9 localizes the strongest kidney disease associations to the region of introns 13 to 15. Hum Mol Genet 19:1805–1815PubMedCrossRefGoogle Scholar
  46. 46.
    Genovese G, Friedman DJ, Ross MD, Lecordier L, Uzureau P, Freedman BI, Bowden DW, Langefeld CD, Oleksyk TK, Uscinski Knob AL, Bernhardy AJ, Hicks PJ, Nelson GW, Vanhollebeke B, Winkler CA, Kopp JB, Pays E, Pollak MR (2010) Association of trypanolytic ApoL1 variants with kidney disease in African Americans. Science 329:841–845PubMedCrossRefGoogle Scholar
  47. 47.
    Tzur S, Rosset S, Shemer R, Yudkovsky G, Selig S, Tarekegn A, Bekele E, Bradman N, Wasser WG, Behar GM, Skorecki K (2010) Missense mutations in the APOL1 gene are highly associated with end stage kidney disease risk previously attributed to the MYH9 gene. Hum Genet 128:345–350PubMedCrossRefGoogle Scholar
  48. 48.
    Rachakonda AK, Kimmel PL (2010) CKD in HIV-infected patients other than HIV-associated nephropathy. Adv Chronic Kidney Dis 17:83–93PubMedCrossRefGoogle Scholar

Copyright information

© IPNA 2012

Authors and Affiliations

  • Murli U. Purswani
    • 1
  • Miriam C. Chernoff
    • 2
  • Charles D. Mitchell
    • 3
  • George R. SeageIII
    • 2
    • 4
  • Gaston Zilleruelo
    • 5
  • Carolyn Abitbol
    • 5
  • Warren A. Andiman
    • 6
  • Kathleen A. Kaiser
    • 7
  • Hans Spiegel
    • 8
  • James M. Oleske
    • 9
  • The IMPAACT 219/219C Study Team
  1. 1.Department of Pediatrics, Bronx-Lebanon Hospital CenterAlbert Einstein College of MedicineBronxUSA
  2. 2.Center for Biostatistics in AIDS Research, Harvard School of Public HealthBostonUSA
  3. 3.Division of Infectious Diseases and Immunology, Department of Pediatrics, Batchelor Children’s Research InstituteUniversity of Miami Miller School of MedicineMiamiUSA
  4. 4.Department of EpidemiologyHarvard School of Public HealthBostonUSA
  5. 5.Division of Pediatric Nephrology, Department of PediatricsUniversity of Miami Miller School of MedicineMiamiUSA
  6. 6.Departments of Pediatrics and EpidemiologyYale University School of Medicine and School of Public HealthNew HavenUSA
  7. 7.Frontier Science and Technology Research FoundationAmherstUSA
  8. 8.Microbicide Research Branch, Prevention Science Program, Division of AIDS (DAIDS), National Institute of Allergy and Infectious Diseases (NIAID)BethesdaUSA
  9. 9.Department of PediatricsUniversity of Medicine and Dentistry of New Jersey, New Jersey Medical SchoolNJUSA

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