Recognizing and Treating
Chronic Kidney Disease (CKD)
Presented by
Lori Finley RN, MSN NP-C
St. Joseph’s Medical Center
Objectives
• Identify patients who have or are at risk
for chronic kidney disease(CKD).
• Describe strategies to slow progression
to End-Stage Renal Disease (ESRD).
• Discuss occurrence, prevention, and
treatment of complications and comorbid conditions of CKD.
• Develop strategies for collaborative
treatment of CKD.
Take Home Messages
“ You can’t find what
you’re not looking for!”
“If you wait, it’s too late!”
“Don’t get caught with
your pants down !”
Projected counts of incident &
prevalent ESRD patients through 2020
Figure 2.1 (Volume 2)
counts projected
using a Markov
model. Original
projections used
data through 2000;
new projections
use data through
2006.
•USRDS 2008
Prevalence of Renal
Insufficiency in US (NKDEP)
GFR
(ml/min/1.73 m2) 59-30
Number
of People
29-15
7.6 Million 360,000
< 15
> 300,000
More than 8 million Americans have substantial
kidney impairment,
Coresh, Levey, et al.
and 10 million more have albuminuria.
Problem is bigger than nephrology
1) 7.6 million people with GFR 30-60
ml/min/1.73m2
2) About 4,500 full-time nephrologists
3) Nearly 2,000 new patients per nephrologist
Therefore, 7 new patients per day per nephrologist
Classification tree, with
significant interactions
•Predictor variables: age; DM; HTN; obesity (20-52 yo)
•USRDS 2008
What’s the most common
sign or symptom of early
kidney disease?
Asymptomatic
Definition of CKD
Kidney damage (structural or functional)
OR
GFR < 60 ml/min/1.73 m2 for greater than
3 months
National Kidney Foundation, 2002.
Stages of CKD
Stage
1
0
At

risk
Mild
Kidney
Failure
Kidney
Damage
120
GFR
3
4
Moderate
Kidney
Failure
Severe
Kidney
Failure
2
90
60
30
5
Kidney
Failure
15
NKF-K/DOQI Staging
Classification of CKD
Stage
1
Description
GFR/Focus of Care
Chronic kidney damage >90 ml/min
with normal or  GFR
Screen for CKD &  Risk
2
Mild  GFR
60–89* Diagnose & Treat
to slow progression &
reduce risk
3
Moderate  GFR
30–59 Neph/Tx referral
4
Severe  GFR
15–29 Prepare KRT
5
Kidney failure
<15 Dialysis
GFR: mL/min/1.73 m2
*May be normal for age
National Kidney Foundation, 2009.
High Risk Patients
• Diabetes
• Hypertension
• Aging (>50 years old)
• Racial-ethnic background
(African American,Native American, Asian-American,
Pacific Islander, Latin American, Hispanic)
• Family History of kidney disease
National Kidney Foundation, 2002.
Primary Diagnoses for
Patients Who Start Dialysis
Other
10%
Glomerulonephritis
13%
Diabetes
50%
Hypertension
27%
United States Renal Data System
(USRDS), 2000.
www.hypertensiononline.org
Risk Factors for CKD
Early Detection
• Male gender
• High-protein diet
• Tobacco use
• Hyperlipidemia
• Low Income/education
• Atherosclerosis
• UTI, urinary stones,
lower UT obstruction
• Obesity
• Autoimmune disease
• AKI – Recovery
• Neoplasia
• Exposure to
nephrotoxic drugs
– NSAIDS, Cox 2
– Contrast dye
• Anemia
National Kidney Foundation, 2002.
Recommended Screening Tests
For Patients at Risk for CKD
Screening is the beginning of a complex
management process for CKD.
• Serum creatinine (SCr) – Use prediction
equation
• Blood pressure – Early factor
• Glucose – Early factor
• Urinalysis
• Microalbuminuria/proteinuria – Diabetics
NKF 2009; American Diabetes Association, 2000; McCarthy, 1999.
