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HIV and the Kidney 2009
HIV and the Kidney 2009
HIV and the Kidney 2009
HIV and the Kidney 2009
HIV and the Kidney 2009
HIV and the Kidney 2009
HIV and the Kidney 2009
HIV and the Kidney 2009
HIV and the Kidney 2009
HIV and the Kidney 2009
HIV and the Kidney 2009
HIV and the Kidney 2009
HIV and the Kidney 2009
HIV and the Kidney 2009
HIV and the Kidney 2009
HIV and the Kidney 2009
HIV and the Kidney 2009
HIV and the Kidney 2009
HIV and the Kidney 2009
HIV and the Kidney 2009
HIV and the Kidney 2009
HIV and the Kidney 2009
HIV and the Kidney 2009
HIV and the Kidney 2009
HIV and the Kidney 2009
HIV and the Kidney 2009
HIV and the Kidney 2009
HIV and the Kidney 2009
HIV and the Kidney 2009
HIV and the Kidney 2009
HIV and the Kidney 2009
HIV and the Kidney 2009
HIV and the Kidney 2009
HIV and the Kidney 2009
HIV and the Kidney 2009
HIV and the Kidney 2009
HIV and the Kidney 2009
HIV and the Kidney 2009
HIV and the Kidney 2009
HIV and the Kidney 2009
HIV and the Kidney 2009
HIV and the Kidney 2009
HIV and the Kidney 2009
HIV and the Kidney 2009
HIV and the Kidney 2009
HIV and the Kidney 2009
HIV and the Kidney 2009
HIV and the Kidney 2009
HIV and the Kidney 2009
HIV and the Kidney 2009
HIV and the Kidney 2009
HIV and the Kidney 2009
HIV and the Kidney 2009
HIV and the Kidney 2009
HIV and the Kidney 2009
HIV and the Kidney 2009
HIV and the Kidney 2009
HIV and the Kidney 2009
HIV and the Kidney 2009
HIV and the Kidney 2009
HIV and the Kidney 2009
HIV and the Kidney 2009
HIV and the Kidney 2009
HIV and the Kidney 2009
HIV and the Kidney 2009
HIV and the Kidney 2009
HIV and the Kidney 2009
HIV and the Kidney 2009
HIV and the Kidney 2009
HIV and the Kidney 2009
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HIV and the Kidney 2009

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  • Methods:
    AA participants in 2 Baltimore-based cohort studies were included in this analysis: the


  • Johns Hopkins HIV Cohort, a clinic-based cohort of HIV(+) participants, and the ALIVE study, a

  • community-based cohort of HIV(-) and HIV(+) injection drug users. ESRD/RRT was determined by

  • matching participant identifiers with the US Renal Data System. Standardized incidence ratios (SIR)

  • and poison regression were used to compare to age-matched AA in the general population and to

  • assess for temporal trends, respectively. We compared ESRD/RRT trends with those of chronic

  • kidney disease (CKD) incidence and prevalence. CKD was defined as GFR<60ml/min/1.73m2 for > 3

  • months.


  • Results:
    RRT was initiated in 24 HIV(-) subjects during 13,415 person-years (PY) of follow-up, 51


  • HIV(+) participants without AIDS during 10,780 PY, and 125 participants with AIDS during 9,833 PY,

  • corresponding to SIRs of 2.3 (95% CI 1.5-3.4), 6.9 (95% CI 5.1-9.0), and 16.1 (95% CI 13.4-19.2),

  • respectively. In HIV(+) African American participants RRT incidences were 5.8 and 9.7 per 1,000 PY

  • in the pre-HAART and HAART eras, respectively (adjusted incidence rate ratio 1.2, 95% 0.8-1.9). In

  • supplementary analyses, we found that, while CKD incidence declined significantly in the HAART era

  • compared to the pre-HAART era, CKD period prevalence increased.


  • Conclusions:
    The ESRD/RRT rate is high in HIV(+) AAs and has not decreased appreciably in this


  • cohort with the widespread use of HAART. While CKD incidence has declined significantly in the

  • HAART era, CKD prevalence has increased as patients live longer.

  • In this population the incidence of CKD is decreasing. TDF use is increasing.










