Chronic Kidney Disease:
A Silent Epidemic (Part 1)
Naima Ogletree, MSN, APRN, BC
Nephrology & Hypertension
Henry Ford Health System
Objectives
• Define CKD: prevalence,
epidemiology, and risk factors
• Discuss occurrence of complications
and co-morbid conditions of CKD
• Describe treatment guidelines
2
Kidney Anatomy
• Normal adult kidney is 11–12 cm long;
Wt: 125–170 g
• Left kidney > Right kidney in size,
male > female; located at T12 to L3
• The kidney (a bean-shaped structure) is
composed of: parenchyma and the collecting
system. Parenchyma consists of the renal
cortex and inner medulla. The collecting
system includes the calcyces that form the
renal pelvis that drains into the ureters
• Kidneys are usually perfused by a single
renal branching artery
3
Physical Location of Human
Kidney
LEFT KIDNEY
URETER
BLADDER
4
Anatomy of the Kidney
FIBROUS CAPSULE
CORTEX
PYRAMID
PAPILA
RENAL CALYX
RENAL PELVIS
RENAL ARTERY
RENAL VEIN
URETER
5
Microscopic Anatomy
• There are 300,000 to 1,200,000
nephrons (basic structure and
functional unit of the kidney) in a
single kidney
• Glomeruli, loop of Henle, proximal
and distal tubule compose the
nephron
6
A MICROSCOPIC LOOK AT
THE RENAL CORTEX
GLOMERULUS
7
Glomerulus Anatomy
8
Basic Concepts of the Kidney
• Regulatory function: Controls composition
and volume of the body fluids
• Maintains acid-base balance by varying the
excretion of water and solutes
• Endocrine function: producing several
hormones:
- renin
- erythropoietin
- active vitamin D3
- prostaglandins, adenosine, etc
9
Basic concepts of the Kidney
• Excretory function: removes various
nitrogenous metabolic end products in
urine. For example, the kidneys filter blood
through the glomerulus forming an
ultrafiltrate.
• As the ultrafiltrate passes through the
kidney, reabsorption of essential products
and secretion of unwanted products occur.
10
DYSFunction of the Kidney
• Disrupts “HOMEOSTASIS”.
 Excretion of waste products of metabolism.
 Water electrolyte and acid base balance.
• Disrupts HORMONAL FUNCTION.
 Erythropoietin.
 Vitamin D3
 Renin, prostaglandins, angiotensinogen 2, nitric
oxide , endothelin and bradykinin
 Miscellaneous:
• Gluconeogenesis
11
CKD: Background
• Common disorder
 Less common than HTN
 More common than diabetes
• Progressive disorder
 Underdiagnosed
 Undertreated … due to lack of agreement
of its definition and staging
Kidney/Dialysis Outcomes Quality Initiative. Am J Kidney Dis. 2002;40:S1–S246.
12
Chronic Kidney Disease (CKD)
• Includes all types and levels of kidney
dysfunction

Avoid usage of “CRI” and “CRF,” which do not
indicate severity of dysfunction
• CKD is not etiology-specific and causation
must always be pursued

CKD from “diabetic nephropathy”

CKD from “hypertensive nephrosclerosis”

Membranous nephropathy
Kidney/Dialysis Outcomes Quality Initiative. Am J Kidney Dis. 2002;40:S1–S246.
13
Overview of CKD
Epidemiology of CKD
 20 million adults in the United States
 Millions more at risk:
• Aging population
• Increasing prevalence of diabetes mellitus
• Increasing prevalence of hypertension
14
CKD: Care is Costly
CKD
Care
Total NIH
Budget
$19.3
Billion/Yr
CKD Accounts for 6%
of Medicare Payments
$17.8
Billion/Yr
Lost Income for pts is
$2–4 Billion/Yr
TH Hostetter, National Kidney Education Program, 2003.
15
CKD: Prevalence by NHANES III
7.6
5.9
5.3
0.4
0.3
J Coresh, et al. Am J Kidney Dis. 2003;41(1):1–12
16
Endstage Renal Disease (ESRD)
• ESRD
 Medicare term — permits federal
reimbursement
 Pt requires renal replacement therapy for
survival
• Hemodialysis
• Peritoneal dialysis
• Kidney transplantation
Kidney/Dialysis Outcomes Quality Initiative. Am J Kidney Dis. 2002;40:S1–S246.
19
ESRD: Increasing Problem
•
•
*Data
 ESRD incidence, prevalence, cost

Pts living longer

Increased prevalence of diabetes

Prevalence in 2003, 300,000+ pts

Projection for 2010, 600,000 pts
Wayne Co., MI — highest prevalence of
ESRD per capita of all U.S. counties*

1079 of 3093 new starts in MI, 2001

3913 of 9913 prevalent pts in MI, 2001
on file: National Kidney Foundation of Michigan, 2002.
20
ESRD: Disease of the Elderly
148,508
125,280
55,105
26,177
5961
n=361,031
United States Renal Data System (USRDS) 1997 Annual Data Report.
21
ESRD:  Risk by Ethnicity
Racial Differences in ESRD in U.S. from 1990–1998
5
4.45 *
3.57 *
Odds Ratio
4
3
2
1
1.59 *
1.00
reference
0
White
Black
Native
Asian
*P <0.0001
United States Renal Data System (USRDS) 2000 Annual Data Report •
WWW.USRDS.ORG.
22
ESRD: Prevalence by Ethnicity
70
62
60
NA
Asian
AA
C
50
40
31
32.6
30
20
10
12.7
2
3
3.8
0.9
0
ESRD
Census
Percent (%) of Category
Abbrev: NA, Native American; AA, African-American; C, Caucasian.
n = 361,031
United States Renal Data System (USRDS) 1997 Annual Data Report.
23
ESRD: Incidence by Ethnicity
P a t ie n t s p e r m ill io n p o p u la t io n
Racial Differences in ESRD in U.S. from 1990–1998
800
W h ite
B la ck
N a tive
A sia n
600
400
200
0
1990 1991 1992 1993 1994 1995 1996 1997 1998
Year
United States Renal Data System (USRDS). 2000 Annual Data Report •
WWW.USRDS.ORG.
24
ESRD:  Incidence and Prevalence
Incidence of New Patients
100,000
Greatest Increase from Diabetic ESRD
All ESRD
80,000
60,000
40,000
Diabetes
20,000
Hypertension
Glomerulonephritis
0
1989 1990 1991 1992 1993 1994 1995 1996 1997 1998
Diabetes is the most common cause in Caucasians, Hispanics, Asians, and overall.
Among African-Americans, hypertension is the most common cause of ESRD.
US Renal Data System, 2000 Atlas of ESRD in the United States.
25
ESRD: Racial Distribution for
Comorbidities in Dialysis (1999)
Percent of Patients
100
80
Black
Asian
Native
White
60
40
20
0
History of
Hypertension
Diabetes§
Congestive
Heart Failure
Diabetes‡
Insulin
Treated
§ Diabetes mellitus as a primary diagnosis or contributing diagnosis.
‡ Diabetes mellitus that requires insulin treatment, which is a subset of the diabetes category.
United States Renal Data System (USRDS) 2000
Annual Data Report • WWW.USRDS.ORG
26
Overall Rates of
Hospitalization
Inpatient Days among
Elderly Medicare Pts
with CKD in the
United States.
Am J Kidney Dis. 2003
Nov;42(5):972-81
27
GFR and Hospitalization
Age-Standardized Rate of
Hospitalization (per 100
person-yr)
Age-Standardized Rates of Hospitalization
160
140
120
100
80
60
40
20
0
144.61
86.75
45.26
13.54
17.22
>=60
45-49
30-44
15-29
<15
Estimated GFR (mL/min/1.73 m2)
Go et al. New Engl J Med. 2004;351:1296-1305.
28
Change in FOCUS
CKD
2
3
4
29
CKD Becomes the Focus
• Rationale for Initiative
1. CKD is a public health problem.
2. Economical, effective testing
methods and therapies exist.
3. Testing and therapy are
inadequately applied.
BA Boissonault. Niagara Health Quality Coalition, 2003.
L Smith-Wheelock. National Kidney Foundation of Michigan, 2003.
30
Timely Referral Keeps pts Out of
the Red Zone
NKF CKD Stage by MDRD GFR Equation
1
2
3
4
REFER
E
TO
S
KIDNEY
R
DOCTOR
D
Refer in Stage 1 or 2:
• Uncontrolled HTN
• Hematuria
• Proteinuria
• Structural lesion
NORMAL AGE DECLINE
120
90
5
60
30
15
GFR (mL / min / 1.73 m2)
Kidney/Dialysis Outcomes Initiative. Am J Kidney Dis. 2002;39:S1–S266.
31
CKD: Early CKD Treatment
Preserves Kidney Function
100
75
GFR
50
25
10
4
7
9
11
Time (yr.)
TH Hostetter, National Kidney Disease Education Program, 2003.
32
CKD Complications
Evolution and Acceleration by Stage
Affected 100
pts
80
(%)
Hypertension
Hyperparathyroidism
60
Anemia (Hgb < 12 g/dl)
Phosphorus > 4.5 mEq/L
40
Fail quarter mile walk
20
Hypoalbuminemia
(Alb < 3.5 g/dl)
0
1
2
3
4
CKD Stage
DM, ARF: CKD complications may occur earlier
33
34
CKD: Three-Fold Initiative
1. Screen and prevent CKD in pts who
are at-risk
2. Develop an early CKD identification
process
3. Establish a collaborative disease
management model for internists,
family practitioners, and
nephrologists
35
Detection 0f pts at Risk
Measures of Kidney
Function
Markers of
Kidney Damage
Other Physiologic
Markers
Serum creatinine
Microalbuminuria
Hemoglobin/hematocrit
BUN
Overt proteinuria
Total cholesterol
Creatinine clearance
Triglycerides
GFR
Calcium/phosphorus
Intact parathyroid hormone
Serum bicarbonate
Serum electrolytes
Albumin
BUN = blood urea nitrogen; GFR = glomerular filtration rate.
Pereira. Personal communication.
36
CKD: Screening and Prevention
•
Identify at-risk medical populations

