Chronic Kidney Disease:Chronic Kidney Disease:Collaborative Care Through The Stages.Collaborative Care Through The Stages.
Family Medicine Grand RoundsFamily Medicine Grand Rounds
University of VirginiaUniversity of VirginiaJanuary 23, 2009January 23, 2009
Rasheed A Balogun, MD FACP FASNDivision of Nephrology, University of Virginia
Charlottesville, VA
Chronic Kidney Disease:Chronic Kidney Disease:Collaborative Care Through The Stages.Collaborative Care Through The Stages.
(Part 2) (Part 2)Family Medicine Grand RoundsFamily Medicine Grand Rounds
University of VirginiaUniversity of VirginiaMarch 13, 2009March 13, 2009
Rasheed A Balogun, MD FACP FASNDivision of Nephrology, University of Virginia
Charlottesville, VA
Jan 23 2009 12:30 PM Collaborative Care of CKD 49
Disclosure Statements Current ACCME guidelines state that participants in CME activities
should be made aware of any affiliation or financial interest that may affect the faculty member’s contributions. Each faculty member has completed a statement of disclosure, which includes funding sources other than the honorarium received for this program. The faculty have provided the following information on sources of funding that may be perceived as a potential conflict of interest.
Rasheed Balogun: research funding from National Kidney Foundation-Vas: received honoraria from Abbott Laboratories and Genzyme Therapeutics: board member (chair MAB), NKF-Va: will not discuss any non-FDA approved products
Jan 23 2009 12:30 PM Collaborative Care of CKD 50
Outline/Objectives Define CKD
Review national and local epidemiology + outcome data
Review CKD: Clinical Action Plan Detect CKD Prevent progression of CKD Diagnosis and treat CVD Treat co-morbid conditions and complications Refer to nephrology: Emphasize role of the non-
nephrologist MD in CKD care
Jan 23 2009 12:30 PM Collaborative Care of CKD 51
Cardiologist
PCP
Dietician
NephrologistPatient
Nurses and other health care professionals
Teamwork in CKD Care
Jan 23 2009 12:30 PM Collaborative Care of CKD 52Chronic Kidney Disease in USA Zabetakis. Am J Kidney Dis. 2000;36(suppl 3):S31.
Associated Systemic Complications in Chronic Kidney Disease (CKD)
Anemia of CKD
Hypertension
Cardiovascular disease
Dyslipidemia
Osteodystrophy
Metabolic acidosis
Malnutrition
Diabetes mellitus
Jan 23 2009 12:30 PM Collaborative Care of CKD 53
Work-up of Anemia of CKD: When?
Normal 12 – 14 Hb g/dL (Hct 36-42)
Anemia Men, Postmenopausal women
≤12 Hb g/dL (Hct < 36)
premenopausal women
≤11.0 Hb g/dL
NKF. Am J Kidney Dis. 2001;37:S182.
Guideline 1
Jan 23 2009 12:30 PM Collaborative Care of CKD 54
Adapted from: Fauci.Harrison’s Principles of Internal Medicine. 1998:334.
Red blood cellsRed blood cells O2 deliveryO2 delivery
ErythropoietinErythropoietinErythroidmarrow
Erythroidmarrow
IronIron
REcellsRE
cells
RE=reticuloendothelial
X
Erythropoiesis in CKD
Jan 23 2009 12:30 PM Collaborative Care of CKD 55
Anemia of CKD Primary cause: deficiency of erythropoietin
(absolute or relative)
Iron Deficiency (contributory)
Normocytic, normochromic anemia
usually starts when the GFR < 60 (Stage 3)
Jan 23 2009 12:30 PM Collaborative Care of CKD 57
Assessment of Anemia In Renal Disease
If GFR < 60 ml/min/1.73m2 (Stage 3), consider anemia of renal origin
Folate B12 Iron, saturation, ferritin R/O blood loss Erythropoietin level (?) R/O other chronic disease/inflammatory
states
Jan 23 2009 12:30 PM Collaborative Care of CKD 58NKF. Am J Kidney Dis. 2001;37:S182.
