Chronic Kidney Disease
Definition, Early Intervention &
Measurement
Andrea Easom Ma, MNSc, APN, BC. CNN
University of Arkansas for Medical Sciences
Instructor, College of Medicine, Nephrology Division
Educational Objectives
• Define chronic kidney disease (CKD)
• Identify risk factors for progression and comorbid conditions
• Discuss how early intervention improves
outcomes during CKD progression
• Review measurements of kidney disease
Patients Who Are Aware of
Weak or Failing Kidneys* (%)
Awareness of Early-Stage CKD Is Low
in the US Population
20
18.6
17.9
15
10
5.5
5
0
Albuminuria:
eGFR:
3.9
1.6
1.1
<30
30+
90+
<30
2.9
2.4
30+
60-89
<30
30+ Sex: F
30-59
M
30-59
*Proportion of patients who were told they had weak or failing kidneys, eGFR (mL/min/1.73 m2).
Coresh et al. J Am Soc Nephrol. 2005:16:180-188.
© 2005 The Johns Hopkins University School of Medicine.
Definition of
Chronic Kidney Disease
AJKD 2002: 39(2)
Stages of
Chronic Kidney Disease
AJKD 2002: 39(2)
Definition and Stages of
Chronic Kidney Disease
AJKD 2002: 39(2)
Stages in Progression of CKD and
Therapeutic Strategies
AJKD 2002: 39(2)
Risk Factors for
Adverse Outcomes of CKD
AJKD 2002: 39(2)
Potential Risk Factors for
Susceptibility to and
Initiation of CKD
AJKD 2002: 39(2)
AJKD 2002: 39(2)
Why Estimate GFR From SCr, Instead
of Using SCr for Kidney Function?
Age
Gend
er
Race
eGFR
(mg/dL)
(mL/min/1.73
m2)
CKD
Stage
SCr
20
M
B*
1.3
91
1
20
M
W†
1.3
75
2
55
M
W
1.3
61
2
20
F
W
1.3
56
3
55
F
B
1.3
55
3
50
F
W
1.3
46
3
*B = black; †W = all ethnic groups other than black.
GFR calculator available at: www.kidney.org/index.cfm?index=professionals. Accessed 3/28/05.
Stages of CKD:
A Clinical Action Plan
AJKD 2002: 39(2)
Evaluation of Proteinuria in
Patients
Not Known to Have Kidney Disease
AJKD 2002: 39(2)
Diabetes
The Leading Cause of Kidney
Failure
Increased Mortality in Patients With Diabetes
and CKD: 2-Year Clinical Outcomes
100
No Events
ESRD, CKD Stage 5
Death
Patients (%)
80
60
61.6
67.6
84.0
40
6.1
2.9
20
0.3
29.5
32.3
- DM,
+CKD
+ DM,
+ CKD
15.7
0
+ DM,
- CKD
Medical Cohort
CKD identified as ICD-9-CM diagnosis code, includes CKD from diabetes, hypertension,
obstructive uropathy, and other diagnosis codes reported on USRDS ESRD registration forms.
DM = diabetes mellitus; ESRD = end-stage renal disease; ICD-9-CM = International Statistical
Classification of Diseases, 9th Revision, Clinical Modification.
Collins et al. Kidney Int. 2003;64(suppl 87):S24-S31.
© 2005 The Johns Hopkins University School of Medicine.
Advanced Kidney Outcomes by Year 8
of EDIC Reduced by Intensive Treatment
Intensive
Conventional
(n = 676)
(n = 673)
Creatinine
>2 mg/dL
5* (0.7%)
19 (2.8%)
Dialysis or
Transplant
4 (0.6%)
7 (1.0%)
Outcome
EDIC = Epidemiology of Diabetes Interventions and Complications.
*P = 0.004.
Writing team for the DCCT/EDIC Research Group. JAMA. 2003;290:2159-2167.
© 2005 The Johns Hopkins University School of Medicine.
