1. Kidney disease in HIV-positive patients
신장내과 R3 황규환

2. AKI in HIV-positive patients
Patients with HIV are at risk for both acute kidney injury (AKI) and chronic kidney disease (CKD)
Medication nephrotoxicity
Protease inhibitors (Indinavir and atazanavir) can cause crystalluria and AKI. 
Tenofovir (nucleoside reverse transcriptase inhibitor) can cause AKI, proximal tubular dysfunction
Acyclovir, foscarnet, cidofovir, Trimethoprim-sulfamethoxazole
 HIV-associated thrombotic microangiopathy
 a rare complication of HIV infection in the ART era

3. AKI in HIV-positive patients
US military veterans, from 1986 through 2006,
17,325 HIV-positive patients, AKI occurred in 3060 (18 percent)
334 of these patients with AKI also required dialysis.
During an average follow-up of 5.7 years after hospital discharge, the HIV-positive patients who experienced AKI were significantly more likely to die (56% versus 47%)
ESRD and cardiovascular events were also significantly more common
Long-term clinical consequences of acute kidney injury in the HIV-infected.
International Society of Nephrology. 2010 Sep;78(5)

4. CKD in HIV-positive patients
HIV-associated nephropathy
The classic kidney disease of HIV infection
56%
Immune complex mediated glomerulonephritis
40% of HIV-positive patients with proteinuria and suspected HIVAN will have an alternative diagnosis on Bx.
membranous nephropathy, membranoproliferative glomerulonephritis, "lupus-like" proliferative glomerulonephritis, IgA nephropathy
Glomerulonephritis d/t HCV co-infection

5. HIV-associated nephropathy
Histologically, HIVAN is a collapsing form of focal sclerosing glomerulosclerosis (FSGS)
Pathogenesis
Infection of kidney epithelial cells by HIV
expression of HIV genes within infected kidney cells
Host factors, including genetic susceptibility
a striking racial predilection for HIV-positive blacks
Prognosis
even though among those treated with ART, many such patients will develop ESRD. 

6. Pathogenesis
a | Understanding of the mechanisms of HIV entry into renal cells remains provisional, as studies have necessarily relied on cell culture models using transformed human kidney cells and transgenic mice. In vitro, HIV enters podocytes via DC-SIGN and tubule cells via DEC205, whereas the Tat protein enters podocytes via lipid rafts and induced apoptosis of cultured podocytes. b | Expression of the HIV regulatory and accessory proteins Vpr and Nef in transgenic mice produces the glomerular and tubular features of collapsing glomerulopathy. Vpr and Tat, but not Nef, are present in human plasma. The mechanism that drives aberrant expansion of podocyte stem cells, which are located in the parietal epithelium, remains unknown. The pathology of HIVAN is characterized by podocyte loss, aberrant stem cell replenishment, tubular cell injury, and microcystic tubular dilatation. Abbreviation: HIVAN, HIV-associated nephropathy.
HIV-associated nephropathies: epidemiology, pathology, mechanisms and treatment.
Nat Rev Nephrol Mar;11(3)

7. The glomerular capillary lumina are obliterated by collapse of glomerular basement membranes, with hypertrophy and hyperplasia of overlying glomerular epithelial cells containing numerous protein resorption droplets (Jones' methenamine silver, 400x).

8. Treatment of CKD in patients with HIV
No randomized trials have specifically examined the effect of antiretroviral therapy (ART)
Most individuals will have a strong indication for ART initiation based upon criteria other than kidney dz
Supportive therapy
appropriate medication dose adjustment
enhanced monitoring for medication toxicity
avoidance of potentially nephro-toxic medications

9. Dialysis in HIV patients
There is no strong evidence to suggest that one dialysis modality is superior
Both hemodialysis and peritoneal dialysis should be considered in HIV-positive individuals approaching end-stage renal disease (ESRD)

10. Dialysis in HIV patients
Arteriovenous access outcomes in haemodialysis patients with HIV infection
Nephrol Dial Transplant (2007) 22: 465–470
Dana Mitchell, Zipporah Krishnasami, Carlton J. Young and Michael Allon
Division of Nephrology and Division of Transplant Surgery, University of Alabama at Birmingham, USA

11. Method
all patients with HIV infection receiving HD at UAB (University of Alabama at Birmingham)
during the 6.5-year period (1 January 1999 ~ 30 June 2005)
a retrospective case-control design
HIV-positive HD patients were compared with those observed in a matched group of HIV-negative patients.
underwent pre-op vascular mapping
Fistulas were placed preferentially to grafts
Arteriovenous access outcomes in haemodialysis patients with HIV infection.
Nephrol. Dial. Transplant. (2007)22 (2):