Evaluation of anemia of CKD Hemoglobin and/or hematocrit Red blood cell indices Reticulocyte count Iron parameters
Serum iron Total iron-binding capacity (TIBC) Percent transferrin saturation (TSAT) Serum ferritin
Test for occult blood in stoolGuideline 2
Jan 23 2009 12:30 PM Collaborative Care of CKD 59
Erslev. N Engl J Med. 1991;324:1339.
Clinical Consequences: untreated Anemia of CKD
Cardiovascular Left ventricular hypertrophy (LVH)
Precipitating factor for congestive heart failure (CHF)
Exacerbation of angina
Reduced Aerobic capacity
Overall well-being
Cognition
Jan 23 2009 12:30 PM Collaborative Care of CKD 60
Pre
vale
nce
of
LV
H(%
Pat
ien
ts)
0
10
20
30
40
50
>50 35 – 49 25 – 34 <2514.1 13.2 12.5 11.4 †
*
Ccr (mL/min)
Mean Hb (g/dL)
* P<0.001 †P<0.0001
Levin. Nephrol Dial Transplant. 2001;16(suppl 2):7.
Anemia and LVH
Jan 23 2009 12:30 PM Collaborative Care of CKD 61
Greaves. Am J Kidney Dis. 1994;24:768.Levin. Am J Kidney Dis. 1996;27:347.
LVH in CKD LVH is an independent predictor of cardiac
death. Hypertension, anemia, and diabetes are
modifiable predictors of LVH. Blood pressure increase of 5 mm Hg is
associated with 3% increase in LVH risk. Hb decrease of 1 g/dL is associated with 6%
increase in LVH risk.
Foley RN et al. Kidney International. 1995;47: 186-192.Levin A et al. Am J Kidney Dis. 1996;27:347-354.
Foley RN et al. Kidney International. 1995;47: 186-192.Levin A et al. Am J Kidney Dis. 1996;27:347-354.
Jan 23 2009 12:30 PM Collaborative Care of CKD 62
Chronic Kidney Disease in USACPMPM= cost per member per month
Collins. Satellite Symposium.ASN, 2000.
J Am Soc Nephrol 12: 2465–2473, 2001
Clinical and Economic Outcomes by Hematocrit Level: Incident ESRD Patients 1996–1998
<30 30 to <33 33 to <36 36 to <39 390.0
0.5
1.0
1.5
2.0
Rel
ativ
e R
atio
8760 24,465 28,674 4307 555n
reference
MortalityHospitalCost PMPM
Hct
Impact: Anemia of CKD on Outcomes
Jan 23 2009 12:30 PM Collaborative Care of CKD 63
Treatment: Anemia of CKD Recombinant erythropoietin
Epoetin alfa Darbepoetin
Iron therapy prn
Red-blood-cell transfusion severe anemia
acute anemia
Jan 23 2009 12:30 PM Collaborative Care of CKD 64
Epoetin and Management of AnemiaEpoetin and Management of Anemia
NKF. Am J Kidney Dis. 2001;37(suppl 1):S182.
NKF-K/DOQI Guidelines Target Hct 33%–36% (Hb 11–12 g/dL)* Supplement with iron to maintain target
Hct/Hb Initiate epoetin alfa (or darbopoetin)
Jan 23 2009 12:30 PM Collaborative Care of CKD 65
Erythropoietin Treatment Epoetin is administered weekly in an incremental
dose that commonly starts from 50-100units/kg SQ
Rate of rise of Hgb/Hct should be monitored weekly until the patient's condition is stable
hypertension, seizures, and venous thrombosis can occur when it rises too rapidly
Jan 23 2009 12:30 PM Collaborative Care of CKD 66Chronic Kidney Disease in USA
Epoetin Management: Monitoring
Starting dose 50–100 U/kg IV or SC qW (‘tiw’)Ensure good blood pressure controlAdjusting the dose
Reduce as Hct approaches 36% or increases by >4 points in 2 weeks
Increase incrementally if Hct does not increase by 5–6 points in 8 weeks (with adequate iron stores)
Following a dosage adjustment: Measure Hct twice weekly for at least 2–6 weeks until stable
Jan 23 2009 12:30 PM Collaborative Care of CKD 67
Correction of anemia of CKD:many positive effects Improved/increased energy, physical strength,
appetite, and sleep improved sex life, home
life, and mood improvement in vascular
resistance better immune
responsiveness to antigenic stimuli
improved cognition
Decreased shortness of breath stabilization of left
ventricular hypertrophy and possibly regression
decreased development of left ventricular dilatation
a decrease in high cardiac output
hospitalization rate, length of stay, and cost.