Proteinuria Predicts Stroke and CHD
Events in Patients With Type 2
Diabetes
Prot <150 mg/L
Prot 150-300 mg/L
40
1.0
P<0.001
0.9
Incidence (%)
Survival Curves for
CV Mortality
Prot >300 mg/L
0.8
0.7
0.6
Overall: P<0.001
0.5
30
20
10
0
0
0
20
40
60
80
100
Stroke
Follow-Up (mo)
CHD
Events
CHD = coronary heart disease; Prot = urinary protein excretion; CV = cardiovascular.
Miettinen et al. Stroke. 1996;27:2033-2039.
© 2005 The Johns Hopkins University School of Medicine.
Evidence for Effects of Good Glycemic
Control on Complications, Including
Nephropathy
Trial
DCCT
A1C: (9 
7%)
N = 1441
Kumamot
o
(9  7%)
N = 110
UKPDS
(8  7%)
N = 5102
Retinopathy
 76%
 69%
 17-21%
Nephropathy
 54%
 70%
 24-33%
Neuropathy
 60%
–
–
Complication
DCCT = The Diabetes Control and Complications Trial.
DCCT Study Group. N Engl J Med. 1993;329:977-986; Ohkubo. Diabetes Res Clin Prac. 1995;28:103-117;
UKPDS Study Group. Lancet. 1998;352:837-853.
© 2005 The Johns Hopkins University School of Medicine.
Hypertension
The Second Leading cause of
Kidney Failure
Recommendations for BP and
RAS Management in CKD
Patient
Group
Goal BP
(mm Hg)
First Line
Adjunctive
+ Diabetes
<130/80
ACE-I or ARB Diuretics then CCB or BB
 Diabetes
+ Proteinuria
<130/80
ACE-I or ARB Diuretics then CCB or BB
 Diabetes
 Proteinuria
<130/80
No specific preference:
Diuretics then ACE-I, ARB, CCB, or BB
EXPECT TO NEED TO USE 3+ AGENTS TO ACHIEVE GOALS
Recommendations largely consistent across JNC 7, ADA, and K/DOQI
BP = blood pressure; RAS = renin angiotensin system; CCB = calcium channel blocker;
BB = b-blocker; JNC 7 = The Seventh Report of the Joint National Committee on Prevention,
Detection, Evaluation, and Treatment of High Blood Pressure.
ADA. Diabetes Care. 2005;28(suppl 1); Chobanian et al. JAMA. 2003;289:2560-2572; Kidney Disease Outcomes
Quality Initiatives (K/DOQI). Am J Kidney Dis. 2004;43(5 suppl 1):S1-S290.
© 2005 The Johns Hopkins University School of Medicine.
ACEI/ARB & Reduced Risk of Rapid GFR
Decline, Kidney Failure, or Death
AASK (N=1094)
RENAAL (N=1513)
IDNT (N=1722)
Composite Risk (%)*
0
-10
-16
-22
-20
-30
-38
-40
-50
Ramipril vs
Metoprolol
P = 0.04
Losartan vs
Placebo
P = 0.02
-20
-23
Irbesartan
vs Placebo Irbesartan
vs Amlodipine
P = 0.02
P = 0.006
Ramipril vs
Amlodipine
P = 0.004
Wright et al for the AASK Study Group. JAMA. 2002;288:2421-2431.
[AASK - African American Study of Kidney Disease and Hypertension]
Brenner et al for the RENAAL Study Investigators. N Engl J Med. 2001;345:861-869.
[RENAAL = Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan]
Lewis et al for the Collaborative Study Group. N Engl J Med. 2001;345:851-860.
[IDNT = Irbesartan in Diabetic Nephropathy Trial.]
© 2005 The Johns Hopkins University School of Medicine.
Patients Reaching End Point* (%)
ACEIs, ARBs, and Combination Therapy
Effects in Nondiabetic Nephropathy
30
Trandolapril (n = 86)
Losartan (n = 89)
Combination (n = 88)
25
20
15
10
5
P = 0.02
0
0
6
12
18
24
Follow-Up (mo)
30
36
*Primary end point: doubling of SCr or kidney failure.
Nakao et al. Lancet. 2003;361:117-124.
© 2005 The Johns Hopkins University School of Medicine.
Relationship Between Achieved BP
and GFR
MAP = Mean Arterial Pressure*
2
eGFR (mL/min/1.73 m) per y
95
98
101
104
107
110
113
116
119
0
r = 0.69
P<0.05
-2
-4
-6
Untreated
Hypertension
-8
-10
-12
130/80
140/90
-14
*MAP = [SBP + (2 × DBP)]/3 mm Hg.