Measures for Defining CKD
• Glomerular filtration rate (GFR)
– Best indicator, usually estimated
• Serum creatinine (SCr)
– Women 1.2 mg/dl
– Men  1.4 mg/dl
– Over 65 years old >1.2 mg/dL
• Creatinine clearance (Ccr) <60 mL/min
- 24-hour specimen may be required
Comstock, 1997.
Consensus Development Conference Panel, 1994
U.S. Department of Health and Human Services, 2000
CASE
• Case:
– 86-year-old woman, 66-kg body
weight
– Hospitalized March & April,
Hct 16%, GI work-up negative,
Transfused
– May – Admit with weakness
Hct 27.5%, K+ 6.9 mg/dl,
Creatinine 1.5 mg/dl, Ccr 24ml/min.
– Nephrology consult
CASE
• Case:
– What, if any, level of kidney
disease?
None
Mild (GFR 60-90)
Moderate (GFR 30- 60)
Severe (GFR 15-30)
Kidney failure (GFR <15)
Improving Upon SCr Screening
Use Prediction Equation
Cockcroft-Gault (C-G)
Method for Estimating Ccr
Ccr=
(140 – age [y])(body wt [kg]) x 0.85*)
(72)(SCr [mg/dL])
• Example:
– 86-year-old woman, 66-kg body weight,
1.8 mg/dL SCr
• Formula result:
STAGE 4 SEVERE KIDNEY DISEASE
– Ccr= 23 mL/min
* For women ( x 1.0 for men)
Cockcroft, 1976.
MDRD calculation
• Calculation is based on age, gender, race,
creatinine
• Ex: 50yo 60kg white female-creatinine 0.6 or 1
• Creatinine 0.6mg/dl = 112ml/min
• Creatinine 1mg/dl = 62ml/min
• MDRD calculator websites – click on GFR
calculator
• www.kidney.com or www.hdcn.com
Serum creatinine is not a good
indicator of Kidney Function
Prevalence of abnormal GFR values
(< 50 ml/min) by age in pts. with normal
serum creatinine (< 130umol/l [1.5mg/dl])
Age
ALL
< 40
40-49 50-59 60-69 > 70
ALL
2343
503
396
500
476
668
Abn.
GFR
%
387
0
3
5
60
316
15.2
0
0.8
1.6
12.6
47.3
Duncan, Heathcote, Djurdjev, & Levin, 2001.
Creatinine Alone Is Not Accurate for
Predicting Renal Function
• Need to be in steady state
• Diet – Vegans lower
• Less creatinine in malnutrition
• Less muscle mass children, women, elders
• Cimetidine, Septra®, cephalosporins,
ketoacidosis increase creatinine
• ~40% of people with decreased GFR have a
serum creatinine in lab’s normal range
Recommended Screening Tests
for Renal Complications
• Random, spot urine for albumin/creatinine
• Positive if >30 mg/g* or ratio >0.03
• 30 – 300 mg/day albumin excretion =
microalbminuria; >300 macroalbuminuria
• Repeat 2 to 3 times over 6 months, or
confirm with 24-hour collection for
microalbumin
* >30 (mg) albumin/ (g) creatinine
National Kidney Foundation, 2002, 2009.
Who Should Be Treated for CKD?
• Diabetics with urine albumin/creatinine
ratios more than 30mg albumin/1 gram
creatinine.
• Non-diabetics with urine albumin/creatinine
ratios more than 300mg albumin/1 gram
creatinine.
OR
• Non-diabetics with estimated GFR less
than 60 ml/min/1.73m2.
Goals of Treatment
Early Detection
of CKD
Delay
progression
Prevent
complications
Treat comorbidities
Prepare
for RRT
BP control
Anemia
Cardiac disease
Educate patient
Malnutrition
Hypertension
Select RRT
modality
Bone disease
Diabetes
BS control
Avoid
nephrotoxins
Acidosis
Create access
and initiate
dialysis in a
timely fashion
Treat dyslipidemia
Lifestyle
Adapted from Pereira, 2000.
