This document discusses HIV and its impact on the kidneys. It includes information from a nephrologist and clinical studies showing: 1) HIV can cause kidney disease, most notably HIV-associated nephropathy (HIVAN), which disproportionately affects African Americans. 2) Early studies from the pre-HAART era in the 1980s-1990s showed high rates of kidney disease and failure in people with HIV. 3) Later studies from the HAART era in the 2000s found lower rates of new kidney disease but higher overall prevalence, suggesting antiretroviral drugs may be improving outcomes for some but also contributing to kidney issues over the long term.

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

7. October 2, 1985

8. 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;

9. 1995
Selik RM, et al. J AIDS 2002; 29: 378-387.

14. 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)

15. 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.

16. Compared to the
uninfected ESRD was
7x more likely
w i t hou t AIDS a nd
16x more likely
w ith AIDS

17. ESRD increased
20% in the
HAART era
des pi t e s i g n i fi c an t
decrease in
incident CKD

18. are the increased
renal,
hepatic and
cardiac
disease due to
drugs or
bugs?

21. 1995 to 2001: admission rate
for cardio- or cerebro-vascular disease
fell from 1.7 to 0.9
admits per 100 patient years

22. 1995 to 2001: the death rate
fell from 21.3 to
5.0 per 100 patient years

27. the adjusted relative risk
of a myocardial infarction
was 1.15 / year
of exposure to
protease inhibitors

29. • 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

31. stopped after
Sixteen
Months

35. the specific way that
drugs are used can
determine the outcome
don’t trust the
rearview mirror

38. 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

40. 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

44. 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

45. The only cause or ESRD more
associated with African descent is
Sickle
Cell
Anemia

46. Definitive diagnosis

47. Definitive diagnosis

48. 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

49. 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

50. 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

51. 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

52. 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

53. 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

54. 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%

55. 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)

56. Diagnosis: echodensity does

57. 0 I
III
II

58. Diagnosis: echodensity does

59. 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)

60. 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)

61. Treatment: ART/HAART
Nagajothi, et al. ASN 2005. Renal Week. Philadelphia, PA Abstract #TH-FC041.
Lucas GM, et al. AIDS 2004; 20:541-546.

62. Treatment: Steroids
Eustace JA, et al. Kidney International (2000) 58, 1253–1260;

63. Schwartz EJ. J Am Soc Nephrol 16: 2412-2420, 2005.

64. Schwartz EJ. J Am Soc Nephrol 16: 2412-2420, 2005.

65. 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.

66. The changing nature of HIV
renal disease
• Other HIV Nephropathies
• Importance and frequency of proteinuria
• Drug induced toxicity

67. 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.

68. 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.

69. 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.

70. 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