Managing Cardiovascular Risk in HIV

1
Managing Cardiovascular Risk in HIV

• A Toolkit for HIV Clinicians

Management of Lipids
Management of Diabetes
Smoking Cessation Counselling
CVD Risk and Assessment
Management of KidneyDisease
Management of Hypertension
2
Disclosure of Potential for Conflict of Interest
Marek Smieja, MD PhD FRCPC Cardiovascular Risk in
HIV A Toolkit for HIV Clinicians
program FINANCIAL DISCLOSURE Speakers
Bureau/Honoraria (100 donated) Abbott,
Astra-Zeneca, BI, BMS, GSK/Viiv, Merck, Pfizer,
Roche, Tibotec Grants Pfizer (Champix), Gilead
(Canadian HIV Vascular Study)
3

• There needs to be recognition among both HIV
  clinicians and cardiologists that first, these
  patients are at risk for cardiovascular disease
  and, second, we need to recognize that risk and
  figure out what we need to do to treat it."

Grinspoon SK, et al. Circulation
2008118198-210.
4
Objectives

• This CME course is designed to provide the HIV
  clinician with
• the tools needed for recognition of the various
  factors that lead to increased cardiovascular
  (CV) risk in HIV
• the knowledge required for the diagnosis of the
  factors that lead to increased CV risk in HIV
• the guidelines for the management of the factors
  that lead to increased CV risk in HIV

CME continuing medical education
5
Overview
CVD Risk and Assessment
Smoking Cessation Counselling
Management of Lipids
Management of Diabetes
Management of Hypertension
Management of Kidney Disease
6
Program Development Committee
Co-chairs Anita Rachlis Marek
Smieja Committee Linda Robinson Jean-Guy
Baril Greg Bondy Julian Falutz Marianne
Harris Mona Loutfy Alireza Zahirieh
7
CVD Risk and Assessment
8
CVD Risk Factors in the HIV Population
hs-CRP?
Lipids
Inactivity, Diet
Gender
Abdominal Obesity
Age
CVD Risk
Cigarette Smoking
Family History
-
-
Hyper-tension
HIV Infection
Hyper-glycemia
Insulin Resistance
ARV
Orange Modifiable Green Non-modifiable Purple
HIV-associated
Diabetes

• Metabolic syndrome
• ARV antiretroviral therapy hs-CRP
  high-sensitivity C-reactive protein
• Adapted from Carr A. Clinical Care Options HIV.
  Available at www.clinicaloptions.com/hiv

9
Canadian Evidence-BasedGuidelines on CV Risk in
HIV

• Primary Authors Marek Smieja
• Astha Ramaiya
• Greg Bondy
• CV Experts Jacques Genest
• Allan Sniderman
• Working Group Jean-Guy Baril
• Julian Falutz
• Marianne Harris
• Sean Hosein
• Mona Loutfy
• Anita Rachlis
• Linda Robinson

10
The Guideline Panel Asked the Following Questions

1. Does HIV infection contribute to CV risk?
2. Do traditional factors associated with increased
   CV risk have the same impact in HIV patients?
3. Does HAART contribute to CV risk in HIV?
4. Are traditional screening methods applicable in
   HIV?
5. Are traditional CV risk management strategies
   applicable in HIV?

HAART highly active antiretroviral therapy
11
Quality of the Evidence

• Grade I RCT or meta-analysis
• Grade II Observational data
• II-a. Prospective cohort study
• II-b Retrospective cohort or administrative
  database
• II-c Case-control
• Grade III Expert opinion, clinical
  experience, descriptive studies

Adapted from Smieja M, et al. Canadian
Evidence-Based Guidelines on Cardiovascular Risk
in HIV in development.
12
Strength of Recommendation

• Category A
• Strong evidence to support
• Category B
• Moderate evidence to support
• Grade C
• Poor evidence to support or recommend