Summary of 9 studies used in figure.
Parving et al. 1989; Viberti et al. 1993; Klahr et al. 1993; Hebert et al. 1994; Lebovitz et al. 1994;
Moschio et al. 1996; Bakris et al. 1996; Bakris et al. 1997; GISEN Group. 1997.
Bakris et al. Am J Kidney Dis. 2000;36:646-661.
© 2005 The Johns Hopkins University School of Medicine.
Anemia
A Modifiable and Funded Risk
Factor
Anemia Prevalence by CKD
Stage
Patients With Anemia* (%)
NHANES III
NHANES 1999-2000
70
60
50
40
30
20
10
0
1
2
CKD Stage
3
4-5
*NHANES participants aged ≥20 y with anemia as defined by WHO criteria: hemoglobin (Hgb)
<12 g/dL for women, and Hgb <13 g/dL for men.
USRDS 2004 Annual Data Report. The data reported here have been supplied by the USRDS. The interpretation and
reporting of these data are the responsibility of the author(s) and in no way should be seen as an official policy or
interpretation of the U.S. government. Available at: www.usrds.org. Accessed 3/28/05.
© 2005 The Johns Hopkins University School of Medicine.
Anemia Treatment Eligibility
• Serum Creatinine (2.0 mg/dl or above)
or
• Creatinine Clearance (45 ml/min or
below) and
• Hemoglobin (11g/dl or below) or
• Hematocrit (33% or below) or
• Symptoms of anemia
Consequences of Anemia in CKD
• Reduced oxygen delivery to tissues
• Decrease in Hgb compensated by increased cardiac
output
• Progressive cardiac damage and progressive renal
damage1
• Increased mortality risk2
• Reduced quality of life (QOL)3
– Fatigue
– Diminished exercise capacity
– Reduced cognitive function
• Left ventricular hypertrophy (LVH)4
1. Silverberg et al. Blood Purif. 2003;21:124-130. 2. Collins et al. Semin Nephrol. 2000;20:345-349; 3. The US
Recombinant Human Erythropoietin Study Group. Am J Kidney Dis. 1991;18:50-59; 4. Levin. Semin Dial.
2003;16:101-105.
© 2005 The Johns Hopkins University School of Medicine.
Clinical Benefit of Anemia Correction:
CHF and CKD
Patients With CHF and Anemia (n = 126, 91% CKD)
Parameter
Before
After
10.3
2.4
-0.95
13.1
2.3
0.27
Hospitalizations
Systolic BP (mm Hg)
3.8
8.9
3.7
132
2.7
2.7
0.2
131
Diastolic BP (mm Hg)
75
76
Hgb (g/dL)
Serum creatinine (g/dL)
∆GFR (mL/min/mo)
NYHA class (0-4)
Fatigue/SOB index (0-10)
NYHA class = New York Heart Association classification;
© 2005 The Johns Hopkins University School of Medicine.
SOB = shortness of breath.
Silverberg et al. Perit Dial Int. 2001;21(suppl 3):S236-S240.
Secondary
Hyperparathyroidism
An Early and Modifiable
Complication of CKD
Calcitriol Decline and iPTH Elevation
as CKD Progresses
CKD Stage 1
5.6 million
Stage 2
5.7 million
Stage 3
7.4 million
Stage 4
300,000
400
40
30
25
300
Low-Normal
Calcitriol
20
200
10
100
High-Normal 65
PTH
iPTH (pg/mL)
Calcitriol
1,25(OH)2D3 (pg/mL)
50
0
105
N = 150.
iPTH = intact PTH.
95
85
75
65
55
45
35
25
15
eGFR (mL/min/1.73 m2)
Adapted from Martinez et al. Nephrol Dial Transplant. 1996;11(suppl 3):22-28.
© 2005 The Johns Hopkins University School of Medicine.