Hypertension

Diabetes

Metabolic syndrome

1st degree relatives of ESRD pts
•
CKD history often neglected during Hx
•
Identify at-risk ethnic groups

Hispanics

African-Americans

American Indians (Native Americans)
United States Renal Data System (USRDS) 2000 Annual Data Report •
WWW.USRDS.ORG.
37
CKD: High-Risk Groups
• Diabetics with urine Alb:Cr ratios
>30 mg Alb/1 g Cr
• Non-diabetics with urine Alb:Cr ratios
>300 mg Alb/1 g Cr
• Non-diabetics with MDRD GFR
<60 mL/min/1.73 m2
Kidney/Dialysis Outcomes Initiative. Am J Kidney Dis. 2002;39:S1–S266.
38
CKD: Screening and Prevention
• Screening at-risk pts

Biochemical profile

Urinalysis with microscopic exam

Urine protein (albumin)
determinations

MDRD GFR estimation
39
CKD: Three-Fold Initiative
• Screening of pts at-risk for CKD
2. Development of an early CKD
identification process
• Establishment of a disease
management protocol between
internists and family practitioners
and nephrologists
40
CKD: Evolution of GFR Estimating
Methods
BUN
SCr
24-h CrCl
Highly
Insensitive
For CKD
Detection
Cockroft
Gault Eqn
MDRD
GFR Eqn
Estimates raw
CrCl, not GFR
Overestimates GFR
Unnecessary test
A Akbari, et al. Arch Intern Med. 2003;163:356–360.
S Klahr, et al. MDRD Study Group. N Engl J Med. 1994;330:877–884.
Validated
Best choice
41
CKD: MDRD GFR
•
•
Multi-variable equation

Demographics: Age, Gender, Ethnicity

Biochemical: Albumin, SCr, BUN
Validated in 577 pts

By iothalamate clearance

For GFRs 30–90 mL/min/1.73 m2
• MDRD GFR Eqn. 7 (mL/min/1.73 m2)
= 170  SCr–0.999  Age–0.176  BUN–0.17  Alb0.318
 0.762 (female) ;  1.18 (African-American)
Kidney/Dialysis Outcomes Quality Initiative. Am J Kidney Dis. 2002;39:S1–S266.
G Manjunath, et al. Postgrad Med. 2001;110(6):55–62.
42
CKD: Classification by MDRD GFR
• Rationale for use

GFR — direct measurement of kidney
function

GFR — best index of kidney function in
health and disease

GFR — correlates with pathologic
severity of disease

GFR — correlates functional level with
risks of CKD progression and
development of CV disease
G Manjunath, et al. Postgrad Med. 2001;110(6):55–62.
43
CKD: NKF Definition
• Disorder must be >3 mo duration
 MDRD GFR <90 mL/min/1.73 m2 or
 GFR >90 mL/min/1.73 m2 with either
• Parenchymal abnormality (cyst, scar) or
• Hematuria (>4 RBCs/hpf) confirmed by
microscopical examination on 2 occasions or
• Proteinuria (2 occasions, 1 mo apart)
o
o
o
o
Dipstick
Pro:Cr ratio
Alb:Cr ratio
24-h collection
2+ or 100 mg/dL
1.0 (Pro and Cr in mg/dL)
500 mg/g
1.0 g/24-h/1.73 m2
S Klahr, et al. N Engl J Med. 1994;330:877.
Kidney/Dialysis Outcomes Quality Initiative. Am J Kidney Dis. 2002;39:S1–S266.
44
CKD: Normal Kidney Function
• MDRD GFR >90 mL/min/1.73 m2 and
all of the following
 No hematuria
 No proteinuria
 No parenchymal or structural
abnormality (cyst, scar, hydronephrosis)
Kidney/Dialysis Outcomes Initiative. Am J Kidney Dis. 2002;39:S1–S266.
45
CKD: Age-Related Decline in GFR
• Age-related declines in GFR occur
 Should not be considered “disease”
 GFR 60–89 mL/min/1.73 m2
 Do not refer pt to nephrologist if GFR is
stable and all of the following
• No proteinuria
• No hematuria
• No structural lesion(s)
Kidney/Dialysis Outcomes Initiative. Am J Kidney Dis. 2002;39:S1–S266.
46
NKF CKD Stages 1–5
Stage
Description
GFR
1
Chronic kidney damage
with normal or  GFR
> 90
2
Mild  GFR
60–89*
3
Moderate  GFR
30–59
4
Severe  GFR
15–29
5
Kidney failure
<15 or dialysis
GFR: mL/min/1.73 m2
*May be normal for
age
Staging Classification
Kidney/Dialysis
Outcomes
Initiative. Am J Kidney Dis.Prepublished
2002;39:S1–S266.
47
CKD: Screening and Prevention
Summary
•
Use MDRD GFR not SCr
•
“Spot” urine Alb:Cr ratio

Collect specimen at 0600–1200 hours

24-h urine collection, no longer required
•
Screenees?

GFR <90 mL/min/1.73 m2
•
Not from age-related decline

Hypertension

Diabetes — annual testing

FH of CKD — less frequently, if normal

Hematuria

Edema of unknown cause
G Manjunath, et al. Postgrad Med. 2001;110(6):55–62.
48
CKD: Three-Fold Initiative
• Screening for and prevention of CKD
in pts at-risk for CKD
• Development of an early CKD
identification process
3. Establishment of a collaborative
disease management model between
internists and family practitioners
and nephrologists
49
CKD: Under-recognized Problem
• Patients unaware
 Only 13% of pts with CrCl <60 mL/min or
+1 dipstick proteinuria aware of their CKD
 Only 8% of pts with “known CKD” aware of
their CKD, despite recent physician visit
• Implications
 Physicians require more CKD knowledge
 “Late” referral of pts with advanced CKD to
nephrologists, e.g., African-American men
Am J Kidney Dis. 2002;40:1173–1178.
50
CKD: Under-recognized Problem
• Only 10% of Medicare beneficiaries
with diabetes receive annual urine
albumin tests
• Less than 1/3 of hospitalized CKD pts
with proteinuria are prescribed an
ACEI at discharge
Medicare data on file: WM McClellan, et al. Am J Kidney Dis. 1997;29:368.
51
CKD: Survey of PCPs
52
CKD: Delayed Referral to Nephrologist
A Stack. Am J Kidney Dis. 2003;41:310–318.
53
CKD: Reasons for Delayed Referral
to Nephrologist
• CKD is under-recognized
• Failure to screen pts at-risk
• Fear of loss of control over pt
• PCPs unaware of incremental benefits of
earlier referral

Fewer ER visits (pulmonary edema)

Significant healthcare cost savings
• Lack of education regarding CKD
management
R Sesso, AG Belasco. Nephron Dial Transplant. 1998;11:2417. DW Eadington. Nephron Dial
Transplant. 1996;11:2124-2126. RJ Schmidt, et al. Am J Kidney Dis. 1996;32:278–283. P Jungers,
et al. Kidney Int. 1993;41:S170–S173.
54
CKD: Consequences of Delayed
Referral
Time to Referral
Parameter
>4 mo
<4 mo
Malnutrition (%)
15.8
21.1
Albumin (g/dl)
3.53
3.41
Hct at Referral (%)
30.7
29.8
32
10.5
Received Vascular Access (%)
40.8
22.6
Access Type (AVF; AVG) (%)
14.5; 26.3
5.7; 16.9
—
68; 23
Tx with EPO (%)
Death Risk  at 1- and 2-Yr (%)
A Stack. Am J Kidney Dis. 2003;41:310–318.
Late referral means <4 mo between time of initial Nephrology consultation and dialysis.
AVF, arteriovenous fistula; AVG, arteriovenous graft.
55
CKD: Delayed Referral Results in
Higher Medical Costs in Early ESRD
Source: BA Boissonault for the Niagara Health Quality Coalition, 2003.
56
Advanced CKD Substantially
Impairs Quality of Life
Sickness Impact Profile (SIP)
Work
Note: Higher scores
indicate poorer QOL.
Eating
Recreation/pastime
Home management
Sleep/rest
Psychosocial
CRI pts (N = 38)
Reference group
Physical
Overall SIP
0
5
10
15
20
25
SIP Score
Klang et al. Quality of Life Research. 1996;5:109-116.
57
Ultimate Goal
Delay CKD Progression
• Diagnose / treat comorbid conditions
• Evaluate / treat CVD
• Iatrogenic risks @ CKD Stage 3
 protect against further insults (e.g., ARF)
PREVENT & STABILIZE
CKD STAGE 4
— A Clinical Event —
58
CKD: ARF Prevention
• Rationale for Intervention
 ARF — often preventable
 ARF — produces residual kidney
damage, i.e., CKD
 CKD pts — at higher risk for ARF
PA McCullough, et al. Am J Med. 1997;103:368–375
L Gruberg, et al. J Am Coll Cardiol 2000;36:1542–1548
59
CKD: Increased Risk for ARF
• ECF volume depletion — fosters ARF
• High-risk groups