Adapted from Smieja M, et al. Canadian
Evidence-Based Guidelines on Cardiovascular Risk
in HIV in development.
13
Summary

• Does HIV infection contribute to CV risk?
• HIV is a weak cardiac risk factor (B-II)
• Do traditional factors associated with increased
  CV risk have the same impact in HIV patients?
• HIV patients high smoking (A-II), other factors
  (B-ll)
• Does HAART contribute to CV risk in HIV?
• HAART PI (B-II) gt NRTI (C-II) gt NNRTI
• Starting stopping HAART (B-II)
• Are traditional screening methods applicable in
  HIV?
• Screening Framingham (B-II) time on HAART
  (C-II)
• Are traditional CV risk management strategies
  applicable in HIV?
• Treatment statins (A-I) switching ARVs (B-I)
  smoking cessation medications (A-I)

HAART highly active antiretroviral therapy
ARVs antiretrovirals PI protease inhibitor
NRTI nucleoside reverse transcriptase
inhibitor NNRTI non-nucleoside reverse
transcriptase inhibitor

• Adapted from Smieja M, et al. Canadian
  Evidence-Based Guidelines on Cardiovascular Risk
  in HIV in development.

14
Screening for all patients
Assessment How often?
History Personal or family history of CVD, hypertension, diabetes Personal habits smoking, exercise, EtOH Family history at baseline, then update Personal history, baseline, before ART, then annually
Physical Weight, BMI, waist circumference, BP Baseline, before ART, then annually
Laboratory Fasting TC, HDL-C, LDL-C, TG, (apoB) Fasting glucose, creatinine Consider hs-CRP Baseline, before ART, 3-6 months after starting ART, then annually
Calculations Framingham CV risk assessment Consider Reynolds Risk Score (if moderate risk) Creatinine clearance, (eGFR) Before ART and annually on ART Baseline, annually in men gt 45 yrs, women gt 55 yrs
ART antiretroviral therapy EtOH ethyl alcohol
BMI body mass index BP blood pressure TC
total cholesterol HDL-C high-density
lipoproteincholesterol LDL-C low-density
lipoprotein cholesterol TG triglycerides eGFR
estimated glomerular filtration rate More
frequent monitoring if patient is in the process
of lifestyle modification and/or starting or
adjusting new medications for hypertension,
hyperglycemia, or hyperlipidemia.
Adapted from Smieja M, et al. Canadian
Evidence-Based Guidelines on Cardiovascular Risk
in HIV in development.
15
Framingham Risk Score Used to Estimate 10-Year CV
Risk

• Developed for use in general population
• Thought to be reasonable predictor in
  HIV-infected population
• However, does not include HIV-specific factors
• Immune status
• Increased inflammatory markers
• Insulin resistance
• Time on HAART

Calgary Health Region online risk calculator.
Available at http//www.calgaryhealthregion.ca/h
ealthinfo/tools/heart_health.htm
16
Treatment of Increased CV Risk

• Smoking cessation counselling and medications
• Manage lipids
• Lifestyle modifications exercise, diet
• Pharmaceutical management to meet lipid targets
  based on risk stratification
• Treat hypertension and diabetes as per current
  guidelines
• Treat underlying CV disease
• Prevent CV disease in high-risk populations
• Maintain healthy renal function

Adapted from Smieja M, et al. Canadian
Evidence-Based Guidelines on Cardiovascular Risk
in HIV in development.
17
Useful Links and Resources

• On-line risk calculator (Canadian)
• http//www.calgaryhealthregion.ca/healthinfo/tools
  /heart_health.htm
• Infectious Diseases Society of America (IDSA)
  Guidelines for Managing CV Risk in HIV
• http//www.idsociety.org/Content.aspx?id5912
• European AIDS Clinical Society (EACS) Guidelines
• http//www.europeanaidsclinicalsociety.org/guideli
  nes.asp

