Kidney disease in HIV-positive patients 2016. 11. 16. 신장내과 R3 황규환

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

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)

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

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. 

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. 2015 Mar;11(3)

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).

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

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)

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

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):

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

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

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

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):

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

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

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.

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)

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)

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)

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

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)

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

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)

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)