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Associations of Chronic Kidney
Disease with Infectious Disease
Bertrand L. Jaber, M.D.
Tufts University School of Medicine, Boston, MA
KDIGO Controversies Conference, Amsterdam, The Netherlands
October 12-14, 2006
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Objectives
What is known?
Review the evidence
What can be done with what is known?Provide clinical practice recommendations
What needs to be known?
Provide clinical research recommendations
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Review of the Evidence
Main Topics
CKD and 5 chronicinfectious diseases (CID) ofglobal importance
Vaccination strategies inCKD
Potential pitfalls of GFRestimates in infectious
disease
Other Topics
CKD and acute infectiousdiseases
Pneumonia
Sepsis
CKD-T (transplant) and
infectious disease
CKD and infectious disease
in children
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The CKD-CID Complex
CKD CID
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The CKD-CID Complex
CKD CID
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Original CKD Conceptual Framework
Susceptibility
factor
Initiation
factor
Progression
factor
End-stage
factor
HIV, HCV, HBV
CID CKD
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Conceptual Framework: CKD in the
Natural Course of CID
Exposure Incubation RecoveryDisease
manifestation
Death
Remission ChronicstateReactivation
CKD can be present at any stage
during the course of CID
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Is CKD a Risk Multiplier for CID?
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Stage-5 CKD-D and Infectious
Disease: What Have We Learned?
The Analogy with CVD!
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Infection 2nd Leading Cause of Death
(15%) in Dialysis Patients Following CVD
23.0
2.80.3 1.1
0
5
10
15
20
25
Septicemia Pulmonary
Infections
Viral
Infections
Other
Infection-relateddeathr
ate
(per1000patientyears)
Total Death Rate = 176 deaths er 1000 atient ears USRDS 2003 Annual R
Acute
infections
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Sepsis-Related Mortality of Dialysis Patients
Compared with the General Population
0.0001
0.001
0.010.1
1
10
100
25-34 35-44 45-54 55-64 65-74 75-84 >85
Age (years)
An
nualMortality(%
)
Sarnak & Jaber: Kidney Int 58:17581764,
100-fold
Dialysis Population
General Population
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Pulmonary Infectious Mortality of Dialysis
Patients Compared with the General Populatio
Sarnak & Jaber: Chest 120:1883-1887, 2
0.00.2
0.4
0.6
0.8
1.01.2
25-34 35-44 45-54 55-64 65-74 75-84
Age (years)
An
nualMor
tality(%)
Dialysis Population
General Population
10-fold
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Susceptibility of Patients with
CKD to Infections
Virulence of
microorganismsDialysis-related Fact
(for CKD-5-D)
Impaired Host Immunity
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Pathogenesis of Infections in CKD
Virulence of
microorganisms
Impaired Host Immunity
Dialysis-related Facto
(for CKD-5-D)
- Neutrophil dysfunction
- Monocyte dysfunction
- Impaired T-cell activation
- Impaired humoral responses
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What
AboutC
KDasaRi
sk
Multiplieri
nPatien
tswith
CID?
1. Prevalence of CKD in CID
2. Association of CKD with CID-associatedadverse outcomes
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Infections of Global Importance
15 40
170
300
350
0
100
200
300
400
TB HIV HCV Malaria HBV
Estima
tednumber(million
www.wh
Overallburden of
874 million
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Proposed Framework: CKD as a
Risk/Prognostic Factor for Infectious Diseas
Infectious
disease (ID)
CKD prevalence CKD as a risk
factor for ID
morbidity
CKD as a ris
factor for ID
mortality
HIV
HCV
HBV
Malaria
TB
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HIV and CKD
http://www.herpes-coldsores.com/std -
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HAART and Incidence of HIVAN: A
12-Year Cohort Study
26
14
7
0
10
20
30
No
antiretroviral
therapy
Nucleoside
analogue
therapy
Highly-active
antiretroviral
therapy
H
IVANincidence
(per
1000pe
rson-yea
rs)
Lucas GM et al: AIDS 18:541-6, 2
CDC N ti l S ill f Di l i
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CDC National Surveillance of Dialysis-
Associated Diseases, 1995-2002 U.S.