18
Overview
CVD Risk and Assessment
Smoking Cessation Counselling
Management of Lipids
Management of Diabetes
Management of Hypertension
Management of Kidney Disease
19
Smoking Cessation Counselling
20
Tobacco Dependence is a Medical Condition
Smoking prevalence General population
20 HIV population 40-70
Heishman SJ. Nicotine Tob Res 19991(Suppl
2)S143-7.
21
The 5As Model
ASK Patients about smoking status at every visit
ADVISE Patients about the health risks of tobacco use and to quit
ASSESS Patients readiness to quit
ASSIST Patients that are ready to quit
ARRANGE Follow-up
Further information on this model available at
http//ctica.org
22
ASK(at every visit)
Hughes JR, et al. Cochrane Database Syst Rev
20052CD001007 Jorenby DE, et al. JAMA
200629656-63 Lancaster T, Stead LF. Cochrane
Database Syst Rev 20052CD001292 Lancaster T,
Stead LF. Cochrane Database Syst Rev
20053CD001118 Silagy C, et al. Cochrane
Database Syst Rev 20043CD000146 Stead LF, et
al. Cochrane Database Syst Rev 20053CD002850.
23
ADVISE

• Offer advice on quitting using messages that are
• CLEAR
• I think it is important for you to quit smoking
  now, and I can help you.
• STRONG
• As your clinician, I need you to know that
  quitting smoking is very important to protecting
  your health now and in the future.
• PERSONALIZED
• Link tobacco use to health/illness (reason for
  office visit), social/economic costs, motivation
  level and impact on others (e.g., children)

Fiore MC, et al. US Department of Health and
Human Services. Public Health Service 2008.
Available at www.surgeongeneral.gov/tobacco/defau
lt.htm
24
ASSESS..
A patients readiness to quit can be anywhere
from no way to Im ready and anywhere in
between
Stages of Behaviour Change
Pre-contemplation-Contemplation-Preparation-Action
-Maintenance
Knowledge Skills Changes in Attitude
Enablers Reward System Reinforcements
The healthcare provider focuses their efforts and
education to best motivate the patient to move
across this continuum to the right
Prochaska JO, DiClemente CC. In Norcross JC,
Goldfried MR (eds). Handbook of psychotherapy
integration 2nd ed. Oxford University Press
2005.
25
ASSIST
Three strategies have been proven to help
patients quit smoking

1. Set a QUIT DATE
2. Behavioural therapies to help patients recognize
   and adapt to TRIGGERS
3. MEDICATIONS

Hughes JR. CA Cancer J Clin 200050143-51.
26
Most Common Medications
Medication Nicotine gum Nicotine patch Nicotine inhaler Bupropion Varenicline
Treatment length 1-3 months 8-12 weeks 12-24 weeks 7-12 weeks 12 weeks
Main side effects Upset stomach Hiccups Headache Disturbed sleep Site rash Irritation of throat and nasal passages Sneezing Coughing Insomnia Nausea Depression
Dosage 2 mg, 4 mg 7 mg, 14 mg, 21 mg 6-12 cartridges per day 150 to 300 mg/day 0.5 mg qd to 1 mg bid
Nelfinavir- and ritonavir-containing regimens may inhibit CYP2B6 metabolism of bupropion and increase risk of toxicity. Monitor closely. Nelfinavir- and ritonavir-containing regimens may inhibit CYP2B6 metabolism of bupropion and increase risk of toxicity. Monitor closely. Nelfinavir- and ritonavir-containing regimens may inhibit CYP2B6 metabolism of bupropion and increase risk of toxicity. Monitor closely. Nelfinavir- and ritonavir-containing regimens may inhibit CYP2B6 metabolism of bupropion and increase risk of toxicity. Monitor closely. Nelfinavir- and ritonavir-containing regimens may inhibit CYP2B6 metabolism of bupropion and increase risk of toxicity. Monitor closely. Nelfinavir- and ritonavir-containing regimens may inhibit CYP2B6 metabolism of bupropion and increase risk of toxicity. Monitor closely.
Hughes JR, et al. Cochrane Database Syst Rev
20044CD000031 Jorenby DE, et al. JAMA
200629656-63 Silagy C, et al. Cochrane
Database Syst Rev 20043CD000146. Hesse LM, et
al. Drug Metab Dispos 200129100-102.
27
ARRANGE

• Follow-up contact should begin soon after the
  quit date, preferably during the first week.
• A second follow-up contact is recommended within
  the first month.
• Schedule further follow-up contacts as indicated.

