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Joel M. Topf, MD
     Clinical Nephrologist
           St John Hospital
              248.470.8163
http:pbfluids.blogspot....
HIV and the
Kidney
           Joel M. Topf, MD
       Clinical Nephrologist
             St John Hospital
                ...
HIV and the
Kidney 2.0
           Joel M. Topf, MD
       Clinical Nephrologist
             St John Hospital
            ...
October 2, 1985
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 ...
1995




       Selik RM, et al. J AIDS 2002; 29: 378-387.
Progression to ESRD
  Pre-HAART vs. HAART Era
• JHHC – clinic-based, all HIV positive
  – N = 3,876
• ALIVE – community-ba...
Occurrence rate   Univariate RR      Adjusted RR*
Outcome                                 (per 1000 PYs)     (95% CI)     ...
Compared to the
 uninfected ESRD was
7x more likely
 w i t hou t AIDS a nd
16x more likely
     w ith AIDS
ESRD increased
  20% in the
  HAART era
des pi t e s i g n i fi c an t
decrease in
incident CKD
are the increased
renal,
hepatic and
cardiac
disease due to


     drugs or
       bugs?
1995 to 2001: admission rate
for cardio- or cerebro-vascular disease

fell from 1.7 to 0.9
admits per 100 patient years
1995 to 2001: the death rate

fell from 21.3 to
5.0 per 100 patient years
the adjusted relative risk
of a myocardial infarction
was 1.15 / year
of exposure to
protease inhibitors
• patients with CD4 > 350 were enrolled
• randomized to
  – continuous HAART (viral suppression
    group)
  – interrupted...
stopped after
Sixteen
Months
the specific way that
drugs are used can
determine the outcome
don’t trust the
rearview mirror
Freq of HIV at initiation of dialysis




       0
             0.01
                    0.02
                            ...
HIVAN
• first readily identified renal
  manifestation of HIV
• rapidly progressing renal failure
• heavy proteinuria
• us...
HIVAN. a black person disease.
• United States
  – African Americans 12.2 times more likely to
    develop HIVAN than whit...
The only cause or ESRD more
associated with African descent is

         Sickle
        Cell
        Anemia
Definitive diagnosis
Definitive diagnosis
HIVAN Pathophysiology
                               HIV-1

• HIV infects podocytes           • HIV infects tubular
      ...
the epidemiology is in doubt
• HIVAN is found in 40-60% of renal
  biopsies done for cause
• Autopsy study of organs from ...
Kidney International 2006; 69: 2243-2250.

                                                        615 HIV+
              ...
Kidney International 2006; 69: 2243-2250.

                                                        615 HIV+
              ...
Kidney International 2006; 69: 2243-2250.

                                                        615 HIV+
              ...
Kidney International 2006; 69: 2243-2250.

                                                        615 HIV+
              ...
Kidney International 2006; 69: 2243-2250.

                                                        615 HIV+
              ...
Diagnosis: Size doesn’t matter

                                      HIVAN         No HIVAN

               Ave. Length  ...
Diagnosis: echodensity does
0    I




     III
II
Diagnosis: echodensity does
Diagnosis: echodensity does



Operating
Characteristic     Grade II/III      Grade III
Sensitivity      96% (80-100)     ...
Diagnosis: echodensity does



Operating
Characteristic     Grade II/III      Grade III
Sensitivity      96% (80-100)     ...
Treatment: ART/HAART




    Nagajothi, et al. ASN 2005. Renal Week. Philadelphia, PA Abstract #TH-FC041.
                ...
Treatment: Steroids




        Eustace JA, et al. Kidney International (2000) 58, 1253–1260;
Schwartz EJ. J Am Soc Nephrol 16: 2412-2420, 2005.
Schwartz EJ. J Am Soc Nephrol 16: 2412-2420, 2005.
Hispanic
              18%




                                                                       African American
   ...
The changing nature of HIV
        renal disease


• Other HIV Nephropathies
• Importance and frequency of proteinuria
• D...
HIV+ renal biopsy Findings
42 HIVAN
13 Immune complex GN
 8 Membranous nephropathy
 6 Diabetic glomerulopathy
 5 Membranop...
HIV+ renal biopsy Findings
42 HIVAN
13 Immune complex GN
 8 Membranous nephropathy
 6 Diabetic glomerulopathy
 5 Membranop...
HIV+ renal biopsy Findings                                    Non-HIVAN vs HIVAN
42 HIVAN
                                ...
HIV+ renal biopsy Findings                                    Non-HIVAN vs HIVAN
42 HIVAN
                                ...
The Kidney and HIV
The Kidney and HIV
The Kidney and HIV
The Kidney and HIV
The Kidney and HIV
The Kidney and HIV
The Kidney and HIV
The Kidney and HIV
The Kidney and HIV
The Kidney and HIV
The Kidney and HIV
The Kidney and HIV
The Kidney and HIV
The Kidney and HIV
The Kidney and HIV
The Kidney and HIV
The Kidney and HIV
The Kidney and HIV
The Kidney and HIV
The Kidney and HIV
The Kidney and HIV
The Kidney and HIV
The Kidney and HIV
The Kidney and HIV
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The Kidney and HIV

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The Kidney and HIV

  1. 1. Joel M. Topf, MD Clinical Nephrologist St John Hospital 248.470.8163 http:pbfluids.blogspot.com
  2. 2. HIV and the Kidney Joel M. Topf, MD Clinical Nephrologist St John Hospital 248.470.8163 http:pbfluids.blogspot.com
  3. 3. HIV and the Kidney 2.0 Joel M. Topf, MD Clinical Nephrologist St John Hospital 248.470.8163 http:pbfluids.blogspot.com
  4. 4. October 2, 1985
  5. 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. 6. 1995 Selik RM, et al. J AIDS 2002; 29: 378-387.
  7. 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. 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. 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. 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. 11. are the increased renal, hepatic and cardiac disease due to drugs or bugs?
  12. 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. 13. 1995 to 2001: the death rate fell from 21.3 to 5.0 per 100 patient years
  14. 14. the adjusted relative risk of a myocardial infarction was 1.15 / year of exposure to protease inhibitors
  15. 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. 16. stopped after Sixteen Months
  17. 17. the specific way that drugs are used can determine the outcome don’t trust the rearview mirror
  18. 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. 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. 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. 21. The only cause or ESRD more associated with African descent is Sickle Cell Anemia
  22. 22. Definitive diagnosis
  23. 23. Definitive diagnosis
  24. 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. 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. 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. 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. 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. 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. 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. 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. 32. Diagnosis: echodensity does
  33. 33. 0 I III II
  34. 34. Diagnosis: echodensity does
  35. 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. 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. 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. 38. Treatment: Steroids Eustace JA, et al. Kidney International (2000) 58, 1253–1260;
  39. 39. Schwartz EJ. J Am Soc Nephrol 16: 2412-2420, 2005.
  40. 40. Schwartz EJ. J Am Soc Nephrol 16: 2412-2420, 2005.
  41. 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. 42. The changing nature of HIV renal disease • Other HIV Nephropathies • Importance and frequency of proteinuria • Drug induced toxicity
  43. 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. 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. 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. 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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