  • VA study which raised the question does haart reduce mortality despite increasing metabolic abnormalities






  • retrospective study









  • 36,766 who received care at VA from 93-2001




















  • DAD study prospective observational of 23,000 11 cohorts europe and NA

  • looked at association of AMI and exposure to nonNucs and PIs

  • better vetted events than VA study


























































  • Average GFR > 100

  • CD4 250

  • No patients on ART

  • No outcome data



  • Transcript

    • 1. Joel M. Topf, MD Clinical Nephrologist St John Hospital 248.470.8163 http:pbfluids.blogspot.com
    • 2. HIV and the Kidney Joel M. Topf, MD Clinical Nephrologist St John Hospital 248.470.8163 http:pbfluids.blogspot.com
    • 3. HIV and the Kidney 2.0 Joel M. Topf, MD Clinical Nephrologist St John Hospital 248.470.8163 http:pbfluids.blogspot.com
    • 4. October 2, 1985
    • 5. November 7, 1991 quot;I think we sometimes think only gay people can get it; it's not going to happen to me. And here I am saying that it can happen to anybody, even me, Magic Johnson.quot;
    • 6. 1995 Selik RM, et al. J AIDS 2002; 29: 378-387.
    • 7. Progression to ESRD Pre-HAART vs. HAART Era • JHHC – clinic-based, all HIV positive – N = 3,876 • ALIVE – community-based, all IDU, both HIV positive and negative – N = 2,379 • Median age: 37 y • Female: 32% • IDU: 70% • HIV negative: 28% • Log HIV RNA: 4.4 (median value) • CD4: 287 (median value)
    • 8. Occurrence rate Univariate RR Adjusted RR* Outcome (per 1000 PYs) (95% CI) (95% CI) Incidence of chronic kidney disease Pre-HAART era 22.2 1.0 1.0 HAART era 16.0 0.72 (0.55-0.94) 0.64 (0.49-0.85) Death with chronic kidney disease prior to dialysis Pre-HAART era 8.6 1.0 1.0 HAART era 5.8 0.67 (0.44-1.04) 0.54 (0.35-0.84) Period prevalence of chronic kidney disease Pre-HAART era 47.7 1.0 1.0 HAART era 69.3 1.45 (1.11-1.90) 1.37 (1.05-1.80) Incident ESRD/RRT Pre-HAART era 5.9 1.0 1.0 HAART era 9.4 1.59 (0.98-2.59) 1.46 (0.89-2.37) Incident ESRD/RRT or death with chronic kidney disease prior to dialysis Pre-HAART era 14.6 1.0 1.0 HAART era 15.3 1.05 (0.76-1.44) 0.91 (0.66-1.25) *Adjusted for age and AIDS status Lucas, et al. CROI 2007 poster #829.
    • 9. Compared to the uninfected ESRD was 7x more likely w i t hou t AIDS a nd 16x more likely w ith AIDS
    • 10. ESRD increased 20% in the HAART era des pi t e s i g n i fi c an t decrease in incident CKD
    • 11. are the increased renal, hepatic and cardiac disease due to drugs or bugs?
    • 12. 1995 to 2001: admission rate for cardio- or cerebro-vascular disease fell from 1.7 to 0.9 admits per 100 patient years
    • 13. 1995 to 2001: the death rate fell from 21.3 to 5.0 per 100 patient years
    • 14. the adjusted relative risk of a myocardial infarction was 1.15 / year of exposure to protease inhibitors
    • 15. • patients with CD4 > 350 were enrolled • randomized to – continuous HAART (viral suppression group) – interrupted HAART, drug vacation when CD4 > 350 and resumption when CD4 less than 250 until CD4 is over 350 • Open label • end-point: OI or death • power analysis indicated the study would last 6 years to accrue 910 end- points
    • 16. stopped after Sixteen Months
    • 17. the specific way that drugs are used can determine the outcome don’t trust the rearview mirror
    • 18. Freq of HIV at initiation of dialysis 0 0.01 0.02 0.03 0.04 0.05 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004