• For patients who are abstinent, congratulate them
  on their success.
• Assess problems and anticipate challenges in the
  immediate future.
• Assess medication use and problems.
• Remind patients of quit support mechanisms.
• Address tobacco use at next clinical visit (treat
  tobacco use as a chronic disease).
• If tobacco use has occurred, review circumstances
  and elicit recommitment to total abstinence.
  

US Department of Health and Human Services.
Available at www.surgeongeneral.gov/tobacco/defau
lt.htm (accessed Aug. 17, 2009)
28
Useful Links and Resources
Flow Sheet for Chart www.ctica.org/cessation/cessa
tion.html downloads Smokers Helpline
1-877-513-5333www.smokershelpline.ca Guidelines
from the US Department of Health and Human
Services, Office of the Surgeon General Ministry
of Health Promotion www.mhp.gov.on.ca/english/heal
th/smoke_free/default.asp Physicians for a
Smoke-Free Canada www.smoke-free.ca
29
Management of Lipids
30
Screen fasting lipid profile in

• Men 40 years, women 50 years or
  postmenopausal
• All adults with any of the following, regardless
  of age
• Diabetes
• Cigarette smoking
• Hypertension
• Obesity (BMI gt 27 kg/m2)
• Family history of premature CAD
• Clinical signs of hyperlipidemia
• Evidence of atherosclerosis
• Rheumatoid arthritis, systemic lupus
  erythematosis, psoriasis
• HIV infection on HAART
• eGFR lt 60 mL/min/1.73 m2
• Erectile dysfunction
• Screen children with a family history of
  hypercholesterolemia or chylomicronemia

BMI body mass index CAD coronary artery
disease eGFR estimated glomerular filtration
rate HAART highly-active antiretroviral therapy
Genest J. et al. Can J. Cardiol 200925567-79.
31
First Steps to Managing Lipids
TREAT TO TARGET
Adapted from Genest J, et al. Can J Cardiol
200925567-79.
32

• Lifestyle Interventions
• Dietician consultation (reduced saturated
  fats/sugars)
• Smoking cessation consultation
• Weight reduction and maintenance
• Exercise (daily) at least 30 min/day

33
When to Treat
Risk Level Initiate treatment if
High CAD, PVD, atherosclerosis Most patients with diabetes Framingham 20 Reynolds Risk Sc. 20 Consider treatment in all patients
Moderate Framingham 10-19 LDL-C gt 3.5 mmol/L TCHDL-C gt 5.0 hs-CRP gt 2 mg/L (in men gt 50 yrs, women gt 60 yrs) Family history and hs-CRP modulates risk score (RRS)
Low Framingham lt 10 LDL-C 5.0 mmol/L
Double the risk if a first generation relative
has suffered a CV event prior to the age of 60
Genest J, et al. Can J Cardiol 200925567-79.
34
Target Lipid Levels
Primary targets Primary targets
Risk Level LDL-C (mmol/L) Alternate Apo-B (g/L)
High CAD, PVD, atherosclerosis Most patients with diabetes Framingham 20 RRS 20 lt 2.0 or 50 ? LDL-C lt 0.80
Moderate Framingham 10-19 lt 2.0 or 50 ? LDL-C lt 0.80
Low Framingham lt 10 50 ? LDL-C
Secondary (optional targets) once LDL-C at goal
TCHDL-C lt 4.0 Non-HDL-C lt 3.5 mmol/L TG lt
1.7 mmol/L Apo-BApo-AI lt 0.80 hs-CRP lt 2 mg/L
CAD coronary artery disease PVD peripheral
vascular disease RRS Reynolds Risk Score
Adapted from Genest J, et al. Can J Cardiol
200925567-79.
35
Lipid-Lowering Agents and PIs Drug Interactions
Area under the curve (AUC) ??? with darunavir.
Adapted from Fichtenbaum CJ, et al. AIDS
200216569-577 Hsyu PH, et al. Antimicrob
Agents Chemother 2001453445-50 Gerber JG, et
al. IAS 2003. Abstract 870 Carr RA, et al. ICAAC
2000. Abstract 1644 Telzir Package Insert 2003
Gerber JG, et al. CROI 2004. Abstract 603
Reyataz Package Insert 2005 Aptivus Product
Label 2005.
36
Summary Switching ARVs

