Associations of CKD With Infectious Disease - Bertrand Jaber

5/21/2018 Associations of CKD With Infectious Disease - Bertrand Jaber

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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)?

Documents

Associations of CKD With Infectious Disease - Bertrand Jaber