    • 19. HIVAN • first readily identified renal manifestation of HIV • rapidly progressing renal failure • heavy proteinuria • usually – low CD4 – high viral load • BP tends to be low • large echogenic kidneys 31
    • 20. HIVAN. a black person disease. • United States – African Americans 12.2 times more likely to develop HIVAN than whites – Among those with ESRD secondary to HIV/AIDS: 88.4% African American • Europe – France: 97/102 with HIVAN were black – London 17/17 with HIVAN were black – Switzerland 239 autopsies with dx of AIDS • 1 case of HIVAN in a black individual
    • 21. The only cause or ESRD more associated with African descent is Sickle Cell Anemia
    • 22. Definitive diagnosis
    • 23. Definitive diagnosis
    • 24. HIVAN Pathophysiology HIV-1 • HIV infects podocytes • HIV infects tubular epithelial cells – Loss of differentiation markers – Loss of differentiation markers – Loss of foot processes – Apoptosis – Immature forms of collagen are expressed – Proliferation Capillary loop collapse Tubular degeneration and regeneration and microcyst formation
    • 25. the epidemiology is in doubt • HIVAN is found in 40-60% of renal biopsies done for cause • Autopsy study of organs from HIV- infected persons in Texas found that the overall prevalence of HIVAN was 6.9% • Screening protocols for HIVAN based on biopsies in HIV-infected patients with >1.5 g/day of proteinuria have found an overall prevalence of 3.5%. Shahinian V, Rajaraman S, et al. Am J Kidney Dis. 2000; 35(5):884-8 Ahuja TS, Borucki M, et al. Am J Nephrol. 1999 19(6):655-9
    • 26. Kidney International 2006; 69: 2243-2250. 615 HIV+ Black South Africans No proteinuria + Proteinuria 577 (94%) 38 (6%) 90 patients tested for 487 No further 10 lost to follow-up 23 kidney biopsies Microalbumin testing 5 refused consent for biopsy 32 had Microalbuminuria 19 HIVAN 36% 7 had persistant microalbuminuria (8%) 7 kidney biopsies 6 HIVAN
    • 27. Kidney International 2006; 69: 2243-2250. 615 HIV+ Black South Africans No proteinuria + Proteinuria 577 (94%) 38 (6%) 90 patients tested for 487 No further 10 lost to follow-up 23 kidney biopsies Microalbumin testing 5 refused consent for biopsy 32 had Microalbuminuria 19 HIVAN 36% 83% 7 had persistant microalbuminuria (8%) 7 kidney biopsies 6 HIVAN
    • 28. Kidney International 2006; 69: 2243-2250. 615 HIV+ Black South Africans No proteinuria + Proteinuria 577 (94%) 38 (6%) 90 patients tested for 487 No further 10 lost to follow-up 23 kidney biopsies Microalbumin testing 5 refused consent for biopsy 32 had Microalbuminuria 19 HIVAN 36% 83% 7 had persistant microalbuminuria (8%) 7 kidney biopsies 6 HIVAN
    • 29. Kidney International 2006; 69: 2243-2250. 615 HIV+ Black South Africans No proteinuria + Proteinuria 577 (94%) 38 (6%) 90 patients tested for 487 No further 10 lost to follow-up 23 kidney biopsies Microalbumin testing 5 refused consent for biopsy 32 had Microalbuminuria 19 HIVAN 36% 83% 7 had persistant microalbuminuria (8%) 7 kidney biopsies 6 HIVAN
    • 30. Kidney International 2006; 69: 2243-2250. 615 HIV+ Black South Africans No proteinuria + Proteinuria 577 (94%) 38 (6%) 90 patients tested for 487 No further 10 lost to follow-up 23 kidney biopsies Microalbumin testing 5 refused consent for biopsy 32 had Microalbuminuria 19 HIVAN 36% 83% 7 had persistant microalbuminuria (8%) 7 kidney biopsies 6 HIVAN 86%