DM, types 1 and 2

Non-DM CKD Stage 3–5 (i.e., GFR <60)*

Liver failure

Heart failure

CV operations

Radiocontrast procedures
E Nikolsky, et al. Rev Cardiovasc Med 2003;4(Suppl 1):S7–S14.
*Data extrapolated from multiple studies
60
Avoid Iatrogenic Injury
AVOID NEPHROTOXINS
•
NSAIDs, AGs, Amphotericin B
•
Radiocontrast
1. Stop diuretics 3–4 d before procedure
2. ECF volume expansion
(preferably with HCO3 ?)
3. N-Acetylcysteine (SCr dependent)
M Tepel, et al. NEJM, 343:180–184, 2000
C Caputo, et al. AJKD Dis 39:A14, 2002 (abstract)
61
Acute Renal Failure: NSAID-Induced
Afferent Arteriolar Constriction
Paff
NORMAL
PGC
Peff
 RAA
NSAID
Paff
PGC
Peff
VA Valentini, et al. Arch Intern Med. 1991;151:2367–2372.
RAA, afferent arteriolar resistance.
62
NSAIDS
• NSAIDs (COX-1/-2 inhibitors) lower GFR,
retain sodium and may cause hyperkalemia
• People with an activated Renin-AngiotensinAldosterone system are especially at risk
for NSAID-induced ARF
 Advanced age
 Hypertension
 Diabetes
 Dehydration
 Concomitant diuretic use
63
CKD: Radiocontrast-induced
Nephropathy
• Common complication in CKD and other
high risk groups
• Significant morbidity and / or mortality

Event-free survival is  by contrast nephropathy

In-hospital mortality  by contrast nephropathy
• Preventable, modifiable
R Solomon, et al. N Engl J Med 1994;33:1416–1423.
NE Lepor. Rev Cardiovasc Med 2003;4(Suppl 1):S15–S20.
64
65
CKD: Radiocontrast-induced
Nephropathy
• High-risk groups

CKD of any cause

Advanced age

Diabetes

Nephrotoxin co-administration
•
NSAID (not aspirin)
•
Diuretics
•
ACEI, ARB
•
Aminoglycosides
•
Cyclosporine, tacrolimus
•
cis-platinol
R Solomon, et al. New England Journal of Medicine. 1994;331:1416–20.
66
CKD: Radiocontrast-induced
Nephropathy Prevention
•
•
•
Nephrotoxins

Stop diuretics, ACEIs/ARBs, NSAIDs

Avoid aminoglycosides, amphotericin B
Prophylaxis

Normal saline to expand ECF volume, unless edema
is present

N-acetylcysteine
Preferred contrast media

Non-ionic, low osmolar contrast

Iso-osmolar agents, if available
R Solomon, et al. N Engl J Med 1994;33:1416–1423
NE Lepor. Rev Cardiovasc Med 2003;4(Suppl 1):S15–S20
67
Recommendations for Common Interventions Used to
Prevent Contrast-medium-induced Nephropathy
IV saline
therapy
0.9% saline at
1 mL/kg/h for
24 h, start 12 h
pre-contrast
delivery
Small randomized
trials: iv saline vs
oral fluids;
shorter regimens
of iv fluids; and
0.45% saline
Optimal
duration of iv
therapy not
fully
established by
existing trials
RECOMMENDED
Avoid ECF
volume
depletion
Optimize HF
125 mL/h NSS
Contrast
Medium
Low
osmolality,
lowest dose
possible
Meta-analysis
of many RCTs
comparing low
to high
Isosmolar
contrast may be
less risky in high
risk pts, more
data required
Low osmolality
medium
IV Sodium
Bicarbonate
154 mmol/L at
3 cc/kg/h
before contrast,
then 1 mL/kg/h
for 6 hours
after
Single RCT
showed lower
risk of 25%
increase of SCr v
0.9% saline at
same
rate/duration
Methodologic
flaws in trial
Not generally
recommended,
need further
trials to
confirm
efficacy
N-acetyl
600 mg po
q12 h × 4,
starting before
contrast
delivery
Multiple RCTs
Inconsistent
trial results,
optimal dose
not clear
Recent highdose study
shows benefit
in angioplasty
cysteine
Meta-analyses
Lowest
contrast
volume
68
CKD: Preventing Progression
• Attain glycemic control in DM
• Attain BP target
• Block RAAS
• Treat anemia of CKD
• Treat associated CVD and dyslipidemia
• Prevent renal osteodystrophy (ROD)
• Prevent ARF and avoid nephrotoxins
• Optimize nutrition
ME Rosenberg. Chronic Kidney Disease: Progression in NephSAP. Ed. RJ Glassock.
2003;2(3):85–111.
69
Chronic Kidney Disease (CKD)
• Generic
 Any kidney disorder
 Does not replace specific disorders
 CKD, secondary to ________
• Stratified into Stages by GFR
 Complications stratification
 Morbidity stratification
 Guides intensity of therapy
70
CKD Guidelines for Treatment
• National Kidney Foundation’s Kidney
Disease Outcomes Quality Initiative
(NKF KDOQI)
• Based heavily on Evidenced Based
Medicine
• Offers opinions that guide treatment
71
ALL of the above plus:
• Develop clinical action plan for each patient, based on disease stage as defined by the
National Kidney Foundation, Kidney Disease Outcomes Quality Initiative (K/DOQI) [B]
• Incorporate self-management behaviors into treatment plan at all stages of CKD [B]
72
NKF Guidelines address
domains of CKD care
73
NKF Guidelines address
domains of CKD care
Periodic
eGFR
74
Decrease CV Disease Risk Factors
75
CKD: CVD Prevention Strategies
— Level of Evidence
Lipid tx (B,C)
Exercise (C)
Wt loss (B)
Aspirin
Folic acid (C)
Smoking (B)
Large RCTs that involve CV risk prevention
strategies in CKD have not been performed.
76
Major Cause of Death in CKD
Cardiovascular Disease
Shulman et al. Hypertension. 1998;13(supple 1):I-80–I-93.
77
CKD: CVD Risks
• CVD risk  1.4–2.05X if
SCr >1.4–1.5 mg/dL
• CVD risk  1.5–3.5X with microalbuminuria
• First-year CVD mortality of CKD (3.5%)
increases 5-fold (17%) with addition of
diabetes
• Annual CVD 10–100X in ESRD
Multiple Sources: J Flack, et al., 1993. AS Levey, et al., 1998. Jensen, et al., 2000.
Ruilope, et al., 2001. JFE Mann, et al. 2001. AS Collins, et al., 2002.
78
Cardiovascular Health Study: “Even Mildly
Elevated SCr Increases CV Disease (CVD) Risk.”
Parameter
Normal S Cr
High S Cr
CVD
13.0
35.8
Overall
29.5
76.7
CVD
31.8
54.0
Stroke
11.9
21.1
CHF
17.0
38.7
Mortality (per 1000 pt-yr
pt
Incident (per 1000 pt-yr)
pt
Kidney/Dialysis Outcomes Initiative Clinical Practice Guidelines for Managing
Dyslipidemias in Chronic Kidney Disease. Am J Kidney Dis. 2003;41(Suppl 3):S1–S91.
79
CKD: CVD Comorbidities (1999)
§ Diabetes mellitus as a primary or contributing diagnosis.
‡ Diabetes mellitus that requires insulin treatment, which is a subset of the diabetes category.
80
CV Mortality in General Population
(GP) & Dialysis pts by Ethnicity
Annual % Mortality (Log Scale)
100.000
10.000
1.000
0.100
GP Black
GP White
Dialysis Black
Dialysis White
0.010
0.001
25-34
35-44
45-54
55-64
65-74
75-84
85+
Age (years)
MJ Sarnak, AS Levey. Semin Dial. 1999;12:69–76.
81
Cardiovascular Health Study: “Even Mildly
Elevated SCr Increases CV Disease (CVD) Risk.”
• Rationale for Intervention
 CV mortality is higher in CKD than
general population
 ~50% of ESRD pts die from CVD
 Death before CKD Stage 5/ESRD is common
 CVD inherent in CKD
• CV risk: CKD + 30 y.o. = 75 y.o. non-CKD
• CKD is “CHD/diabetic equivalent”
• CKD is pro-inflammatory
Kidney/Dialysis Outcomes Initiative Clinical Practice Guidelines for Managing
Dyslipidemias in Chronic Kidney Disease. Am J Kidney Dis. 2003:41(Suppl 3):S1–S91.
82
Decrease CV Risk Factors
• Strict BP control
• Tight glycemic control
• Use anti-RAAS drugs
• Lipid control
• Correct anemia
83
Hypertension & CKD
84
Guideline: Hypertension
1.1
Antihypertensive therapy should be used in CKD to:
1.1.a. Lower blood pressure (A);
1.1.b. Reduce the risk of CVD, in pts with or without hypertension (B)
1.1.c. Slow progression of kidney disease, in pts with or without
hypertension (A)
1.2
Modifications to antihypertensive therapy should be considered
based on the level of proteinuria during treatment (C)
1.3
Antihypertensive therapy should be coordinated with other
therapies for CKD as part of a multi-intervention strategy (A).
1.4
If there is a discrepancy between the treatment recommended
to slow progression of CKD and to reduce the risk of CVD,
individual decision-making should be based on risk
stratification (C).
JNC 7 Reclassification of BP
Based on Risk
JNC VI
JNC 7
BP (mm Hg)
BP (mm Hg)
Optimal
<120/80
Normal
120-129/80-84
Borderline
130-139/85-89
Normal
<120/80
Prehypertension 120-139/80-89
Hypertension
Stage 1
140-159/90-99
Stage 2
160-179/100-109
Stage 3
≥180/110
Stage 1
140-159/90-99
Stage 2
≥160/100
Source for JNC VI: Arch Intern Med. 1997;157:2413-2446.
Adapted from Chobanian AV, et al. Hypertension. 2003;42:1206-1252.
87
HTN Treatment by JNC 7
HTN w/ No
Compelling Indications
Stage 1 HTN
Stage 2 HTN (SBP
(SBP 140-159 or
DBP 90–99 mmHg)
≥160 or DBP ≥ 100
mmHg)
Thiazide
diuretic for most
2-drug combo
for most
Consider
Usually thiazide +
ACEI, ARB,
β-blocker, or CCB
ACEI, ARB,
β-blocker, CCB
or combination
Chobanian AV, et al. The JNC 7 Report. JAMA. 2003;289:2560-2572.
Compelling indications: CHF, post-MI, high risk of CAD, DM, CKD, stroke, migraine …
C(KD)ompelling
Indications
Drug(s) for
compelling
indications
Other BP drugs
(thiazide + ACEI,
ARB, β-blocker, CCB)
as needed
88
BP Targets in Diabetic and Nondiabetics
with Kidney Disease
Type of Kidney
Disease
BP Target
(mm Hg)
Preferred Agents
for CKD, with or
without HTN
Other Agents to
Reduce
CVD Risk and Reach
BP Target
ACE inhibitor
or ARB
Diuretic preferred,
then BB or CCB
Diabetic CKD
Nondiabetic CKD
UPC 200 mg/g
SBP
<125–130
Nondiabetic CKD
UPC <200 mg/g
CKD in TX Recipient
Diuretic preferred,
then ACEI/ARB,
BB or CCB
DBP
<75–80
None preferred
CCB, diuretic, BB,
ACE inhibitor, ARB
Am J Kidney Dis, May (Suppl.), 2004
89
HTN Treatment in CKD
Diabetic or Nondiabetic
90
Hypertension in CKD
• Rationale for Intervention
 Elevated BP worsens CKD
 GFR declines faster with HTN
• Rapid decline rate is >4 ml/min/1.73 m2/yr
• Target BP
 <130/80 mmHg if proteinuria <1 g/d
 <125/75 mmHg if proteinuria >1 g/d
91
BP Control Prevents CKD
Progression
MAP (mm Hg)
95
98
101
104
107
110
113
116
119
0
r=0.69; P<.05
-2
-4
GFR
Decline -6
Untreated
HTN
(mL/min/y)
-8
-10
-12
130/85
140/90
-14
GFR, glomerular filtration rate; HTN, hypertension; MAP, mean arterial pressure.
Adapted from Bakris GL et al. Am J Kidney Dis. 2000;36:646-661.
92
Hypertension & CKD
Optimal BP Control
•
No edema