Goals of Treatment
Early
Detection
of CKD
Delay
progression
BP control
Prevent
complications
Treat comorbidities
Prepare
for RRT
Avoid
nephrotoxins
Treat Proteinuria
BS Control
Lifestyle
Treat Dyslipidemia
Adapted from Pereira, 2000.
Delay Progression:
Hypertension and Proteinuria
GOALS:
With Proteinuria
Without Proteinuria
125/75
or lower
130/80 mm Hg
DM/CKD
(JNC VII, NKF))
Proteinuria
< 500 - 1000
mg/g
National Institutes of Health; National
Heart, Lung, and Blood Institute; National
High Blood Pressure Program, 1997.
Blood Pressure Is Poorly
Controlled in CKD
130/85 mm Hg
140/90
11%
mm Hg
62%
140/90
27%
mm Hg
Hypertension
Affects 50 million in US
1 Billion worldwide
Coresh, Wei, McQuillan, Brancati, Levey, Jones, et al., 2001.
Effect of Blood Pressure on
Progression of Nephropathy*
MAP (mm Hg)
95
98
101
104
107
110
113
116
119
0
GFR
(mL/min/year)
-2
r = 0.69; P<0.05
-4
-6
Untreated
HTN
-8
-10
-12
130/85
140/90
-14
*Summary of trials using ACE
inhibitors to achieve target BP
Bakris, 1998; Sheinfeld & Bakris, 1999.
Chronic Renal Disease:
Initial Treatment Recommendations
CKD
Clcr <60 mL/min
CrSer >1.4 mg/dL*
130/80
Microalbuminuria
(only Abnormality)
130/80
Proteinuria
Diabetes Mellitus
*for women, CR >1.2 mg/dL
ACE
Inhibitor
(or ARB)
Start
And
Titrate
To Maximum
Tolerable
Dose
www.hypertensiononline.org
Delay Progression:
Treat Hypertension and Proteinuria
Agent
Effect
ACE Inhibitors *
Proteinuria,  Decline of GFR,
CHF, CAD, Post MI, Stroke Pre.
ARBs*
Proteinuria,  Decline of GFR,
CHF
Diuretic
Thiazide/Loop
Aldosterone
Receptor Blockers
* Monitor K and Cr.
Enhance antiproteinuric
effect, CHF, CAD, Stroke Pre.
CHF, Post MI
JNC JAMA 2003
Flack, Prem. On KD, 1998
Delay Progression:
Treat Hypertension and Proteinuria
Agent
Effect
CCBs
(calcium channel blockers)
 Proteinuria, CAD, Arrhythmias
Non-dihydropyridine
CCBs
Dihydropyridine
Beta
Blockers
Very effective in lowering BP
Don’t use alone
 Proteinuria, CAD
Post MI, CHF, arrhythmia
JNC VII, JAMA, 2003
Flack, Prem. On KD, 1998
Delay Progression:
Treat Hypertension and Proteinuria
Agent
Central alphaand Beta-blockers
Others:
Alpha blockers
Central alpha2-agonist
Vasodilators
Combinations
Effect
CHF, Anti-oxidants
Lower BP
BPH, + lipoprotein fractions
Useful in BP emergencies
Effective in severe hypertension
Decrease number of Meds
JNC VII, JAMA, 2003
Flack, Prem. On KD, 1998
Monitoring GFR w/ BP meds
NKF-K/DOQI guidelines
GFR monitoring w/ ACE/ARB
NKF-K/DOQI guidelines
ACE/ARB monitoring intervals
NKF-K/DOQI guidelines
Delay Progression: Diabetes
• CKD – Peripheral insulin resistance, acidosis,
decreased insulin excretion in uremia
• Tight control (HgbA1C < 7%) slows progression
of renal disease in Type I and II
• Test for microalbuminuria at time of diagnosis
and annually
• Suspect nephropathy if retinopathy is present
• Treatment cautions:
No Metformin if <40ml/min – Lactic acidosis
Sulfonylureas accumulate in renal failure
Wolf & Ritz, JASN, 2003
Insulin degraded by the kidney
Glitazones aggravate edema and CHF
Delay Progression:
Treat Hyperlipidemia
• Meta analysis of 12 studies showed lipid lowering
agents slowed GFR decline *
• Monitor for Dyslipidemia (TG>150, LDL>100, HDL<40)
• High risk – Goal: LDL < 100
Non-HDL < 130
• Diet
• Statins appear safe
• Caution fibric acid derivatives
* Fried, Orchard, Kasiske. KI, 2001
CKD patients receiving a lipid test
in the two years prior to ESRD,
by age & race/ethnicity
incident ESRD patients, age 67 & older at initiation; albumin & lipid tests identified from Medicare claims during the
two-year period prior to ESRD.