• Switching ARVs is an appropriate strategy to
  manage dyslipidemia for some patients
• Maintaining virologic control is of paramount
  importance
• Must consider treatment history, resistance
  mutations present
• Potency of new regimen must be adequate

37
Useful Links and Resources

• On-line risk calculator (Canadian)
• http//www.calgaryhealthregion.ca/healthinfo/tools
  /heart_health.htm
• Infectious Diseases Society of America (IDSA)
  Guidelines for Managing CV Risk in HIV
• http//www.idsociety.org/Content.aspx?id5912
• European AIDS Clinical Society (EACS) Guidelines
• http//www.europeanaidsclinicalsociety.org/guideli
  nes.asp
• Toronto General Hospital HIV Clinic Drug
  Interaction Tables
• http//www.hivclinic.ca/main/drugs_interact.html
  (see Lipid-lowering drugs)

38
Management of Diabetes
39
Diabetes Risk Factors

• HIV-associated DM
• Risk Factors
• Peripheral lipoatrophy
• Reduced adiponectin
• Increased liver/muscle fat
• Inflammatory cytokines
• Low testosterone
• HCV co-infection
• Protease inhibitors, d4T

• Classical DM
• Risk Factors
• Abdominal obesity
• Physical inactivity
• Genetic
• Family history
• Race/ethnicity
• Older age
• Dyslipidemia

InsulinResistance
DM diabetes mellitus HCV hepatitis C virus
d4T stavudine
Adapted from Dube MP. Clinical Care Options.
Available at www.clinicaloptions.com/HIV/Managem
ent Series/Insulin Resistance/Modules/Dube.aspx
40
Diagnosis of Diabetes
FPG 7.0 mmol/L
6.1-6.9 mmol/L
Confirmedby any of these 3 laboratory tests
on another day
OR
Casual PG gt 11.1 mmol/L with symptoms of
polydipsia or polyuria or unexplained weight loss
AND/OR
OR
2h PG in a 75-g OGTT gt 11.1 mmol/L
7.8-11.1 mmol/L
IFG and/orIGT
DIABETES

• FPG fasting plasma glucose PG plasma glucose
  OGTT oral glucose tolerance test IFG impaired
  fasting glucose IGT impaired glucose tolerance
• Adapted from Canadian Diabetes Association. Can J
  Diabetes 200832(Suppl 1)S1-S201.

41
Management of Diabetes
DIABETES
Adapted from Canadian Diabetes Association. Can J
Diabetes 200832(Suppl 1)S1-S201.
42
Targets For Treatment
No evidence that targets for the HIV-infected population should differ from those for the HIV-uninfected population No evidence that targets for the HIV-infected population should differ from those for the HIV-uninfected population
Parameter Goal
Glycemic control
A1C, (try to achieve target within 6-12 months) 7.0
FPG or pre-prandial PG (mmol/L) 4.0 7.0
2-hr post-prandial PG (mmol/L) 5.0 10.0
Blood pressure, mm Hg lt 130/80
Lipids
Primary target LDL-C (mmol/L) 2.0
Secondary target TC/HDL-C ratio lt 4.0
Canadian Diabetes Association. Can J Diabetes
200832(Suppl 1)S1-S201.
43
Useful Links and Resources