•
•
Limit daily sodium intake
•
6 gm NaCl (102 mEq)
•
2400 mg sodium (104 mEq)
Diuretics

GFR >40 ml/min/1.73 m2, HCTZ

GFR <40 ml/min/1.73 m2, loop agent
RAAS blockade

ACEI

ARB
93
Benefits of BP Therapy
General Population
Male
Biennial age-adjusted rate
per 1000 pts at risk
50
Female
50
45.4
40
40
Normotensive
Hypertensive
30
30
22.7
21.3
20
20
13.9
12.4
9.9
10
3.3
5.0
10
7.3
6.2
3.5
0
RR Ratios:
9.5
2.4
0
2.0
6.3
2.1
CAD
Stroke
PAD
CHF
CAD
Stroke
PAD
CHF
2.0
3.8
2.0
4.0
2.2
2.6
3.7
3.0
CAD = coronary artery disease, PAD = peripheral artery disease; CHF = congestive heart failure.
Adapted from: Kannel WB. JAMA. 1996;275:1571-1576.
94
Hypertension and CKD
Multiple Drugs Required
UKPDS (<85 mm Hg, diastolic)
Type 2 DM
MDRD (<92 mm Hg, MAP)
Nondiabetic Kidney Disease
HOT (<80 mm Hg, diastolic)
DM Subgroup Analysis
AASK (<92 mm Hg, MAP)
African Americans, No DM
RENAAL (<140/90 mm Hg)
Type 2 DM Nephropathy
IDNT (135/85 mm Hg)
Type 2 DM Nephropathy
1
MAP = mean arterial pressure.
2
3
4
Number of BP Medications
Bakris G, et al. AJKD. 2000;36:646-661; Brenner BM, et al. NEJM. 2001;345:861-869.
Lewis EJ, et al. NEJM. 2001;345:851-860.
95
96
Glycemic Control
97
T2DN
Global Perspective
Diabetes (DM) affects more than
170 million people worldwide
•
Number will rise to 370 million by 2030
•
About 1/3 of affected will eventually
develop progressive renal deterioration
•
Microalbuminuria (MA) develops in
2–5% of pts per year
98
98
Epidemiology of Diabetes
• 19 million persons

