Recognizing and Treating Chronic Kidney Disease (CKD)

1
Recognizing and Treating Chronic Kidney Disease
(CKD)

• Presented by
• Lori Finley RN, MSN NP-C
• St. Josephs Medical Center

2
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 co-morbid conditions of CKD.
• Develop strategies for collaborative treatment of
  CKD.

3
Take Home Messages
You cant find what youre not looking for!
If you wait, its too late!
Dont get caught with your pants down !
4
Projected counts of incident prevalent ESRD
patients through 2020Figure 2.1 (Volume 2)
counts projected using a Markov model. Original
projections used data through 2000 new
projections use data through 2006.

• USRDS 2008

5
Prevalence of Renal Insufficiency in US (NKDEP)
GFR (ml/min/1.73 m2) 59-30 29-15
lt 15 Number of People 7.6 Million
360,000 gt 300,000
More than 8 million Americans have substantial
kidney impairment, and 10 million more have
albuminuria.
Coresh, Levey, et al.
6
Problem is bigger than nephrology

• 7.6 million people with GFR 30-60 ml/min/1.73m2
• About 4,500 full-time nephrologists
• Nearly 2,000 new patients per nephrologist
• Therefore, 7 new patients per day per nephrologist

7
Classification tree, with significant
interactions

• Predictor variables age DM HTN obesity (20-52
  yo)

• USRDS 2008

8

• Whats the most common sign or symptom of early
  kidney disease?

Asymptomatic
9
Definition of CKD

• Kidney damage (structural or functional)
• OR
• GFR lt 60 ml/min/1.73 m2 for greater than 3 months

National Kidney Foundation, 2002.
10
Stages of CKD
Stage
1
3
0
2
4
5
Kidney Failure
Kidney Damage
At ? risk
Mild Kidney Failure
Moderate Kidney Failure
Severe Kidney Failure
15
120
90
60
30


GFR
11
NKF-K/DOQI Staging Classification of CKD
GFR/Focus of Care
Description
Stage
Chronic kidney damage with normal or ? GFR
gt90 ml/min Screen for CKD ? Risk
1
6089 Diagnose Treat to slow progression
reduce risk
Mild ? GFR
2
3
3059 Neph/Tx referral
Moderate ? GFR
1529 Prepare KRT
Severe ? GFR
4
5
Kidney failure
lt15 Dialysis
GFR mL/min/1.73 m2 May be normal for age
National Kidney Foundation, 2009.
12
High Risk Patients

• Diabetes
• Hypertension
• Aging (gt50 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.
13
Primary Diagnoses for Patients Who Start Dialysis
Other 10
Diabetes 50
Glomerulonephritis 13
Hypertension 27
United States Renal Data System (USRDS), 2000.
www.hypertensiononline.org
14
Risk Factors for CKDEarly Detection

• Male gender
• Tobacco use
• Low Income/education
• UTI, urinary stones, lower UT obstruction
• Autoimmune disease
• AKI Recovery
• Neoplasia
• Anemia

• High-protein diet
• Hyperlipidemia
• Atherosclerosis
• Obesity
• Exposure to nephrotoxic drugs
• NSAIDS, Cox 2
• Contrast dye

National Kidney Foundation, 2002.
15
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.
16
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 gt1.2 mg/dL
• Creatinine clearance (Ccr) lt60 mL/min
• - 24-hour specimen may be required

Comstock, 1997. Consensus Development Conference
Panel, 1994 U.S. Department of Health and Human
Services, 2000
17
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

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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 lt15)

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Improving Upon SCr ScreeningUse 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
• Ccr 23 mL/min

STAGE 4 SEVERE KIDNEY DISEASE
For women ( x 1.0 for men)
Cockcroft, 1976.
20
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

21
Serum creatinine is not a good indicator of
Kidney Function
Prevalence of abnormal GFR values
(lt 50 ml/min) by age in pts. with normal serum
creatinine (lt 130umol/l 1.5mg/dl)
Age ALL lt 40 40-49 50-59 60-69 gt 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.

22
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 labs normal range

23
Recommended Screening Tests for Renal
Complications

• Random, spot urine for albumin/creatinine
• Positive if gt30 mg/g or ratio gt0.03
• 30 300 mg/day albumin excretion
  microalbminuria gt300 macroalbuminuria
• Repeat 2 to 3 times over 6 months, or confirm
  with 24-hour collection for microalbumin

National Kidney Foundation, 2002, 2009.
gt30 (mg) albumin/ (g) creatinine
24
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.