• Diabetes Management and Assessment Flow Sheet
• http//www.sgfp.ca/forms.html
• CDA Diabetes Guidelines 2008
• http//www.diabetes.ca/for-professionals/resources
  /2008-cpg/ download- Appendix 2 sample flow
  sheet p.S195
• Toronto General Hospital HIV Clinic
• Drug Interaction Tables
• http//www.hivclinic.ca/main/drugs_interact.html
• (see Oral hypoglycemics)

44
Management of Hypertension
45
Diagnosis of Hypertension
Elevated Out ofthe Office BPMeasurement
Elevated RandomOffice BPMeasurement
Hypertension Visit 1 BP Measurement, History and
Physical Examination
Diagnostic tests ordering at visit 1 or 2
Hypertension Visit 2 within 1 month
Adapted from the 2009 CHEP Recommendations.
Available at www.hypertension.ca/chep/recommendat
ions-2009
46
Diagnosis of Hypertension (contd)
BP 140-179 / 90-109 mm Hg

• Patients with high normal blood pressure (clinic
  SBP 130-139 and/or DBP 85-89) should be followed
  annually.
• ABPM ambulatory blood pressure monitoring
  (please see back-up slides for more information
  on ABPM).
• Adapted from the 2009 CHEP Recommendations.
  Available at www.hypertension.ca/chep/recommendat
  ions-2009

47
When to Treat
Thresholds for Initiation of Antihypertensive Agents Thresholds for Initiation of Antihypertensive Agents
Condition Initiation
SBP or DBP mm Hg
Systolic or diastolic hypertension ? 140/90
Diabetes Chronic kidney disease ? 130/80
2 consecutive measures thresholds TREAT
SBP systolic blood pressure DBP diastolic
blood pressure Adapted from the 2009 CHEP
Recommendations. Available at www.hypertension.ca
/chep/recommendations-2009
48
Goals of Therapy
Target Values for Treatment of Hypertension Target Values for Treatment of Hypertension
Condition Target
SBP and DBP mm Hg
Isolated systolic hypertension lt 140
Systolic/diastolic hypertension Systolic BP Diastolic BP lt 140 lt 90
Diabetes or chronic kidney disease Systolic Diastolic lt 130 lt 80
Adapted from the 2009 CHEP Recommendations.
Available at www.hypertension.ca/chep/recommendat
ions-2009
49
How to Treat
Not indicated as first-line therapy gt 60 years.

• ACE-I angiotensin-converting enzyme inhibitor
  ARB angiotensin II receptor blocker CCB
  calcium-channel blocker HTN hypertension
• Adapted from the 2009 CHEP Recommendations.
  Available at www.hypertension.ca/chep/recommendat
  ions-2009

50
Lifestyle Therapies
Intervention Target
Reduce foods with added sodium lt 2300 mg/day
Weight loss BMI lt 25 kg/m2
Alcohol restriction lt 2 drinks/day
Physical activity 30-60 minutes 4-7 days/week
Dietary patterns DASH diet
Smoking cessation Smoke free environment
Waist circumference Europid South Asian, Chinese Men Women lt 94 cm lt 80 cm lt 90 cm lt 80 cm
DASH Dietary Approaches to Stop Hypertension
BMI body mass index DASH diet emphasizes
fruits, vegetables and low-fat dairy products,
dietary and soluble fiber, whole grains and
protein from plant sources that is reduced in
saturated fat and cholesterol.
Adapted from the 2009 CHEP Recommendations.
Available at www.hypertension.ca/chep/recommendat
ions-2009
51
How to Treat
TARGET lt140/90 mm Hg (lt130/80 mm Hg in diabetes
or CKD)
Lifestyle modification
A combination of 2 first-line drugs may be
considered as initial therapy if BP is gt20 mm Hg
systolic or gt10 mm Hg diastolic above target
Initial therapy