Jan 23 2009 12:30 PM Collaborative Care of CKD 70
Kausz. Am J Kidney Dis. 2000;36(suppl 3):S39.
St. Peter. American Society of Nephrology Meeting. 2000:A0889.
* Patients not treated with epoetin alfa.
Current Care of Anemia in Patients With CKD is Sub-optimal
Mean Hct at start of dialysis: 29%* Only 28% of patients with CKD
receive epoetin alfa before dialysis.
71
Data to Support Ideal Hemoglobin Target (1):
8 9 10 11 12 13 14 15 16
hemoglobin concentration (g/dL)
Normal Normal hematocrithematocrit
(hemodialysis)(hemodialysis)
CHOIRCHOIR
(pre-dialysis)(pre-dialysis)
1010
1414
11.311.3
13.513.5
↓ morbidity/mortality
↑ morbidity/mortality
?
Observational data, by association only
↓ morbidity/mortality
↑ morbidity/mortality
Jan 23 2009 12:30 PM Collaborative Care of CKD 72
“Epo Resistance” Poor response to Epoetin Rx
Fe deficiency Fe deficiency Fe deficiency Chronic inflammatory states Severe hyperparathyroidism Poor (inadequate) dialysis Multisystem dysfunction (hematological,
neurological, cardiac, immunological etc) Iron deficiency
Jan 23 2009 12:30 PM Collaborative Care of CKD 73
• Poor nutrition• Blood loss
Increased iron needs
NKF. Am J Kidney Dis. 2001;37(suppl 1):S182.
Iron Deficiency WithEpoetin alfa
Iron Deficiency in CKD
Preexisting Iron Deficiency
Jan 23 2009 12:30 PM Collaborative Care of CKD 74
NKF. Am J Kidney Dis. 2001;37(suppl 1):S182.Macdougall. Curr Opin Hematol. 1999;6:121.
Goodnough. Blood. 2000;96:823.
Frequently used tests
• Serum ferritin >100 ng/mL
• Transferrin saturation >20%
• Additional measurements
• Reticulocyte Hb content
• % Hypochromic RBCs
• Erythrocyte ferritin
Frequently used tests
• Serum ferritin >100 ng/mL
• Transferrin saturation >20%
• Additional measurements
• Reticulocyte Hb content
• % Hypochromic RBCs
• Erythrocyte ferritin
Target
Assessment of Iron Status
Jan 23 2009 12:30 PM Collaborative Care of CKD 75
100 mg
125 mg
1000 mg
Maximum Single Dose
100 mg x 10 doses
125 mg x 8 doses
100 mg x 10 doses
RecommendedDosage
Iron sucrose
Iron gluconate
Iron dextran
Iron Compound
NKF. Am J Kidney Dis. 2001;37(suppl 1):S182.Van Wyck. Am J Kidney Dis. 2000;36:88.
• 1 gram iron required to– Increase Hct from 25% to 35%– Maintain iron stores over 3-month period
• Recommended dose: 1 gram
Administration of IV Iron: Dosage
Jan 23 2009 12:30 PM Collaborative Care of CKD 76
Bailie. Am J Kidney Dis. 2000;35:1.Collins. J Am Soc Nephrol. 1997;8:190A.
Administration of IV Iron: Safety
Adverse Events Reported Hypotension Nausea, diarrhea, vomiting, headache,
fever Hypersensitivity reactions (anaphylaxis) Increased infectious complications
Jan 23 2009 12:30 PM Collaborative Care of CKD 77
NKF. Am J Kidney Dis. 2001;37(suppl 1):S182.Silverberg. Kidney Int. 1999;55(suppl 69):S79.
Possible Inadequacy of Oral Iron Low intestinal absorption of oral iron, even
in healthy persons Poor patient adherence Intravenous iron has improved anemia in
CKD and ESRD when oral iron has failed.