0.5 million type 1 DM

Remainder, type 2
• Over-representation in ESRD population
worldwide
• Over-representation in U.S. ESRD
population
• Incidence increasing with rate of obesity
99
100
Global Estimates and Projections
for Incidence of Diabetes Mellitus
Type II Diabetes
25
250
20
200
15
In Millions
In Millions
Type I Diabetes
10
5
0
150
100
50
1997
2010
0
Year
1997
Year
2010
A Amos, et al. Diabetes Medicine. 1997;14[Suppl 5]:S1-85.
101
NEW ESRD: Incidence from DM
Number of People
35,000
30,000
25,000
20,000
15,000
10,000
5,000
0
1984
1986
1988
1990
1992
1994
1996
Year
Centers for Disease Control Diabetes Surveillance, 1997.
102
Predictions Regarding T2DM
A. Year 2000 and beyond
 One of three newborns will develop type
II diabetes as an adult
 One of two newborns, Hispanic or African
American, will develop type II diabetes as
an adult
B. Year 2050
A. U.S.: 4550 million will develop T2DM
C. Implications for CKD and RRT uncertain
Dr. KM Venkat Narayan
103
“… it appears that there is an emerging
pediatric epidemic of type 2 diabetes. If
this epidemic cannot be averted, its full
public health effect will be felt as affected
children become adults and the longterm complications of diabetes develop.”
New Engl J Med 2002:346(11)
104
ESRD: Etiology by 1° Diagnosis
Other
10%
DM
50%
GN 13%
HTN
27%
United States Renal Data System (USRDS) 2000 Annual Data Report •
WWW.USRDS.ORG.
105
First-year mortality rates,
by CKD & diabetic status
General Medicare patients age 67 & older; rates adjusted for age, gender, & race, & determined
for the first year after the cohort-defining period. Reference population: 1999–2000 cohort.
106
Natural History of Diabetic Nephropathy
Insulin resistance syndrome
Clinical type 2 diabetes
Functional changes*
Rising blood pressure
Structural changes†
Microalbuminuria
Proteinuria
Rising serum
creatinine levels
End-stage
renal disease
Cardiovascular death
-1
2
5
10
20
30
Years
107
Glomerulus: Site of Hyperfiltration
in Diabetes and Obesity
108
109
Diabetic Glomerulosclerosis
110
Glycemic Control Retards
Progression of CKD
Retinopathy
Nephropathy
Neuropathy
Microalbuminuria
Relative Risk
15
13
11
9
7
50%
Reduction
5
3
1
6
7
8
9
10
11
12
A1C (%)
*Based
on Diabetic Control and Complications Trial data
Adapted with permission from Skyler JS. Endocrinol Metab Clin North Am. 1996;25:243
111
HbA1c: Delay DN
OHKUBO TRIAL (1995)
• Hypothesis: Development of
nephropathy is decreased by intensive
insulin therapy
• Primary and secondary prevention
study
 6-mo F/U intervals for 6 yr
Glycemic Control
112
HbA1c: Delay DN
MIT
CIT
55
55
Primary
7.7%
28%
Secondary
11.5%
32%
Number (N)
Glycemic Control
113
HbA1c: Delay DN
REQUIREMENTS
• HbA1C
6.5%
• FBS
110 mg/dl
• 2-h PPG
180 mg/dl
Glycemic Control
114
HbA1c: Delay DN
EUGLYCEMIA
• Partially reverses glomerular hypertrophy
and hyperfiltration
• Type 1 DM — delays onset of
microalbuminuria
• Kidney-Pancreas transplant — pancreatic
transplant prevents recurrent
nephropathy in allograft kidney
Fioretto, et al. New Engl J Med 339:69–75, 1998
115
HbA1c: Delay DN
DCCT Research Group. New Engl J Med 329:977, 1993
116
Decline of GFR in DN
118
119
Chronic Kidney Disease:
A Silent Epidemic (Part 2)
Naima Ogletree, MSN, APRN, BC
Nephrology & Hypertension
Henry Ford Health System
Proteinuria Reduction
121
CKD: Albuminuria
Nontimed Urinary
Timed Urinary
Albumin Sample
Albumin Sample
Adjusted by
Unadjusted Urine Cr Overnight 24 Hr
(mg/g)
(g/ml)
(g/min) (mg/24 hr)
Normoalbuminuria
<20
Microalbuminuria 20–200
Macroalbuminuria
>200
<30
<20
<30
30–300
20–200
30–300
>300
>200
>300
G Remuzzi, et al. New Engl J Med. 2002; 346:1145–1150.
122
Proteinuria
Dual Significance
•Proteinuria results from injury to
glomerular circulation
 Increased proteinuria is associated
with progressive CKD
•In diabetes and hypertension,
proteinuria signifies injury to the
systemic circulation
 Proteinuria is associated with
increased CV risk
123
RAAS, Albuminuria and Atherosclerosis
Steno Hypothesis
American Journal of Kidney Diseases, Vol 47, No 6 (June), 2006: pp 927-946
124
CKD: Anti-Proteinuric Therapy
• Rationale for Intervention
 Microalbuminuria — independent CVD
risk factor
 In-hospital mortality  3-fold by
proteinuria (100 mg pro/g Cr)
 Proteinuria correlates with CKD
progression
 Proteinuria may worsen CKD
Adapted from multiple studies. HOPE subanalysis: JFE Mann, et al. J Am Soc Nephrol. 2003;
14:641–647. MARVAL: Circulation. 2002;106:672-678. RENAAL: N Engl J Med. 2001;345:861–
869. IDNT: N Engl J Med. 2001;345:851–860.
125
Albuminuria Decreases Survival
Survival (all-cause mortality)
Graded Effect
1.0
Normoalbuminuria
(n=191)
0.9
Microalbuminuria
(n=86)
0.8
0.7
Macroalbuminuria
(n=51)
0.6
0.5
0
1
2
3
P<0.01 normoalbuminuria vs microalbuminuria
P<0.001 normoalbuminuria vs macroalbuminuria
P<0.05 microalbuminuria vs macroalbuminuria
4
5
6
Years
Gall MA, et al. Diabetes. 1995;44:1303-1309.
www.hypertensiononline.org
Gall MA, et al. Diabetes 1995;44:1303-1309
Copyright ©1995, American Diabetes Association. Reprinted with permission.
126
UPC @ 6 Mo Predicts Kidney & CVD Events
RENAAL Substudy (losartan, no ACEI)
Hazard ratio (95 % C.I.)
ESRD
CV events
CHF
More Risk →
← Less Risk
0.2
0.4
0.6
0.8
1
1.2
Proteinuria (g)
RENAAL Study Group, 2002
127
BP, Proteinuria and CKD
• Reduction of protein and albuminuria
 Intermediate goals in slowing CKD
 Complementary
• Aggressive BP control is primary
consideration of “anti-proteinuria”
• Multi-drug regimens required
128
Renin-Angiotensin System Blockade
• Moderate to high doses of ACEIs / ARBs
have been associated with beneficial
effects on kidney disease progression in
controlled trials
• Where tested, ACEIs / ARBs have
generally similar effects on BP, urine
protein excretion, and slowing CKD
progression
Greatest efficacy in proteinuric disorders
129
How RAAS Blockade is Beneficial
Renal Disease
Renal Na Excretion
Hypertension
Excess Ang II
Efferent arteriolar
resistance
Diabetes
Obesity*
Afferent arteriolar
resistance
PGC
Glomerular
damage
Nephrons
Adapted from Hall JE et al. J Am Soc Nephrol. 1999;10:S258-S265.
A Chagnac, et al. Glomerular hemodynamics in severe obesity. Am J Physiol 2000;278;F817-F822.
130
ACEIs / ARBs
• Clinicians often avoid / withdraw
ACEIs / ARBs in CKD …
fearing hyperkalemia or ↑ SCr
• Tolerate …
 … up to 30% increases of SCr
 … [K] of 5.5–5.8 mEq/L
• Kidney dietitian, not Kayexelate
FF Hou, et al. NEJM, 2006.
131
Alternative to RAAS Blockers
• Non-dihydropyridine CCBs for those
who cannot tolerate anti-RAAS
agents, especially with proteinuria
 Diltiazem
 Verapamil
132
CKD: Anti-Proteinuric Therapy
• RAAS blockade
 ARBs preferred in type 2 diabetic
nephropathy
 ACEIs preferred in type 1 diabetic
nephropathy
• Quantitate proteinuria q1-2 mo
 Proteinuria reduction maximized by
Week 8 of tx
 Perform “spot” urine tests to assess
efficacy
From HOPE: JFE Mann, et al. J Am Soc Nephrol 2003; 14:641–647.
MARVAL. Author. Circulation 2002;106:672-678. RENAAL. BM Brenner, et al. N Engl J Med
2001;345:861–869. IDNT. EJ Lewis, et al. N Engl J Med;345:851–860.
133
RENAAL: Combined CCB and ARB Reduce
Progression to Diabetic Nephropathy
NORMAL
Paff
PGC
REA
RAA
CCB
Paff
Peff
NORMAL
PGC
Peff
ACEI (type 1 DM)
ARB (type 2 DM)
Adapted from RENAAL Study. BM Brenner, et al. N Engl J Med. 2001;345:861–869.
RAA, afferent arteriolar resistance. REA, efferent arteriolar resistance.
134
IRMA 2: ARB Prevents Transition
from Micro- to Macroalbuminuria
Incidence of Diabetic
Nephropathy (%)
20
Control (n=201)*
Irbesartan 150 mg/d (n=195)*
Irbesartan 300 mg/d (n=194)*
15
RRR=39%
P=.08
10
RRR=70%
P<.001
5
0
0
3
6
12
Followup (mo)
18
22
24
H-H Parving, et al. New Engl J Med. 2001;345:870–878.
136
IRMA 2: ARB Normalizes Albumin
Excretion Rate
45
P=.006
Normal UAR (%)
40
34
35
30
25
21
24
20
15
10
5
0
Control†
(n=201)
†P
<0.05
150 mg/d†
300 mg/d†
(n=195)
(n=194)
Irbesartan
H-H Parving, et al. New Engl J Med. 2001;870–878.
137
Effect of AngII Receptor Blockade
in Type 2 Diabetic Nephropathy
Patients:
Treatment arms:
Target BP:
Adjunctive therapy:
Primary outcome:
Secondary outcomes
included:
Mean Follow-up:
‡
IDNT†
RENAAL
1,715 HTN patients with type 2
diabetes and nephropathy
irbesartan, amlodipine, placebo
135/85 mm Hg
Permitted except ARBs,
ACE inhibitors, or CCBs
1,513 HTN patients with type 2
diabetes and nephropathy
losartan, placebo
140/90 mm Hg
Permitted including CCBs;
except ARBs or ACE inhibitors
Composite of doubling of SCr,
ESRD, or death
CV events
Composite of doubling of SCr,
ESRD, or death
CV events
2.6 years
3.4 years
SCr, serum creatinine; ESRD, end-stage renal disease.
† Lewis EJ et al. N Engl J Med. 2001;345:851-860.
‡ Brenner BM et al. N Engl J Med. 2001;345:861-869.
BM Brenner, et al. N Engl J Med 2001;345:861–869.
138
Irbesartan Diabetic Nephropathy Trial
70
Irbesartan (n=579)
RRR=23%
P=.006
RRR=20%
Amlodipine (n=565)
P=.02
P=NS
Control (n=568)
60
Patients (%)
50
40
30
20
10
0
0
6
12
18
36
30
24
Follow-up (mo)
EJ Lewis, et al. N Engl J Med. 2001;345:851–860.
42
48
54
139
Reduction in Endpoints in Non-Insulin
Dependent DM with the Angiotensin II
Antagonist Losartan
Intention-to-treat analysis
50
Risk Reduction: 16%
p=0.024
Placebo
% with event
40
Losartan
30
20
10
0
0
12
24
36
48
Months
BM Brenner, et al. N Engl J Med 2001;345:861–869.
140
Diabetes and RAAS Blockade
Type 2 DM
• Brenner et al. (losartan, RENAAL)
(N=1513)
