Professional Documents
Culture Documents
HIV e rene
16.6%
16%
Cerebrovascular
14%
Diabetes
12%
Hypertension
Myocardial infarction
10%
Lipodystrophy
8%
eGFR <60
6%
3.4%
4%
2%
0%
1.6%
0.6%
0.5%
0.3%
0.3% 0.1%0
1.5%
1.4%
1.0%
0.2%0
0.8%
4.3%
3.2%
1.1%
0.6%
Dec 2014
25%
20%
15%
10%
8.5%
5%
1.3%1.6%
0.4%
0%
5.7%
5.7%
4.9%
1.5%
3.0%
2.5%
0.7%
3.3%
4.0%
2.5%
5.1%
1.8%
0.6%
0.6%
4.6%
3.4%
Cerebrovascular
Myocardial infarction
Non-AIDS defining malignancies
Diabetes
Lipodystrophy
Hypertension
eGFR <60
Dec 2014
Blood
Blood
Tubular Renal
cell
Proximal
tubule
Nucleot
ide
analogu
es
hOATP
hOATP 1-3
1-3
MRP2
MRP2
Nucleotide
Nucleotide analogues
analogues excretion
excretion
tenofov
ir,
adefovir
,
cidofovi
r
Poster # 795
Safety of Tenofovir Alafenamide in
Renal Impairment
Anton Pozniak
25%
20%
15%
10%
8.5%
5%
1.3%1.6%
0.4%
0%
5.7%
5.7%
4.9%
1.5%
3.0%
2.5%
0.7%
3.3%
4.0%
2.5%
5.1%
1.8%
0.6%
0.6%
4.6%
3.4%
Cerebrovascular
Myocardial infarction
Non-AIDS defining malignancies
Diabetes
Lipodystrophy
Hypertension
eGFR <60
Dec 2014
Virus
Drugs
Severe complications
No. of patients
with events
31
63
14
1.4
1.5
1.4
2.5
0.1
1.5
114
Relative Risk
95% CI
Favours DC
Favours VS
10
Renal epithelial cells produce and spread HIV1 via T-cell contact
Blasi M et al.
Objectives:Increasing evidence supports the role of the kidney as a reservoir for HIV-1. Invitro co-cultivation of HIV-infected T cells with renal tubule epithelial (RTE) cells results in
virus transfer to the latter, whereas cell-free virus infection is inefficient. We further
characterized the fate of HIV-1 after it is internalized in renal epithelial cells.
Methods:Primary or immortalized CD4+ cells were infected with a green fluorescent protein
(GFP)-expressing replication competent HIV-1. HIV-1 transfer from T cells to RTE cells was
carried out in a co-culture system and evaluated by fluorescence-activated cell sorting
analysis. HIV-1 integration in renal cells was evaluated by Alu-PCR and the production of
infectious particles was assessed by p24-ELISA and TZM-bl assay. HIV-infected renal cells
were used as donor cells in a co-culture system to evaluate their ability to transfer the virus
back to T cells.
Results:Renal cells become productively infected by HIV-1 and multiple copies of HIV-1 can be
transferred from infected T cells to renal cells. Two separate cell populations were identified
among infected renal cells based on reporter gene GFP expression level (low vs. high), only
the high showing sensitivity to azidothymidine and ritonavir. Co-cultivation of HIV-1-infected
renal cells with noninfected T cells resulted in HIV-1 transmission to T cells, supporting
bidirectional exchange of virus between T cells and kidney-derived cells. Persistent
expression and generation of infectious virus in renal cells required HIV integration.
#793
Spectrum of HIV-Associated Kidney Disease in the Era of Combination
Antiretroviral Therapy
John Booth
We reviewed consecutive renal biopsies (1998-2012) of HIV+ patients
attending eight clinics in the UK.
This is the first study to demonstrate a relationship between HIV
replication and ICKD (immune complex kidney disease) .
Compared to HIVAN, ICKD was associated with less advanced
immunodeficiency and a lower rate of progression to ESKD.
The observed association with HIV viraemia for both core ICKD and
HIVAN may imply a pathogenetic role of HIV replication and its associated
immune activation;
it also suggests that suppressive ART may reduce the risk of developing
these types of kidney disease
HCV
I pazienti co-infetti hanno una prognosi renale peggiore.
La presenza di crioglobuline un fattore prognostico di
aumentata mortalit
Fabrizi, F. et al. Hepatitis C virus increases
the risk of kidney disease among HIV-positive
patients: Systematic review and metaanalysis. J Med Virol. 2015. [Epub ahead of
print]
I nuovi farmaci:
Cobicistat
Dolutegravir
(e rilpivirina)
Proximal Tubule
Cell
m
Frroom
redd F
e
Fiilltteer erruulluuss
C
Crr F lom
e
G
Glom
Blood Vessel
Urinary Space
Forillustrative
illustrative
purposes
only.only.
For
purposes
only.
For illustrative
purposes
Lepist EI, et al. ICAAC 2011. Abstract A1-1724; 2 German P, et al. J Acquir Immune Defic Syndr. 2012;61:32-40; 3 Lepist EI, Ray AS. Expert Opin
Drug Metab Toxicol. 2012;8:433-448; 4 Cohen C, et al. CROI 2010. San Francisco, CA. 58LB; 5 Andreev E, et al. J Intern Med. 1999;246:247-252; 6
Naderer O, et al. Antimicrob Agents Chemother. 1997;41:2466-2470.
1
Anni
120
100
eGFR
80
60
40
>25%
20
0
In ultimo, 3 FAQ:
1) Che fare nella pratica clinica
quotidiana?
eGFR = 141 * min(SCr/k, 1) * max(SCr/k, 1)-1,209 * 0,993Et * 1,018 (F) * 1,159 (B)
k = 0,7 (F), 0,9 (M)
-0,411 (M)
-0,329 (F),
Cistatina C
Pros
Polipeptide di 13 kD
prodotto da tutte le cellule
nucleate
Conc. Plasmatica
indipendente da massa
muscolare, sesso e razza
Filtrata dal glomerulo in
assenza di quota di
secrezione tubulare
Non interferenze nei
metodi analitici
Cons
Cistatina C e infezione da
HIV
HIV+
(261)
Controlli
(193)
eGFR (MDRD)
104
93
< 0.001
Cocroft-Gault
118
106
< 0.001
99
120
< 0.001
eGFR (Cys)
0.33
< 0.01
- 0.29
< 0.01
Accuratezza di eGFRcys e
CD4
Accuratezza 30%
MDRD
75%
CKD-EPI
82%
CDK-EPICys 80%
CKD-EPImix 81%
Gagneux-Brunon A et al;
AIDS 2013; 27
proteine a basso pm
fosforo
glucosio
acido urico
Proteinuria tubulare
Gradi di Proteinuria
Microalbuminuria ACR > 30 < 200
mg/g
Proteinuria franca ACR > 200 mg/g
PCR > 0,2 g/g
Proteinuria lieve:
PCR 0,2 1,0 g/g
Proteinuria moderata: PCR 1,0 3,0
g/g
Proteinuria grave: PCR > 3,0 g/g
Glomerulosclerosi
Tubulo Glomerulo
Sovraccarico tubulare
Grazie per
lattenzione