•USRDS 2008
Delay Progression:
Avoidance of Nephrotoxic Substances
• NSAIDs (COX-2 inhibitors, ibuprofen)
are potentially nephrotoxic.
• Avoid other nephrotoxic substances
(intravenous dye, aminoglycosides,
amphotericin B, cyclosporin,
tacrolimus, lithium, cisplatin, gold).
• ACE inhibitors/ARBs.
National Kidney Foundation, 2002.
Delay Progression:
Lifestyle/Nutritional Restrictions
• Exercise
• Cessation of smoking (increased rate of
progression of CKD)
• Sodium restriction
– Hypertensive/nephropathy patients  2000
mg/day
• Fluid Restriction 1,000ml/day plus output
• Potassium – Low-K diet, diuretics, treat acidosis
• Protein (controversial)
American Diabetes Association, 2001b.
– Microalbuminuria: 0.8 g/kg/day
– Decreasing GFR: 0.6 g/kg/day
CKD patients receiving an albumin
test in the two years prior to ESRD,
by age & race/ethnicity
incident ESRD patients, age 67 & older at initiation; albumin & lipid tests identified from Medicare claims during the
two-year period prior to ESRD.
•USRDS 2008
Delay Progression:
Treat Hypertension and Proteinuria
Lifestyle modifications
Weight Loss
DASH Diet
10 kg loss
Diet rich in fruit
vegetables
Low-Sodium Restrict sodium
Diet
intake
Physical
30 minutes/day
Activity
most days
Mod. Alcohol 2 drinks/day men
Consumption 1 drink/day/women
5-20 mm Hg
8-14 mm Hg
2-8 mm Hg
4-9 mm Hg
2-4 mmHg
Goals of Treatment
Early
Detection
of CKD
Delay
progression
Prevent
complications
Prepare
for RRT
Treat comorbidities
Anemia
Cardiac disease
Malnutrition
Hypertension
Bone disease
Diabetes
Acidosis
Adapted from Pereira, 2000.
Treat Complications and Comorbidities Associated With CKD
•
•
•
•
Anemia
Malnutrition
Bone disease
Metabolic acidosis
• Cardiovascular disease
• Hypertension
• Diabetes
.
Cumulative percentage of patients
receiving hemoglobin testing in the
12 months prior to ESRD
incident ESRD patients with coverage during entire period. Medicare: ESRD patients age 67 & older. Medstat: all
ESRD patients with fee-for-service coverage during study period. Ingenix i3: all ESRD patients.
•USRDS 2008
Erythropoiesis in CKD
Iron
Erythroid
marrow
X
Erythropoietin
RE
cells
Red blood cells
O2 delivery
Adapted from Hillman, 1998.
RE=reticuloendothelial
Anemia Starts Early in CKD and
Worsens With Disease Progression
Prevalence of Anemia (%)
100%
N = 1,658*
10%
80%
33%–36%
30%–32.9%
< 30%
15%
60%
15%
8%
40%
20%
17%
8%
9%
5%
14%
20%
<2
2–2.9
62%
67.5%
>4
Start of Dialysis
†
(n = 131,484)
43%
0%
3–3.9
Serum Creatinine Level (mg/dL)
* Kausz, Steinberg, Nissenson, & Pereira, 2002..
† Obrador, Ruthazer, Arora, Kausz, & Pereira, 1999.