• CONSIDER
• Non-adherence
• Secondary HTN
• Interfering drugs
• or lifestyle
• White coat effect

Dual combination
Not indicated as first-line therapy gt 60 years.
Triple or quadruple therapy
Adapted from the 2009 CHEP Recommendations.
Available at www.hypertension.ca/chep/recommendat
ions-2009
52
Special Cases/Drug Classes
Indication Target BP Recommended Drugs
Post MI lt 140/90 mm Hg Beta-blocker ACE-I or ARB
CKD lt 130/80 mm Hg ACE-I or ARB
Diabetes with nephropathy lt 130/80 mm Hg ACE-I or ARB
Diabetes without nephropathy lt 130/80 mm Hg ACE-I, ARB, or thiazide diuretic or DHP-CCB
Stroke/TIA lt 140/90 mm Hg ACE-I/diuretic combination

• ARV Drug Interactions http//www.hivclinic.ca/mai
  n/drugs_interact.html
• Adapted from the 2009 CHEP Recommendations.
  Available at www.hypertension.ca/chep/recommendat
  ions-2009

53
Follow-up of Hypertension
Adapted from the 2009 CHEP Recommendations.
Available at www.hypertension.ca/chep/recommendat
ions-2009
54
Useful Links and Resources
CHEP Hypertension Recommendations
2009 www.hypertension.ca/chep/recommendations-2009
Patient Guides for Home BP Monitoring and
Diet www.hypertension.qc.ca (french) http//hypert
ension.ca/chep/educational-resources/public-inform
ation/ (english) Toronto General Hospital HIV
Clinic Drug Interaction Tables www.hivclinic.ca/
main/drugs_interact.html (look up individual
cardiac medications in PI and NNRTI tables)
55
Management of Kidney Disease
56
HIV and the Kidney

• The renal tubules have clearly been demonstrated
  to be a reservoir for HIV infection
• Active viral replication in renal tubular cells
  can result in high-grade proteinuria with rapid
  decline in renal function
• Pathological diagnosis HIV-associated
  nephropathy (HIVAN)
• HIVAN seen almost exclusively in individuals of
  African descent who are not actively treated with
  ARVs

Wyatt CM, Klotman PE. Clin J Am Soc Nephrol
20072S20-24.
57
Classification of CKD
Stage Description GFR (mL/min/1.73m2)
I Abnormal ultrasound OR hematuria OR proteinuria gt 90
II mild ? GFR 60 - 89
III moderate ? GFR 30 - 59
IV severe ? GFR 15 - 29
V End-stage renal disease lt 15
Modification of Diet in Renal Disease (formula)
is recommended for staging of CKD GFR
glomerular filtration rate
National Kidney Foundation. Am J Kidney Dis
200239(2 Suppl 1)S1-266.
58
Recreational drug use
Diabetes
Proteinuria
Smoking
Family hx of kidney disease
African- American descent
Risk Factors For CKD in HIV
Dyslipidemia
Low CD4
Use of nephrotoxic medications
Hypertension
HBV/HCV co-infection
Established CVD
Family hx of CVD
Older age
Orange non-modifiable Blue modifiable
59
Medications and Renal Disease
Prerenal Tubular Injury Allergic Interstitial Nephritis Thrombotic Microangiopathy Obstructive
ACE-I Amphotericin NSAIDS Cyclosporine Diuretics Interferon Cidofovir Adefovir Tenofovir Didanosine Lamivudine Stavudine Aminoglycosides Amphotericin Cocaine Foscarnet Pentamidine Abacavir Indinavir Ritonavir Acyclovir Cephalosporins Penicillins Ciprofloxacin TMP/SMX Rifampin Indinavir Cocaine Cyclosporine Valacyclovir Indinavir Atazanavir Acyclovir Foscarnet Sulfadiazine Sulfonamides
TMP/SMX trimethoprim and sulfamethoxazole
Guo X, Nzerue C. Cleve Clin J Med 200269289-312.
60
CKD in HIV 10-Step Approach