• Lewis et al. (irbesartan, IDNT)
(N=1715)
• ARBs reduced proteinuria (~35%)
 reduce rate of GFR decline
 later onset of ESRD compared to placebo
• Mean delay of ESRD by ~2.3 yr
141
Lipid Control
142
Guideline: Lipids in CKD 1–4
1.1. All adults and adolescents with CKD should be
evaluated for dyslipidemias. (B)
1.2. For adults and adolescents with CKD, the
assessment of dyslipidemias should include a
complete fasting lipid profile with total
cholesterol, LDL, HDL, and triglycerides. (B)
1.3. For adults and adolescents with Stage 5 CKD,
dyslipidemias should be evaluated upon
presentation (when the pt is stable), at 2–3 MO
after a change in treatment or other conditions
known to cause dyslipidemias; and at least
annually thereafter. (B)
Dyslipidemia & CKD
Treatment Protocol
LDL
TG
NON-HDL-C
4
Lifestyle Modification … Always
144
Dyslipidemia & CKD
Treatment Protocol
Lifestyle Modification … Always
145
CKD: Lipid Therapy
• Rationale for Intervention
 CKD progresses faster in dyslipidemia
 Physicians’ Health Study (1982–1996)
• N=4,483 initially healthy males
• 14-Yr followup
o Baseline SCr <1.5 mg/dL
o HDL >40 mg/dL: 50%  risk of reduced GFR
o Non-HDL-C >196 mg/dL: 100%  risk of
reduced GFR
T Kurth, et al. J Am Soc Nephrol 2003;14:2084–2091.
148
CKD: Lipid Targets
Parameter
NCEP ATP III
K/DOQI Revision
LDL-C (mg/dL)
<130
<100
HDL-C (mg/dL)
>40
>40
<150
<150
Normal lipids (HD)
20.2%
38.9%
Normal lipids (PD)
15.1
—
TG (mg/dL)
Kidney/Dialysis Outcomes Initiative Clinical Practice Guidelines for Managing
Dyslipidemias in Chronic Kidney Disease. Am J Kidney Dis 2003:41(Suppl 3):S1–S91.
149
CKD: Dyslipidemia Therapy
• HMG-CoA synthetase inhibitors
• Fibric acid derivatives
 Use with caution
 Gemfibrozil preferred
• Cholesterol absorption inhibitor
 Ezitimibe (Zetia™) — statin-sparing
 No controlled trials in CKD
Kidney/Dialysis Outcomes Quality Initiative Clinical Practice Guidelines for Managing
Dyslipidemias in Chronic Kidney Disease. Am J Kidney Dis. 2003:41(Suppl 3):S1–S91.
150
Anemia of CKD
152
CKD: Anemia Induces LVH
Excerpt: H Hampl, L Henning and E Riedel. Dialysis Times 2003;9(5):1–6
A Mohanran and AS Kliger presentations at NKF Meeting 2003
154
NKF KDOQI Guideline & CPR 2.1:
Hb range
• Moderately strong recommendation
2.1.1 Lower limit of Hb
In pts with CKD, the Hb
should be > 11
g/dL
• 2.1.2 Upper limit of Hb
In the opinion of the Work Group,
there is insufficient evidence to
recommend routinely maintaining Hb
levels > 13 g/dL in ESA treated pts.
156
CKD: Anemia Therapy
• Rationale for Intervention
 Anemia worsens with CKD progression
• Tx regresses LVH/LVMI
• Tx prevents CHF and hospitalization
• Tx slows CKD progression?
 QOL improved by  Hb
• Cognition
• Sexual function
• Exercise tolerance
Excerpt: H Hampl, et al. Dialysis Times 2003;9(5):1–6. Presentations: A Mohanran
and AS Kliger. National Kidney Foundation Annual Meeting, 2003.
157
CKD: Anemia  as GFR 
15
Mean Hb* (g/dL)
14
13
12
11
10
9
8
7
6
5
n=59
n=29
n=18
n=18
n=34
n=18
 91
90–40
39–30
29–20
19–10
 10
GFR (mL/min/1.73 m2)
Adapted from Radtke, et al. Blood. 1979;54:877–884 (original study used Hct).
158
RBC Production Response in CKD
6X
RBC Production
(mL/Day)
5X
Normal
4X
3X
CKD
2X
1X
0
0.1
1.0
10
10
2
10
3
10
4
EPO Concentration (mU/mL)
159
EPO Response Blunted as CKD Progresses
Hemoglobin
EPO level (mU/mL)
(g/dL)
15
Expected
EPO levels
14
13
12
11
10
9
8
7
N=
6
59
29
18
18
34
18
40-25
25-15
15-10
<10
5
100-70 70-40
Percent of Normal Kidney Function
Radtke HW. et al Blood 1979;54:877; Erslev AJ. N Engl J Med 1991;324:1339
160
Anemia: A Risk Multiplier
8.0
7.3
7.0
6.0
6.3
6.0
4.6
5.0
3.6
4.0
3.0
2.0
1.0
1.5
2.0
2.0
2.4
2.4
3.7
3.7
4.7
4.0
2.9
1.0
D
N
on
e
M
A
on
ne
ly
m
ia
on
ly
C
K
D
D
M
on
/C
D
ly
M
K
D
/A
o
ne
m nly
ia
D
M
on
/C
ly
C
K
H
D
F
/A
on
ne
ly
m
ia
D
on
M
C
ly
/
C
K
H
D
F
/A
on
ne
C
ly
H
m
F/
ia
D
A
M
on
ne
/C
ly
m
H
F/
ia
A
ne on
ly
m
C
i
C
a
H
H
on
F/
F
C
/
ly
C
K
K
D
D
/A
on
ne
D
ly
M
m
/C
ia
D
H
M
on
F/
/C
ly
C
H
K
F/
D
C
on
K
D
ly
/A
ne
m
ia
0.0
Source: Medicare sample (5%), followup from 1996 to 1997 of enrollees aged >65 y.o.,
adjusted for age, gender and race.
QoL Improves with Higher Hb
• Cognitive function
• Exercise capacity
• Energy/activity
• Functional ability
• Sleep and eating
behavior
• Health Status
• Satisfaction with
health
• Well-being
• Sex Life
• Psychological effect
• Happiness
• Satisfaction
162
How Can We Reach Hb Target?
• Efficient erythropoesis requires both iron and
erythropoetin.
• Use of maintenance iron improves patients’
response to EPO therapy, replaces continuous
iron losses, and maintains patients’ target
Hb/HCT ranges.
• IV iron improves iron and hematologic
parameters with health benefits that outweigh
the potential adverse effects.
Besarab, A.
Clin J Am Soc Nephrol 1:S1-S3, 2006
Operationalizing the CKD Clinic
163
IV Iron May Have an Independent
Erythropoietic Effect in HD
*
11
Hgb, g/dL
10
Baseline
*
12 mo
26 mo
9
8
7
6
5
IV Iron
Oral Iron
No Iron
39 new HD pts (no EPO therapy) with baseline iron deficiency by
bone marrow aspiration.
*P <0.01 vs baseline.
Fudin et al. Nephron. 1998;79:299–305.
164
More Rapid Hgb Response
With EPO + IV Iron
1.0
• Charts of 58 CKD pts were reviewed
0.9
0.8
% Not Reaching
Primary
Endpoint*
0.7
IV Iron Alone (n=28)
0.6
EPO + IV Iron (n=30)
0.5
0.4
0.3
0.2
0.1
P=.037
0.0
0
50
100
150
200
250
300
Days
*Defined as 0.5-g/dL increase in Hgb.
Panesar et al. Am J Kidney Dis. 2002;40:924-931.
165
Available Oral Iron Preparations
Strength
Elemental Fe
(mg/tablet) (mg/tablet)
No. Tablets to
Supply 200 mg
Elemental Fe
Ferrous
sulfate
325
65
3
Ferrous
gluconate
325
38
5
Ferrous
fumarate
200
66
3
Iron polysaccharide
150
150
2
166
Currently Available
Erythropoietic Agents
•First generation erythropoietic agents
─
─
─
•
Epoetin alfa (Amgen [Epogen]
®,
J&J [Procrit]®)
Epoetin beta (Roche)
Epoetin omega (South America)
Epoetin delta (in clinical trials, humanized using
immortalized
•Second generation epoetin
─ Darbepoetin alfa (Amgen, Aranesp®)
•Other erythropoietic agents in clinical trials
─ PEG-epoetin beta (CERA Roche)
─ Hematide (totally synthetic peptide)
─ Fibrogen product. HIF1-alpha inhibitor
167
CKD: Anemia Therapy
• Begin tx at Hb <11 g/dL (Hct 33%)
• Steps (by Nephrology CKD Clinic)
1. Replete iron stores
•
•
Oral
Iron
Iron
Iron
iron salts
dextran (INFeD) or
gluconate (Ferrlecit) or
sucrose (Venofer)
2. Use erythropoietic agent
• Epoetin-a (Procrit) or
• Darbepoetin (Aranesp)
J Yee, A Besarab. Am J Kidney Dis 2002;40:1111–1121
168
CKD: Anemia Therapy
• Targets
 Hb >11 g/dL (Hct 33%)
 TSAT >20%; Ferritin >100 ng/mL
• EPO level
 Does not predict marrow response
• Two-thirds of levels in “normal range”
• Do not obtain EPO levels
• R/O blood loss and/or iron deficiency
A Besarab, J Yee. J Am Soc Nephrol 1999;10:2029–2043
AR Nissenson. Am J Kidney Dis 2001;38:1390–1397
169
Chronic Kidney Disease—Mineral
and Bone Disorder
170
Position Statement from KDIGO
(Kidney Disease Improving Global Outcomes)
Definition of CKD-MBD
A systemic disorder of mineral and bone
metabolism due to CKD manifested by either
one or a combination of the following:
• Abnormalities of calcium, phosphorus, PTH, or
vitamin D metabolism
• Abnormalities in bone turnover,
mineralization, volume, linear growth, or
strength
• Vascular or other soft tissue calcification
Definition, evaluation, and classification of renal osteodystrophy. KI, April 2006
171
Position Statement from KDIGO
(Kidney Disease Improving Global Outcomes)
Definition of Renal Osteodystrophy
Renal osteodystrophy is an alteration of bone
morphology in pts with CKD.
It is one measure of the skeletal component
of the systemic disorder of CKD-MBD that is
quantifiable by histomorphometry of bone
biopsy.
Definition, evaluation, and classification of renal osteodystrophy. KI, April 2006
172
CKD: Metabolic Bone Disease
• Consequence of  renal mass
  Vitamin D3
 P
  Ca2+
 Metabolic acidosis
• Increased protein catabolism
• Increased bone lysis / loss
Draft: Kidney/Dialysis Outcomes Initiative Clinical Practice Guidelines for Bone
Metabolism and Disease. National Kidney Foundation Task Force, 2003
173
CKD: Metabolic Bone Disease
• Definition — any / all metabolic
bone disorders associated with CKD
 2° hyperparathyroidism
 Osteoporosis
 Osteomalacia
 Adynamic bone disease
 Mixtures of above
KA Hruska, SL Teitelbaum. New Engl J Med. 1995;333(3):166-174.
DJ Sherrard, et al. Kidney Int. 1993;43(2):436–442.
174
CKD: Metabolic Bone Disease
• Rationale for Intervention
 Multiple aberrations of Ca/P/PTH and
bone metabolism accompany GFR
decline.
 Hyperphosphatemia is an independent
CV risk factor in ESRD (presumed in nonESRD CKD).
 ESRD pts develop CV calcification (by
EBCT) from  Ca × P product.
WG Goodman, et al. New Engl J Med. 2000;342(20):1478–1483.
175
CKD: Pathophysiology of 2° HPT
 PTH
 PTH
 Ca2+
Bone Disease
 Vit D3
P
Systemic Toxicity
CKD
176
Progression of PTH Gland
Hyperplasia in CKD
Decline in
receptor density
of VDR, CaR
Cells with lower density of VDR
proliferate vigorously to form
several monoclonal nodules
Monoclonal nodules
Normal
Diffuse
Early
nodular
Nodular
hyperplasia
Single nodule
CKD Progression
VDR = vitamin D receptor; CaR = Ca-Sensing receptor.
Adapted from Murayama A et al. Endocrinology. 1999;140:2224-2231. Satomura K et al. Kidney Int. 1988;34:712–716
177
CKD: Renal Osteodystrophy
— Ca / P / PTH Axis
Parameter
Alteration
GFR
PTH