Jan 23 2009 12:30 PM Collaborative Care of CKD 78
Iron Therapy: Summary Likely need for iron during Epoetin therapy Oral iron
Ease of administration Safe Possibly ineffective
IV iron Less convenient administration Safety concerns More costly than oral iron Effective
Jan 23 2009 12:30 PM Collaborative Care of CKD 80Chronic Kidney Disease in USA Zabetakis. Am J Kidney Dis. 2000;36(suppl 3):S31.
Associated Systemic Complications in Chronic Kidney Disease (CKD)
Anemia of CKD
Hypertension
Cardiovascular disease
Dyslipidemia
Osteodystrophy
Metabolic acidosis
Malnutrition
Diabetes mellitus
Jan 23 2009 12:30 PM Collaborative Care of CKD 81
CKD Hypertension
Zabetakis. Am J Kidney Dis. 2000;36(suppl 3):S31.
Hypertension and CKD
Jan 23 2009 12:30 PM Collaborative Care of CKD 82
Coresh. Arch Intern Med. 2001;161:1207.
130/85 mm Hg
11%
27%62%
140/90 mm Hg
140/90 mm Hg
Blood Pressure Is Poorly Controlled in CKD
Jan 23 2009 12:30 PM Collaborative Care of CKD 83Chronic Kidney Disease in USA
Zabetakis. Am J Kidney Dis. 2000;36(suppl 3):S31.
Benefits of BP Control in CKD
Rate of progression of kidney disease, especially in patients with diabetes
Cardiovascular complications
Jan 23 2009 12:30 PM Collaborative Care of CKD 84
JNC VII. JAMA 2003;289:2560.
140/90 mm Hg130/80 mm Hg
Without CKDWith CKD
HTN: Goal Blood Pressure Control
Jan 23 2009 12:30 PM Collaborative Care of CKD 85
JNC VI. Arch Intern Med. 1997;157:2413.
130/85 mm Hg125/75 mm Hg
Without ProteinuriaWith Proteinuria
Blood Pressure Control in CKD: Goals
Jan 23 2009 12:30 PM Collaborative Care of CKD 86
Del Vecchio. J Nephrol. 2001;14:7.JNC VI. Arch Intern Med. 1997;157:2413.
BP Control: Interventions ACE inhibitors Angiotensin-receptor blockers (ARBs) Calcium channel blockers (CCBs) Diuretics Low-sodium diet Combination therapy
Jan 23 2009 12:30 PM Collaborative Care of CKD 87
ACE Inhibitors Recommended for Slowing the Progression of CKD
Unless contraindicated, patients with hypertension who have CKD should receive
an ACE inhibitor to control hypertension and to slow progressive renal failure
JNC VI. Arch Intern Med. 1997;157:2413.
Jan 23 2009 12:30 PM Collaborative Care of CKD 91
2° Hyperparathyroidism: Natural History
Multisystemic Toxicity1. nervous system2. cardiac3. endocrine4. immunologic5. cutaneous
Bone Disease1. osteitis fibrosa2. demineralization3. fractures4. bone pain
Calcium
1,25 Vit D Phos
Chronic Kidney Disease
PTH PTH
Jan 23 2009 12:30 PM Collaborative Care of CKD 92
Renal Osteodystrophy: Full Spectrum
Adynamic bone
Osteomalacia
Normal Mild Osteitis fibrosa
Mixed
Hyperparathyroidism
Calcium, calcitriol
Aluminium
Low boneturnover
High boneturnover
PTH ALP
PTHALPP
Jan 23 2009 12:30 PM Collaborative Care of CKD 93
Elevated PTH: Multisystemic Toxicity Widespread
systemic effects
Insidious effects
Early Diagnosis & Rx needed
* Bro AJKD November, 1997
PTHPTH
Bone RemodelingBone Remodeling
Red Blood Cell Production
Red Blood Cell Production
Cardiac FunctionCardiac Function
Neurological Function
Neurological Function
Ca, PCa, P
Jan 23 2009 12:30 PM Collaborative Care of CKD 95
Long-Term Consequences of Secondary Hyperparathyroidism
Osteitis fibrosa Vascular calcification Soft tissue calcification Calciphylaxis Resistance to vitamin D therapy Need for parathyroidectomy EPO resistance
Jan 23 2009 12:30 PM Collaborative Care of CKD 96
0.92 0.95 0.98
1.08
1.181.24
1.00
0.5
0.6
0.7
0.8
0.9
1
1.1
1.2
1.3
1.4
1.5
<50 50-100 100-150 150-300 600-900 900-1200 >1200
PTH levels & Relative Risk of Death
pg/mL Chertow ASN 2000
Jan 23 2009 12:30 PM Collaborative Care of CKD 97
Block GA, Am J Kidney Dis. 1998;31:607-617.
