HIV and the Kidney 2009

Joel M. Topf, MD Clinical Nephrologist St John Hospital 248.470.8163 http:pbfluids.blogspot.com

HIV and the Kidney Joel M. Topf, MD Clinical Nephrologist St John Hospital 248.470.8163 http:pbfluids.blogspot.com

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

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 I am saying that it can happen to anybody, even me, Magic Johnson.quot;

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-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)

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.

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 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

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 0.03 0.04 0.05 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004

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

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

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

Definitive diagnosis

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

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

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

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

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%

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)

Diagnosis: echodensity does

0 I III II

Diagnosis: echodensity does

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)

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

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

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

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.

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

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.

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.

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.

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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HIV and the Kidney 2009

by Joel Topf on Jan 27, 2009

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HIV and the Kidney 2009 — Presentation Transcript