• Confirm finding with repeat testing
• Estimate renal function in terms of GFR
• MDRD formula recommended for CKD staging
• Determine rate of change of renal function
• Quantify the degree of proteinuria
• Normal lt 150 mg/day of proteinuria lt 30 mg/day
  albuminuria
• Assess for the presence of hematuria
• Identify potential nephrotoxins
• NSAIDS, IV contrast dye, aminoglycosides,
  high-dose acyclovir, amphotericin B, cidofovir
  (and caution with adefovir)
• Rule out ECF volume depletion or urinary
  obstruction
• Identify risk factors for CKD
• Diabetes mellitus, hypertension, smoking history,
  dyslipidemia, family history of CVD, established
  CVD, low CD4 count
• Renally dose ALL medications
• Cockcroft-Gault formula recommended for drug
  dosing
• Consider a nephrology referral

61
Initial Work-up for CKD in HIV
Initial workup When to refer
Serum Cr, electrolytes, Ca, Mg, phosphate, albumin CBC, liver enzymes and liver function tests Hepatitis B C serologies Screen for diabetes mellitus, lipid profile Acute renal failure Rapidly declining renal function eGFR lt 30 mL/min
Urine Spot urine albumincreatinine ratio AND/OR 24-hr collection for CrCl and proteinuria Persistent proteinuria AlbuminCr ratio gt 60 ProteinCr ratio gt 90
Imaging Renal ultrasound Urological assessment if evidence of obstruction
with repeat testing Cr creatinine Ca calcium
Mg magnesium CBC complete blood count eGFR
estimated glomerular filtration rate CrCl
creatinine clearance
62
Management of CKD

• Control Risk Factors for CKD
• Hypertension target BP lt 130/80 mm Hg consider
  ACE-I or ARB as initial choice
• Diabetes target HbA1C lt 7
• Dyslipidemia treat stage 1-3 CKD according to
  general population guidelines treat stage 4
  CKD to LDL-C lt 2.0 mmol/L
• Established CVD antiplatelet therapy, statins,
  ACE-I or ARBs

• Delay Progression of CKD
• Treat underlying risk factor/disease
• Avoid nephrotoxins (especially NSAIDS)
• Treat proteinuria
• - ACE-1 or ARB titrate as toletated by BP and
  serum potassium
• - Dietary counselling on potassium restriction
  and/or diuretics to control serum potassium
• Target BP lt 130/80 mm Hg

Reduce CVD Risk
63
Summary

• Risk factors for CKD and CVD are similar
• Management of patients with CKD involves
• Controlling risk factors diabetes, hypertension
• Delaying progression
• Reducing CVD risk
• Avoiding nephrotoxins (consider OTC use of
  NSAIDS)
• Renally dosing all medications
• Specialist/nephrologist opinion should be
  considered for patients with rapidly falling GFR,
  GFR lt 30 mL/min, and persistent proteinuria
  despite conservative therapy

64
Useful Links and Resources

• eGFR calculator, nutritional guide, patient
  health practitioner information on CKD
• www.ukidney.com
• Canadian Guidelines for CKD
• www.cmaj.ca/cgi/content/full/179/11/1154
• IDSA Guidelines for CKD in HIV
• www.journals.uchicago.edu/doi/pdf/10.1086/430257
• ARV Dosing Adjustments for Impaired Renal
  Function
• www.aidsetc.org/aidsetc?pageet-03-00-02

65
Overview
CVD Risk and Assessment
Smoking Cessation Counselling
Management of Lipids
Management of Diabetes
Management of Hypertension
Management of Kidney Disease
66
(No Transcript)
67
(No Transcript)