Higher Phosphorus: Higher Mortality Risk
1.00
1.25
1.50
1.1-4.5 4.6-5.5 5.6-6.5 6.6-7.8 7.9-16.9
Rel
ativ
e M
orta
lity
Ris
k (R
R)
Serum Phosphorus Quintile (mg/dL)
1.00 1.00 1.02
1.18*
1.39**
p=0.03
p=0.0001n = 6407
Jan 23 2009 12:30 PM Collaborative Care of CKD 98
Higher Ca P Product: Higher Mortality Risk
Block GA, et al. Am J Kidney Dis. 1998;31:607-617.
1.00
1.25
1.50
14-42 43-52 53-60 61-72 73-132
Rel
ativ
e M
orta
lity
Ris
k (R
R)
Ca × P Product Quintile (mg2/dL2)
1.06 1.08
1.13
1.34*
1.00
p=0.01n = 2669
Jan 23 2009 12:30 PM Collaborative Care of CKD 99Llach, et al. AJKD, 32,4 Supp2, 1998:S3-12
GFR, ml/m
Calcitriol, pg/ml
152535455565758595105
Intact PTH, pg/ml
100
200
300
400
CALCITRIOL PTH
P <0.01
P <0.01
When does Renal Osteodystrophy start? Calcitriol & PTH at Various Stages of CKD
0
10
20
30
40
50
n = 150
Jan 23 2009 12:30 PM Collaborative Care of CKD 100
Phosphateretention
Calcitriol Deficiency
Hypocalcemia
2º Hyperparathyroidism
Chronic Kidney Disease
Renal Osteodystrophy: CKD 3&4
Jan 23 2009 12:30 PM Collaborative Care of CKD 103
Renal Osteodystrophy: Management
↓P diet (.8-1g/d)+Fix acidosis:HCO3>22 mmol/L
Binders: P>5mg/dl: (CaCO3, Ca Acetate, Sevelamer) taken with meals
1,25 Vitamin D for low Ca + nl P (when iPTH>250 pg/mL)
Rx: calcitriol 0.25 µg/d; doxercalciferol 2.5 µg/3-7d/wk. Target iPTH 80-300(10-65 pg/mL)
Jan 23 2009 12:30 PM Collaborative Care of CKD 104
CKD stages 3&4: Acid-Base
Monitor serum bicarbonate acidosis:
HCO3>22 mmol/L
Dietary protein
Na Bicarbonate tablets or Na Acetate
Jan 23 2009 12:30 PM Collaborative Care of CKD 105
Management: Renal Osteodystrophy
Control serum phosphorus (3.0-5.0 mg/dL) Prevent or reverse accumulation of trace
substances i.e., aluminum, calcium, etc. Maintain serum calcium within normal limits
(8.5-9.6 mg/dL) Suppress secondary hyperparathyroidism
using vit D or analogs Prevent the development of parathyroid
hyperplasia Avoid over suppression of PTH (adyn bone dx)
Jan 23 2009 12:30 PM Collaborative Care of CKD 106
Target Values
Phosphorus: 3.0 - 5.0 mg/dL – ideal
Calcium: normal range ( 8.5-9.6 mg/dL)
Ca X P: < 55
PTH: 150 - 300 pg/ml
Jan 23 2009 12:30 PM Collaborative Care of CKD 107Chronic Kidney Disease in USA Zabetakis. Am J Kidney Dis. 2000;36(suppl 3):S31.
Associated Systemic Complications in Chronic Kidney Disease (CKD)
Anemia of CKD
Hypertension
Cardiovascular disease
Dyslipidemia
Osteodystrophy
Metabolic acidosis
Malnutrition
Diabetes mellitus
Jan 23 2009 12:30 PM Collaborative Care of CKD 154
Questions?
NKF: www.kidney.orgNKF-Va: www.kidneyva.org NKDEP www.nkdep.nih.gov