Anemia Is a Mortality Multiplier
Medicare 5% Sample 1996-1997 2-Year Followup, Adjusted for Age, Gender, and Race
8
7.3
Relative Risk
7
6
5
3.7
4
4
2.9
3
2
3.7
1
1.5
2
2
1
0
None
Diabetes Anemia
CKD
CHF
Analysis performed by Minneapolis Medical Research Foundation.
DM/CHF CKD/
CHF/ DM/CHF
only
Anemia Anemia /CKD/
Anemia
Anemia NKF KDOQI guidelines
www.kidney.org/professionals/kdoqi/guidelines
•  Hemoglobin (<11-12gm/dl)
•  Hematocrit (<33-37%)
• Iron deficiency: Normocytic,
normochromic
•  Ferritin (<100ng/ml) [<12 absolute
iron deficiency]
•  % Saturation (<20%) [<16% absolute
iron deficiency]
Anemia Evaluation
• Iron stores
• Folate or vitamin B deficiency
• Potential sources of blood loss (gi,
menses)
• Infection/inflammation (diabetes,
systemic lupus, rheumatoid arthritis)
Erythropoietin Therapy
• H&H <10gm/dl and <32
• Symptoms: SOB, fatigue, tachycardia,
cold intolerance
• Subcutaneous – Weekly or bimonthly
• Monitoring
– B/P
– Labs
– seizures
Treat Anemia
• Work up for anemia
• Treat with erythropoietin stimulating
agent (ESA)
• Similar side effect profile
• Dosing varies by ESA and patient
response
• Monitor BP
National Kidney Foundation, 2002.
Cumulative percentage of patients
receiving EPO/DPO in the 12
months prior to ESRD
Medstat: incident ESRD patients with fee-for-service & drug coverage during entire study period. Ingenix i3: incident
ESRD patients with coverage during entire period.
•USRDS 2008
Unadjusted survival probabilities in
patients with or without CKD &
walking disabilities (Medicare 65+yo)
•CKD w/o walking
•Disability -87%
•CKD w/
•Walking disability 77%
general Medicare patients, 2005, age 65 & older, with Medicare as primary payor & surviving through the end of 2005.
Walking disability diagnoses include 782.1 “abnormal gait,” 719.7 “difficulty walking,” V15.88 “history of fall,” or an
E-code indicating a fall. Assistive devices are canes, walkers, & wheelchairs. Comorbidities identified from Medicare
claims during 2005; one-year survival & mortality determined from January 1, 2006.
•USRDS 2008
Bone Disease
• Begins in stage 3
• Phosphorus retention (nl 3.5-5.5 mg/dl)
• Inadequate vitamin D conversion
• Decreased gi calcium absorption (nl 8.4-9.5 mg/dl)
• 2nd hyperparathyroidism develops (intact PTH
target goals) 35-70 pg/ml stage 3; 70-110 stage 4;
150-300 stage 5
Renal Osteodystrophy
• Accurate diagnosis with bone biopsy but
rarely done
• Goal to prevent high or low bone turnover dz
• Estimate when GFR <60ml/min (stage 3)
•  Intact PTH
•  Phosphorus
•  Calcium
• Calcium X phosphorus product <55 is goal
Therapy Goals for Renal
Osteodystrophy
• Prevent/control 2nd hyperparathyroidism
• Phosphorus control w/ diet and/or calcium
supplements
• Active vitamin D either as calcitriol or an
analog paricalcitol or doxercalciferol
• Cinacalcet alters Ca sensing PTH cells
• Calcium replacement
• Must monitor labs with therapy
Phosphorus and GFR
NKF-K/DOQI guidelines
Metabolic Acidosis
• Inadequate excretion of hydrogen and
ammonium
• Inadequate production of bicarbonate
• Consequences include increased serum
potassium
Adjusted hazard ratio of
mortality: Medicare patients
•Pts w/ CHF
Medicare-only: general Medicare patients entering Medicare before
January 1, 2004, alive & age 66 or older on December 31. Patients
enrolled in an HMO, with Medicare as secondary payor, diagnosed with
ESRD during the year, or enrolled in Medicaid in 2004 are excluded.