Increased
40 -70
Pi

Increased
20 -50
CalcitriolD3
Vitamin

Decreased
<40
Variable
—
Bone histology
KG Koenig, et al. Kidney Int. 1991;41:161–165.
178
CKD: ROD PTH Target
150
100
Low bone turnover
Adynamic bone disease
K/DOQI
PTH
Target
(pg/mL)
300
500
High bone turnover
Bone pain
Cardiovascular disease
Cognitive impairment
179
CKD: ROD Ca Target
8.4
K/DOQI
Target
Ca
9.5
(mg/dL)
10.2
7.5
Stimulus for PTH secretion
Stimulus for PT gland enlargement
Inadequate skeletal mineralization
Vascular/soft tissue
calcification
Hypertension
180
CKD: ROD P Target
3.5
K/DOQI
Target
P
5.5
(mg/dL)
2.5
Malnutrition
Inadequate bone mineralization
6.5
Vascular/soft tissue calcification
Cardiovascular disease
Higher mortality risk
181
CKD: Renal Osteodystrophy
• Targets
 Ca
8.4–9.5 mg/dL
 P
2.7–5.5 mg/dL
 Ca × P
<55 mg2/dL2
 HCO3
22–26 mEq/dL
 PTH
<2–3× ULN (100–150 pg/mL)
Draft: Kidney/Dialysis Outcomes Initiative Clinical Practice Guidelines for Bone
Metabolism and Disease. National Kidney Foundation Task Force, 2003
182
CKD: Renal Osteodystrophy
—  P  Relative Risk of Mortality
Relative Mortality Risk
2.0
1.39**
1.5
1.18*
1
1
1.02
1.0
0.5
1.1-4.5
4.6-5.5
5.6-6.5
6.6-7.8 7.9-16.9
Serum Phosphorus Quintile (mg/dL)
GA Block, et al. Am J Kidney Dis 1998;31:607–617.
183
Mortality Risk in ESRD
by Serum P and Ca Levels
N = 40,538
RR of Death*
2.2
2.0
2.0
1.8
1.8
1.6
1.6
1.4
1.4
1.2
1.2
1.0
1.0
0.8
0.8
0.0
0.6
<3
3-4
4-5 5-6 6-7 7-8 8-9
>9
Serum P (mg/dL)
0.0
<8.0
8.08.5
8.59.0
9.09.5
9.510.0
10.0- 10.510.5 11.0
>11.0
Serum Ca (mg/dL)
RR = relative risk
*Not adjusted for active vitamin D intake
Block et al. J Am Soc Nephrol. 2004;15:2208-2218.
184
Prevalence of Calcitriol Deficiency and
Anemia in pts With CKD by eGFR
Design
100
• N = 80 CDK
Calcitriol Deficiency
• Anemia defined as Hb
<11 g/dL or treatment
with ESA
Anemia
Results
• Prevalence of calcitriol
deficiency was greater
than prevalence of
anemia at all stages of
CKD
Subjects (%)
• Calcitriol deficiency
defined as calcitriol
<30 pg/mL
80
60
40
20
0
>60
45-60
30-45
<30
eGFR (mL/min/1.73 m2)
Gutierrez et al. J Am Soc Nephrol 2005;16:2205-2215.
185
SHPT Occurs Early in CKD
CKD Stage 1
Stage 2
Stage 3
Stage 4
5.6 million
5.7 million
7.4 million
300,000
400
40
300
30
25
200
20
10
target
target
iPTH (pg/mL)
1,25(OH)2D3
Calcitriol (pg/mL)
N=150
100
70
0
105
95
Martinez et al. NDT 1996;11:22-28.
85
75
65
55
45
eGFR (mL/min/1.73 m2)
35
25
15
186
CKD-Mineral & Bone Disorder
Ca/P/PTH Progression in CKD
200
6
PTH
*
Ionized Calcium
150
5
125
*
100
*
mg/dL
PTH, pg/mL
175
4
75
Phosphorus
50
3
25
0
2
CrCl mL/m
CrCl mL/m
*P < 0.05,compared to CrCl > 100 and CrCl 50-59, N = 157
Martinez I, et al. Am J Kidney Dis. 1997;29:496-502.
187
Recommendations for Early Monitoring
of PTH, Ca, and P Metabolism in CKD
CKD
Stage
3
GFR
Range
Measure
PTH
Measure
Ca & P
30–59
12 MO
12 MO
4
15–29
3 MO
3 MO
5
<15 or ESRD
3 MO
1 MO
GFR in mL/min/1.73 m2
KDOQI Guidelines for Bone Metabolism and Disease. Am J Kidney Dis. 2003;42(4 suppl 3):S1-S201.
188
Vitamin D in CKD Stages 3 and 4
Stages 3 and 4:
Level
Measure serum 25(OH) D in pts with  PTH.
If normal, repeat q12 mo.
Normal 25(OH)D 30 ng/mL
Insufficiency <25
Deficiency <15 ng/mL
Treatment with Vitamin D2
(Ergocalciferol, 50,000 IU capsules)
<5 ng/mL
50,000 IU/wk x 12, then q MO x 6
5–15 ng/mL
50,000 IU/wk x 4, then q MO x 6
16–29
ng/mL
50,000 IU/MO x 6
NKF. Am J Kidney Dis. 2003;42(4 suppl 3):S1-S201.
189
CKD: Metabolic Bone Disease Tx
• Vascular calcification at any site


Avoid Ca-containing P-binders
Use sevelamer (not confined to ESRD)
• Ca >10.2 mg/dL, stop calcitriol


Switch to non-Ca-containing P-binders (sevelamer)
Limit elemental Ca in Ca-based binders to 1500
mg/d or sum of total dietary Ca plus elemental Ca
to 2000 mg/d
• P >5.5 mg/dL



Switch to non-Ca-containing P-binders (sevelamer)
Restrict P to 0.8–1.0 g/d if P >5.5 mg/dL
Restrict P to 0.8–1.0 g/d if PTH >50 pg/mL
Draft: Kidney/Dialysis Outcomes Initiative Clinical Practice Guidelines for Bone
Metabolism and Disease. National Kidney Foundation Task Force, 2003
190
High-Turnover Bone Disease Can
Result in Soft-Tissue Calcification
Phosphorus
PTH
Calcium
Magnesium
Deposition
Into Tissues
Calcification
191
Low-Turnover Bone Disease Can Result in
Soft-Tissue Calcification
Phosphorus
PTH
Calcium
Magnesium
Deposition
Into Tissues
Calcification
192
CKD: Renal Osteodystrophy Tx
• Ca-based P-binders

Ca acetate (Calphron™, PhosLo™)
•

667 mg (elemental Ca); 1 capsule tid with meals
Ca carbonate (Tums™)
•
500 mg (elemental Ca): 1 tab tid with meals

Ca-based P-binders in CKD Stages 3 and 4 permitted

Avoid concurrent Ca-based P-binder and iron salt
ingestion

Avoid concurrent Ca-based P-binder and
levothyroxine ingestion
Draft: Kidney/Dialysis Outcomes Initiative Clinical Practice Guidelines for Bone
Metabolism and Disease. National Kidney Foundation Task Force, 2003
193
CKD: Renal Osteodystrophy Tx
• Non-Ca-based binders
 Avoid aluminum-based gels
 Sevelamer hydrochloride (Renagel™)
• Use in CKD Stages 3 and 4
o 800 mg capsules: 1–2 tid with meals
o Only FDA-approved for ESRD
• Alone or with Ca-based P-binders
Draft: Kidney/Dialysis Outcomes Initiative Clinical Practice Guidelines for Bone
Metabolism and Disease. National Kidney Foundation Task Force, 2003
194
CKD: Metabolic Acidosis
• The serum bicarbonate reflects the degree
or severity of systemic acidosis. This
parameter should be at 22 meq/L or
greater, to offset acidosis-driven bone lysis.
• Bicarbonate therapy