Feedback Loops in SHPT
Decreased Vitamin D Receptors
and Ca-Sensing Receptors
 PTH
 PTH
 Ca++
Bone Disease
Fractures
 Serum P
Bone pain
Marrow fibrosis
Erythropoietin resistance
1,25D
Calcitriol
Systemic Toxicity
CVD
Hypertension
Inflammation
Calcification
Immunological
25D
Renal Failure
Ca = calcium; CVD = cardiovascular disease; P = phosphorus.
Courtesy of Kevin Martin, MB, BCh.
© 2005 The Johns Hopkins University School of Medicine.
Bone Loss Correlates With Severity of
SHPT in CKD Stages 3 and 4
PTH <60 pg/mL
Bone Mineral Density, Z-Score
Spine
PTH 60-120 pg/mL
Hip
PTH >120 pg/mL
Arm
0.00
-0.25
-0.50
-0.75
-1.00
-1.25
-1.50
*
*
-1.75
-2.00
*
-2.25
*P<0.05 compared with patients with PTH in the normal range.
Z-Score = comparison to the mean value for women at a similar risk, including age, weight,
and ethnicity.
Rix et al. Kidney Int. 1999;56:1084-1093.
© 2005 The Johns Hopkins University School of Medicine.
Observed/Expected
Incidence of Hip Fracture*
Bone-Fracture Rate Increases as CKD
Progresses: Fractures in Patients on
Dialysis
100
87
Overall
Male Relative Risk = 4.4
Female Relative Risk = 4.4
99
80
25 20
20
15
10 10
10
7.5
6.4
5
2.4 2.5
4.4 4.4
0
<45
45-54
55-64
65-74
Age (y)
75-84
Total
*Ratio of observed incidence of hip fracture in patients with kidney failure to expected incidence
of hip fracture in the general population.
Adapted from Alem et al. Kidney Int. 2000;58:396-399.
© 2005 The Johns Hopkins University School of Medicine.
Cardiovascular Outcomes Worsen With
CKD Progression: 3-Y Follow-Up by eGFR
Levels
eGFR (mL/min/1.73 m )
2
75
60-74
45-59
<45
Estimated Event Rate (%)
60
P<0.001
50
40
30
20
10
0
Composite
End Point
Death From
CV Causes
Reinfarction
CHF
Stroke
Resuscitation
CHF = congestive heart failure.
Anavekar et al. N Engl J Med. 2004;351:1285-1295.
© 2005 The Johns Hopkins University School of Medicine.
Why Classify Severity as the
Level of GFR?
AJKD 2002: 39(2)
Guideline 4.
Estimation of GFR
AJKD 2002: 39(2)
Guideline 4.
Estimation of GFR (cont’d)
AJKD 2002: 39(2)
Guideline 4.
Estimation of GFR (cont’d)
AJKD 2002: 39(2)
Advantages of Estimating GFR
Using Equations
AJKD 2002: 39(2)
Serum Creatinine
Corresponding to GFR of
60 mL/min/1.73 m2
AJKD 2002: 39(2)
Clearance
and Serum Creatinine with
GFR (Inulin Clearance) in
Patients with Glomerular Disease
AJKD 2002: 39(2)
Estimates of GFR vs. Measured
GFR
in MDRD Study Baseline Cohort
AJKD 2002: 39(2)
Accuracy of Different Estimates of
GFR in Adults
AJKD 2002: 39(2)
Prevalence of Individuals at
Increased Risk for CKD
AJKD 2002: 39(2)
Patients Who Are Aware of
Weak or Failing Kidneys* (%)
Awareness of Early-Stage CKD Is Low
in the US Population
20
18.6
17.9
15
10
5.5
5
0
Albuminuria:
eGFR:
3.9
1.6
1.1
<30
30+
90+
<30
2.9
2.4
30+
60-89
<30
30+ Sex: F
30-59
M
30-59
*Proportion of patients who were told they had weak or failing kidneys, eGFR (mL/min/1.73 m2).
Coresh et al. J Am Soc Nephrol. 2005:16:180-188.
© 2005 The Johns Hopkins University School of Medicine.
Summary
• Over 20 millions Americans have some
degree of CKD & few are aware of it.
• There are interventions to slow the
progression and treat the complications
that are associated with CKD.
• Reporting eGFR can help alert health care
providers that their patient may have CKD
so further workup, education and
interventions can be done.