12. Method
Arteriovenous access outcomes in haemodialysis patients with HIV infection.
Nephrol. Dial. Transplant. (2007)22 (2):

13. Method
Arteriovenous access outcomes in haemodialysis patients with HIV infection.
Nephrol. Dial. Transplant. (2007)22 (2):

14. Result
Arteriovenous access outcomes in haemodialysis patients with HIV infection.
Nephrol. Dial. Transplant. (2007)22 (2):

15. Result HD access infections
Retrospective series have demonstrated a significant increase in AV graft infections and thrombosis in HIV-positive patients
a finding not observed with AV fistulae
early AVF insertion is recommended in all HIV-positive patients who are approaching ESRD and plan to use hemodialysis
Arteriovenous access outcomes in haemodialysis patients with HIV infection.
Nephrol. Dial. Transplant. (2007)22 (2):

16. Dialysis in HIV patients
The incidence of peritonitis in HIV-positive patients on chronic peritoneal dialysis has varied in different studies
In several reports, a higher incidence of Pseudomonas and fungal peritonitis was reported in HIV-positive peritoneal dialysis patients than in seronegative patients
Other studies have reported peritonitis rates comparable with that of the general ESRD population

17. Kidney transplantation in HIV-infected
More patients who would have died before the availability of ART are now receiving ART
The outcome of kidney transplantation in HIV–positive patients has been reported to be similar to the outcome in HIV-negative recipients

18. Kidney transplantation in HIV-infected
Outcomes of Kidney Transplantation in HIV-Infected Recipients
N Engl J Med. 2010 Nov 18;363(21)
Peter G. Stock, Burc Barin, Barbara Murphy, et al.

19. Method prospective, nonrandomized trial
150 HIV-infected kidney-transplant recipients were followed for up to 3 years at 19 U.S. transplantation centers.
CD4+ T-cell counts of at least 200 cells per cubic millimeter and undetectable plasma HIV-1 RNA levels
receiving stable HAART in the 16 weeks before transplantation
from both deceased and living donors
enrolled 150 patients in the study from November 2003 through June 2009
Outcomes of Kidney Transplantation in HIV-Infected Recipients.
N Engl J Med. 2010 Nov 18;363(21)

20. Method
Initial immunosuppressive therapy included glucocorticoids, cyclosporine or tacrolimus, and mycophenolate mofetil.
Sirolimus was used in patients with calcineurin-inhibitor–associated nephrotoxicity.
Antibody induction therapy with an interleukin-2–receptor blocker, anti-thymocyte globulin, or both was permitted.
Outcomes of Kidney Transplantation in HIV-Infected Recipients.
N Engl J Med. 2010 Nov 18;363(21)

21. Method Primary outcomes. Secondary outcomes
Patient survival and graft survival
Secondary outcomes
opportunistic complications, changes in the CD4+ T-cell count, and detectable plasma HIV-1 RNA levels
Survival estimates were compared with the U.S. Scientific Registry of Transplant Recipients (SRTR) results.
Outcomes of Kidney Transplantation in HIV-Infected Recipients.
N Engl J Med. 2010 Nov 18;363(21)

22. Result Outcomes of Kidney Transplantation in HIV-Infected Recipients.
N Engl J Med. 2010 Nov 18;363(21)

23. Result
The cumulative incidence of rejection was 31% at 1 year and 41% at 3 years.
The 1-year SRTR rejection rate was 12.3%
Outcomes of Kidney Transplantation in HIV-Infected Recipients.
N Engl J Med. 2010 Nov 18;363(21)

24. Result Outcomes of Kidney Transplantation in HIV-Infected Recipients.
N Engl J Med. 2010 Nov 18;363(21)

25. Result
Of the 150 kidney recipients, 57 (38%) infections that required hospitalization.
Of these infections, 69% were bacterial, 9% fungal, 6% viral, and 1% protozoal.
The most common organisms isolated were Escherichia coli (in 21 patients), enterococcus (in 17), Staphylococcus aureus (in 12), S. epidermidis (in 11), and klebsiella (in 8)
Outcomes of Kidney Transplantation in HIV-Infected Recipients.
N Engl J Med. 2010 Nov 18;363(21)

26. Conclusion
In this cohort of carefully selected HIV-infected patients, both patient- and graft survival rates were high at 1 and 3 years, with no increases in complications associated with HIV infection.
The unexpectedly high rejection rates are of serious concern, and improved strategies for minimizing rejection are needed
Outcomes of Kidney Transplantation in HIV-Infected Recipients.
N Engl J Med. 2010 Nov 18;363(21)