NaHCO3 dose: 0.5–1.0 mEq/kg bw/d
• 3.87 mEq per 325 mg tablet
• 7.73 mEq per 650 mg tablet
• Usual CKD dose 1300 mg TID
FC Husted, et al. J Clin Invest. 1975;56(2):414–419.
195
Acidosis Aggravates Renal
Osteodystrophy
196
Acidosis Treatment
• May occur earlier in diabetic CKD,
compared to non-diabetic CKD
 Type IV RTA
• Treatment same in diabetic and nondiabetic CKD
 HCO3 > 22 mEq/L
 NaHCO3 tablets (0.5–1.0 mEq/kg/day)
Verify acidemia with ABG
197
Nutritional Assessment
198
Nutrition Assessment
• Dietician (RD) — integral part of CKD
management.
Consultation at any CKD stage.
• Utilize RD within 2 wk of initial consultation
for dietary assessment and
recommendations.
• RD will educate pts on food preparation
techniques → increasing compliance with
dietary restrictions.
199
Rationale for RD consult
• Malnutrition evolves during the
progression of CKD
• Hypoalbuminemia and vitamin
deficiencies are common
• Diet high in biological value must be
maintained, while restricting Na, P, K
200
Food Sources
• Na++ — usually all processed foods (hot dogs,
bologna, soups) are high in Na. Be wary of
foods that are labeled “low in sodium”. The RD
will need to determine ‘how low is low’.
• K+ — chief sources are fruits and vegetables
and anything that grows below or sits in the
ground. Highly colored fruits (i.e.,
watermelon), deep green vegetables, even
dried fruits.
• P04 — all high P foods are also in high K foods,
unless phosphoric acid is added. Found in dairy
products (except butter). Foods prepared with
skim milk (i.e., cake mix, biscuits), nuts, dried
peas, baked beans, legumes and colas.
201
Intervention
• Caloric restriction:
 25 cal/kg of SBW to lose wt
 30 cal/kg of SBW to maintain wt
 35–40 cal/kg of SBW to gain wt
• Fluid restriction:
 implement only if Na<132 mEq/L and pt
is compliant with low Na diet.
 may be temporary
202
CKD: Nutrition
• Rationale for Intervention
 amino acid loads induce glomerular
hyperfiltration
 protein restriction in small studies
retards CKD progression, but not in
largest RCT, MDRD study
 obesity (BMI >38 kg/m2) — associated
with glomerular hyperfiltration
S Klahr, et al. N Engl J Med 1994;330:877–884.
EL Knight, et al. Ann Intern Med 2003;138:460–467.
203
CKD: Nutrition —  Protein Intake
Associated with  Kidney Function
• Nurses’ Health Study (n=1135
females); 11-year followup
 Median protein intake, 92.3 g/d
 Each 10-g  in non-dairy protein
intake  CCr by 1.21 mL/min
 Highest quintile  CCr by 4.77 mL/min
S Klahr, et al. for th MDRD Study Group. N Engl J Med. 1994;330:877–884
EL Knight, et al. Ann Intern Med 2003;138:460–467.
204
CKD: Nutrition Therapy
• Consult Renal Dietitian at CKD Stage 3
• Protein restrict @ GFR <25
mL/min/1.73 m2
 High biologic protein: 0.6–0.75 g/kg bw
 Initiate dialysis if …
• GFR <15–20 with energy malnutrition from low
protein intake
• 6% wt loss or <90% of IBW in <6 mo
Kidney/Dialysis Quality Outcomes Initiative Clinical Practice Guidelines for Managing
Dyslipidemias in Chronic Kidney Disease. Am J Kidney Dis 2003:41(Suppl 3):S1–S91.
205
Dietary P Restriction to Control
SHPT in CKD
• Commentary:
“In summary, the available data and the OPINION of the
Work Group support the proposal that dietary phosphate
restriction should be initiated when blood PTH levels
begin to rise (Stage 2) and/or when serum phosphorus
levels are elevated at any stage of CKD.” p S65
• KDOQI Guideline 4. Restriction of Dietary Phosphorus in pts
with CKD
4.1 Dietary phosphorus should be restricted to
800–1000 mg/day when the serum phosphorus levels
are elevated (4.6 mg/dL) at CKD Stages 3 and 4
(OPINION; p S63)
NKF. Am J Kidney Dis. 2003;42(4 suppl 3):S1-S201.
206
Vaccinations
207
Vaccinations
• CKD pts immunocompromised
• Despite immunodeficiency, CKD pt
immunized less frequently against flu
and S pneumoniae than general
medical pts
208
Vaccinations: Recommendations
• Annual influenza A/B
• 23-valent polysaccharide
pneumoccocal (Pneumovax, PPV23)
Q6 years
• HBV vax — give at any CKD stage.
Immunization series should be
completed by stage 4 since “late”
stage 5 vax induces lower Ab titers
209
Influenza Vax rates Below National Target
(Healthy People 2000)
80%
70%
60%
50%
60%
60%
49%
39%
30%
40%
30%
20%
10%
0%
HD
PD
_______________
Dialysis pts
Whites
Non Whites
2000
__________________________
General Population
Gilbertson et al, Kidney Int 2003; 63:738-743; MMWR 2001, 50:532-37
210
Odds of Hospitalization & Death are
Reduced In Vaccinated HD pts
1.3
1.2
1.1
1
0.9
0.8
0.7
0.6
Any
Cause Influenza
_________________
Hospitalization
Any
Cause
Cardiac
Infection
__________________________
Death
Gilbertson et al, Kidney Int 2003; 63:738-743
211
Evaluate Progression of CKD
212
Strategies to Improve Vascular
Access – Education
NKF-K/DOQI Guidelines
• Education when SCr >3 mg/dl
• Vascular access is necessary to access
blood circulation. Refers to fistulas,
grafts, and catheters.
Vascular Access
• Preserve arm veins suitable for
placement of vascular access,
regardless of arm dominance.
• Arm veins, especially cephalic veins
of the non-dominant arm, should not
be used for venipuncture or iv
catheters.
214
Vascular Access
• Dorsum of the hand should be used
for iv lines. When venipuncture of the
arm veins is necessary, sites should
be rotated.
• Avoid subclavian vein cannulation —
increases risk of central vein stenosis
215
DIALYSIS Arteriovenous Fistula
• Surgically connect endogenous artery
to endogenous vein (no Gortex, AVG)
• Safest and longest half-life of all
accesses
• Least expen$ive
216
AV Fistula
Strategies to Improve Vascular Access –
Timing of Access Placement
NKF-K/DOQI Guidelines
• Refer to surgery for primary AVF
construction if …
 GFR <25 mL/min
 SCr >4 mg/dL
 within 1 yr of anticipated dialysis
• AVF maturation time
 Okay: >1 month
 Ideal: 3–4 mo, prior to cannulation
Fistula: Disadvantages
• “Bulge” — unattractive
• Never matures
 Conversion to AVG, possible
 Temporary HD catheter may be req’d
219
Vascular Access: AVG
• Construction timing — 3 to 6 weeks
before anticipated need
• When — AVG reserved for pts who
are not candidates for an AVF or
where AVF failed
• Clot more frequently than AVFs
• Overall half-life 2.5 yr
220
AV Grafts
221
Catheters
• Cannulation of large central vein
• Temporary in most cases
• Lower Qb, i.e., less efficient HD
• Requires meticulous care
 Much higher infection/mortality rates
 ~50% infection rate at 6 mo
222
Catheter
Locations
223
Majority of Pts Start RRT Without
A Permanent Vascular Access
Permanent Access Placed or Attempted Before Start of RRT ?
Yes
43.9%
Unsure
7.9%
No
48.2%
Held et al, AJKD 1996, 28 (Suppl. 2):58-78, USRDS DMMS I (1,997 pts incident in 1993)
224
Vascular Access Used for the
First Chronic Hemodialysis
US
70%
60%
50%
40%
30%
20%
10%
0%
Europe
66%
60%
31%
24%
15%
2%
AV Fistula
AV Graft
Catheter
Pisoni et al, Kidney Int 61:305-16, 2002. Random sample of 2,179 US and 875
European pts who began HD between 7/1996-10/2000 (US) and 7/1998-10/2000
(Europe) — DOPPS.
225
Risk of Infectious Mortality is
Increased with Temporary Access
Diabetics
Non-Diabetics
3.0
2.47
RR of ID Mortality
2.5
2.30
1.83
2.0
1.5
1.27
1.00
1.00
1.0
0.5
0.0
Ref.
AVF
P <0.02 P <0.06
AVG
CVC
Ref.
AVF
P <0.33 P <0.04
AVG
CVC
Dhingra et al, Kidney Int 60:1443-51, 2001. Adjusted for age, gender, race, BMI, smoking,
education level, ability to ambulate, and history of PVD, CHD, CAD and cancer.
226
Pts With Temporary Access Have
Higher Rate of Hospital Utilization
Number of hospital days
per patient-yr at risk
Temporary
50
Permanent
41.9
40
30
20
22.7
17.6
14.6
13.7
12.1
10
0
Overall
First 3 months
Arora et al, J Am Soc Nephrol, 11:740-7476
After 3 months
227
Vascular Access Survival and
Revisions
AVFistula
Transp Vein Fistula
AVGraft
aRR of Outcome
2.5
1.91
2.0
1.41
1.5
1.00
1.13
1.32
1.00
1.0
0.5
NS
<0.001
<0.05 <0.001
0.0
Primary Patency
Revision
Gibson et al, J Vasc Surg 2001;34:694-700. Adjusted for age, gender, race, previous
access
228
% of pts with fistula ascurrent access
AVF (USRDS)
50
50%
(2010
target)
40
30
28.4%
(2000
actual)
20
10
0
illi
illi
lla
lla
1991 1992 1993 1994 1995 1996 1997 1998 1999 2000
New patients
using AVfistulas
Prevalent hemodialysis pts from 2001 CPM data, year represents year in
which dialysis was initiated; current access from 2001 CPM survey data;
includes only pts for whom an access type is known.
229
Fistula First Initiative
• A national initiative to expand the
number of pts with AVFs, as opposed
to catheters or AVGs.
• To date, the initiative has surpassed
its target of 40% prevalent pts
• Year 2010: goal is 50% of all new pts
on HD. 66% of continued pts will use
fistulas.
230
Download information
• Updated editions of
Chronic Kidney Disease (CKD): Clinical
Practice Recommendations For Primary Care
Physicians and Healthcare Providers —
A Collaborative Approach (Ed 5.0)
can be downloaded from:
Ghsrenal.Com/CKD/Hfhs_CKD_Guidelines_v5.0.pdf
231
232