    • 31. Diagnosis: Size doesn’t matter HIVAN No HIVAN Ave. Length 11.3 cm 11.5 cm Sensitivity (>12 cm) 28% (12-49) Specificity (>12 cm) 75% (58-88) PPV (>12 cm) 44% (20-70) NPV (>12 cm) 60% (44-74)
    • 32. Diagnosis: echodensity does
    • 33. 0 I III II
    • 34. Diagnosis: echodensity does
    • 35. Diagnosis: echodensity does Operating Characteristic Grade II/III Grade III Sensitivity 96% (80-100) 40% (21-61) Specificity 28% (12-49) 95% (82-99) PPV 57% (41-72) 83% (52-98) NPV 95% (75-100) 70% (55-82)
    • 36. Diagnosis: echodensity does Operating Characteristic Grade II/III Grade III Sensitivity 96% (80-100) 40% (21-61) Specificity 28% (12-49) 95% (82-99) PPV 57% (41-72) 83% (52-98) NPV 95% (75-100) 70% (55-82)
    • 37. Treatment: ART/HAART Nagajothi, et al. ASN 2005. Renal Week. Philadelphia, PA Abstract #TH-FC041. Lucas GM, et al. AIDS 2004; 20:541-546.
    • 38. Treatment: Steroids Eustace JA, et al. Kidney International (2000) 58, 1253–1260;
    • 39. Schwartz EJ. J Am Soc Nephrol 16: 2412-2420, 2005.
    • 40. Schwartz EJ. J Am Soc Nephrol 16: 2412-2420, 2005.
    • 41. Hispanic 18% African American 50% White 30% Race/ethnicity of persons (including children) with HIV/AIDS diagnosed during 2004 (N = 38,730) CDC. HIV/AIDS Surveillance Report, 2004. Vol. 16. Atlanta: US16: 2412-2420, 2005. Schwartz EJ. J Am Soc Nephrol Department of Health and Human Services, CDC: 2005:1–46.
    • 42. The changing nature of HIV renal disease • Other HIV Nephropathies • Importance and frequency of proteinuria • Drug induced toxicity
    • 43. HIV+ renal biopsy Findings 42 HIVAN 13 Immune complex GN 8 Membranous nephropathy 6 Diabetic glomerulopathy 5 Membranoproliferative GN 5 Hypertensive nephrosclerosis 3 Interstitial nephritis 2 Amyloid 1 FSGS without HIVAN 1 Minimal change disease 1 Acute renal failure related to indinavir 1 IgA nephropathy 1 Chronic pyelonephritis Szczech LA, et al. Kidney Int. 2004 Sep;66(3):1145-52.
    • 44. HIV+ renal biopsy Findings 42 HIVAN 13 Immune complex GN 8 Membranous nephropathy 6 Diabetic glomerulopathy 5 Membranoproliferative GN 5 Hypertensive nephrosclerosis HIVAN 47% Non-HIVAN 3 Interstitial nephritis 53% 2 Amyloid 1 FSGS without HIVAN 1 Minimal change disease 1 Acute renal failure related to indinavir 1 IgA nephropathy 1 Chronic pyelonephritis Szczech LA, et al. Kidney Int. 2004 Sep;66(3):1145-52.
    • 45. HIV+ renal biopsy Findings Non-HIVAN vs HIVAN 42 HIVAN White 5% vs 0% 13 Immune complex GN Hepatitis B 27% vs 10% 8 Membranous nephropathy Hepatitis C 61% vs 41% 6 Diabetic glomerulopathy 5 Membranoproliferative GN Higher CD4 287 vs 187 5 Hypertensive nephrosclerosis HIVAN Hypertension 51% vs 74% 47% Non-HIVAN 3 Interstitial nephritis 53% Lower Cr 2.6 vs 4.7 2 Amyloid 1 FSGS without HIVAN 1 Minimal change disease 1 Acute renal failure related to indinavir 1 IgA nephropathy 1 Chronic pyelonephritis Szczech LA, et al. Kidney Int. 2004 Sep;66(3):1145-52.
    • 46. HIV+ renal biopsy Findings Non-HIVAN vs HIVAN 42 HIVAN White 5% vs 0% 13 Immune complex GN Hepatitis B 27% vs 10% 8 Membranous nephropathy Hepatitis C 61% vs 41% 6 Diabetic glomerulopathy 5 Membranoproliferative GN Higher CD4 287 vs 187 5 Hypertensive nephrosclerosis HIVAN Hypertension 51% vs 74% 47% Non-HIVAN 3 Interstitial nephritis 53% Lower Cr 2.6 vs 4.7 2 Amyloid 1 FSGS without HIVAN 1 Minimal change disease 1 Acute renal failure related to indinavir 1 IgA nephropathy 1 Chronic pyelonephritis “…[in] lesions other than HIVAN, the use of anti

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