Comorbidity groups are mutually exclusive, & CKD, diabetes, & CHF
are defined during 2004. Patients are followed for two years from
January 1, 2005, to December 31, 2006.
•USRDS 2008
Cardiovascular Disease:
Prevalence in CKD
Framingham Heart Study
18
% Male Patients
16
Normal SCr
(n=2591)
14
12
Elevated SCr
(1.5–3.0 mg/dL,
n=246)
10
8
6
4
2
0
CVD
CHD
CHF
LVH
Culleton, Larson, Wilson, Evans, Parfrey, & Levy, 2001.
Predictors of mortality in the
Medicare-only population
Figure 3.17 (Volume 1)
•CKD/DM/CHF
•CKD/CHF
point prevalent general Medicare patients entering Medicare
before January 1 of each period, alive & age 66 or older on
December 31. Patients enrolled in an HMO, with Medicare as
secondary payor, diagnosed with ESRD during the year, or
enrolled in Medicaid during the period are excluded. CKD,
diabetes, & CHF defined during each period; comorbidity
groups are mutually exclusive; patients are followed one year
from January 1, to December, 31 of the next year.
•USRDS 2008
Cardiovascular Mortality
Annual Mortality (%)
100
Dialysis Population (DP)
GP Male
10
GP Female
GP Black
1
GP White
DP Male
0.1
DP Female
General Population (GP)
0.01
DP Black
DP White
25–34 35–44 45–54 55–64 65–74 75–84
>85
Age (years)
Adapted from Sarnak & Levey, 2000.
Risk Factors for
Cardiac Disease in CKD
Traditional
Nontraditional
• Hypertension
• Anemia
• Diabetes
• Age
• Inflammation
•
•
•
•
Smoking
Dyslipidemia
Obesity
Inactivity
• Oxidative stress
• Hyperhomocysteinemia
• Ca/Phos metabolism
• Fluid overload
• Hypoalbumin
• Uremic toxins
• GFR < 60 ml/min
• Family history
Sarnak & Levey, 2000.
Block, Hulbert-Shearton, Levin, & Port, 1998.
Kitiyakara, Gonin, Massy, & Wilcox, 2000.
Likelihood of death vs. ESRD
in the Medicare population
•90%
•No CKD
•~68%
•Alive &
•no ESRD
1: non-CKD, NDM, non-CHF 2: CKD only (NDM, non-CHF) 3: CKD + DM 4: CKD + CHF 5: CKD + DM + CHF
point prevalent general Medicare patients entering Medicare before January 1, 2004, alive & age 66 or older on
December 31, & followed for two years. Patients enrolled in an HMO, with Medicare as secondary payor, or diagnosed
with ESRD during the year are excluded. CKD, diabetes, & CHF defined during 2004. Comorbidity groups not
mutually exclusive.
•USRDS 2008
Why Treat CKD and prevent ESRD?
Expected Years Remaining*
Survival in ESRD
35
ESRD patients lose
approximately 80% of remaining
years that the general population
is expected to live.
30
20.4
Cost of ESRD Care – $20 Billion
20
10
4.3
2.5
0
* Based on adult, age 59 years
Obrador et al., 1999.
USRDS, 1999.
Definable Target Treatments
• Blood pressure < 130/80
• Proteinuria < 500mg – 1gm/day
• Anemia Hgb 11-12
• Ca, Phosphate, iPTH – Normal values
• Nutrition – HCO3 = Normal
Albumin = Normal
• Sequential measurement of kidney function
• Predict progression
• Education and preparation
RPA Clinical Practice Guideline, 2002..
Benefits of Early Intervention in
the Management of CKD
• Delayed progression of CKD
• Decreased complications and comorbid conditions
• Improved dialysis outcomes
• Better educated and prepared
patients
Pereira, 2000.
References
American Diabetes Association (ADA). (2000). Standards of medical care for patients with
diabetes mellitus. Diabetes Care, 23(Suppl 1), S32-S42.
American Diabetes Association (ADA). (2001a). Diabetic nephropathy. Diabetes Care, 24(Suppl
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