- HIV/AIDS -
1.4 1.4 1.5 1.5
0.7
0.5 0.4 0.4
0
0.5
1
1.5
2
1995 1999 2001 2002
Percent
ofpatients(%)
HIV infectionAIDS
Finelli L et al: Seminars in Dialysis18:52-61, 200
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Proteinuria/Increased Serum Creatinine in
HIV-Infected Patients
Markers of HIV-related kidney disease:- HIVAN
- Other HIV-related glomerular diseases- Nephrotoxicity of HIV-related drugs
Indicators of poor health status as a result of:
Hypertension
Diabetes mellitus
Cardiovascular disease
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Summary of HIV-CKD StudiesAuthor Study design Sample size Renal predictor
variable
Outcome
variable
Results (multivariate
analyses)
Lewden C
(2002)Multicenter
prospective
cohort study(France)
1155 HIV-
infected
adults
Baseline and
post-treatment
(4-month) sCr 4.0
Serum creatinine (mg/dl)
ProtectiveHBSAb
response(%)
Fraser GM et al: J Hepatol 21:450-4, 1994
75%
84%
95%
0
20
40
60
80
100
= 60
Age (years)
Protec
tiveHBSAb
response(%)
Averhoff F et al: Am J Prev Med 15:1-8, 1998
CDC: MMWR 50 No. RR-5 2001
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Antibody Response to Engerix-B and Recombivax-HB
Vaccination in Stage-5 CKD-D (N = 14,456)
40%
58%
0
20
40
60
80
100
Engerix-B (4
doses)
Recombivax HB
(3 doses)
Cumulat
iveresponse
rateat1-year(%)
P < 0.000177%
53%
0
20
40
60
80
100
Engerix-B (4
doses)
Recombivax HB
(3 doses)
Persistentprotective
HBsAb
after1year
Lacson E et al: Hemod
9:367-75Odds ratio for antibody response to Engerix (vs. Recombivax) = 1.96 (95% CI 1.56,
2.45) adjusted for age, gender, race, diabetes, vintage, BSA, hemoglobin, and eKt/V
P < 0.0001
Pneumococcal Vaccine: Antibody
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Pneumococcal Vaccine: Antibody
Response in Dialysis Patients
0
200
400
600
800
1000
After 1st Dose 2 Years Repeat Dose
Pneumovax Administration
AntibodyTiter(ng/m
l)
Linnemann CC et al:Arch Int Med 146:1554-6,
** P < 0.01 vs. 2 years
Influenza Vaccination Rates in CKD 5 D
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Influenza Vaccination Rates in CKD-5-D
are Below U.S. National Objectives90%
60%
30%
60%
39%
49%
0%
20%
40%
60%
80%
100%
HD PD Whites Non
Whites
2000
Objective
2010
Objective___________________ __________________________________________
Dialysis Patients General PopulationMMWR 50:532-37,
Gilbertson DT et al: Kidne Int 63:738-743
Odds of Hospitalization and Death are
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Odds of Hospitalization and Death are
Lower among Vaccinated Dialysis Patients
0.950.88
0.75
0.84
0.75
0.6
0.7
0.8
0.9
11.1
1.2
Any
Cause
Influenza Any
Cause
Cardiac Infection
_______________ _________________________
Hospitalization Death
Gilbertson DT et al: Kidney Int 63:738-743,
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What About Other Vaccines?
Other vaccines such as diphteria, tetanus,polio (DTP) and are not well studied in CKD
The usual schedule is recommended if
indicated
Protection is likely to be suboptimal as with
other vaccines
Kausz AT & Gilbertson DT: Advances in Chronic Kidney Disease 13:209-214,
Dinits-Pensy M et al: Am J Kidney Dise 46:997-1011,
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Workgroup Tasks: Clinical and
Research Recommendations
Should we screen for CKD in chronic infectious diseases(HBV, HCV, and HIV)?
Should we vaccinate in earlier stages of CKD (e.g. stage 4)
Do we need better tools to estimate kidney functionin chronic infectious diseases (HBV, HCV, and HIV)?