25
Goals of Treatment
Early Detection of CKD
Delay progression
Prevent complications
Treat co- morbidities
Prepare for RRT
Anemia
Cardiac disease
Educate patient
BP control
Malnutrition
Hypertension
Select RRT modality
BS control
Bone disease
Diabetes
Create access and initiate dialysis in a timely
fashion
Acidosis
Avoid nephrotoxins
Treat dyslipidemia
Lifestyle
Adapted from Pereira, 2000.
26
Goals of Treatment
Early Detection of CKD
Delay progression
Prevent complications
Treat co- morbidities
Prepare for RRT
BP control
Avoid nephrotoxins
Treat Proteinuria
Lifestyle
BS Control
Treat Dyslipidemia
Adapted from Pereira, 2000.
27
Delay Progression Hypertension and Proteinuria
GOALS With Proteinuria
Without Proteinuria
130/80 mm Hg DM/CKD (JNC VII, NKF))
125/75 or lower
Proteinuria lt 500 - 1000 mg/g
National Institutes of Health National Heart,
Lung, and Blood Institute National High Blood
Pressure Program, 1997.
28
Blood Pressure Is Poorly Controlled in CKD
?130/85 mm Hg
?140/90 mm Hg
11
?140/90 mm Hg
27
62
Hypertension Affects 50 million in US 1 Billion
worldwide
Coresh, Wei, McQuillan, Brancati, Levey, Jones,
et al., 2001.
29
Effect of Blood Pressure on Progression of
Nephropathy
MAP (mm Hg)
95
98
101
104
107
110
113
116
119
0
-2
r 0.69 Plt0.05
-4
-6
GFR (mL/min/year)
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.
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Chronic Renal DiseaseInitial Treatment
Recommendations
CKD Clcr lt60 mL/min CrSer gt1.4 mg/dL
ACE Inhibitor (or ARB) Start And Titrate To
Maximum Tolerable Dose
?130/80
Microalbuminuria (only Abnormality)
?130/80
Proteinuria
Diabetes Mellitus
for women, CR gt1.2 mg/dL
www.hypertensiononline.org
32
Delay Progression Treat Hypertension and
Proteinuria
Effect
Agent
ACE Inhibitors ARBs

• Proteinuria, ? Decline of GFR, CHF, CAD, Post MI,
  Stroke Pre.

• Proteinuria, ? Decline of GFR, CHF

Diuretic Thiazide/Loop
Enhance antiproteinuric effect, CHF, CAD, Stroke
Pre.
Aldosterone Receptor Blockers
CHF, Post MI
Monitor K and Cr.
JNC JAMA 2003 Flack, Prem. On KD, 1998
33
Delay Progression Treat Hypertension and
Proteinuria
Effect
Agent
CCBs (calcium channel blockers) Non-dihyd
ropyridine
? Proteinuria, CAD, Arrhythmias
CCBs Dihydropyridine
Very effective in lowering BP Dont use
alone
? Proteinuria, CAD Post MI, CHF, arrhythmia
Beta Blockers
JNC VII, JAMA, 2003 Flack, Prem. On KD, 1998
34
Delay Progression Treat Hypertension and
Proteinuria
Effect
Agent
Central alpha- and Beta-blockers
CHF, Anti-oxidants
Others Alpha blockers Central
alpha2-agonist Vasodilators
Lower BP BPH, lipoprotein fractions Useful in
BP emergencies Effective in severe hypertension

Combinations
Decrease number of Meds
JNC VII, JAMA, 2003 Flack, Prem. On KD, 1998
35
Monitoring GFR w/ BP meds NKF-K/DOQI guidelines
36
GFR monitoring w/ ACE/ARB NKF-K/DOQI guidelines
37
ACE/ARB monitoring intervals NKF-K/DOQI
guidelines
38
Delay Progression Diabetes

• CKD Peripheral insulin resistance, acidosis,
  decreased insulin excretion in uremia
• Tight control (HgbA1C lt 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
  lt40ml/min Lactic acidosis Sulfonylureas
  accumulate in renal failure Insulin degraded by
  the kidney Glitazones aggravate edema and CHF

Wolf Ritz, JASN, 2003
39
Delay Progression Treat Hyperlipidemia

• Meta analysis of 12 studies showed lipid lowering
  agents slowed GFR decline
• Monitor for Dyslipidemia (TGgt150, LDLgt100,
  HDLlt40)
• High risk Goal LDL lt 100
  Non-HDL lt 130
• Diet
• Statins appear safe
• Caution fibric acid derivatives

Fried, Orchard, Kasiske. KI, 2001
40
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

41
Delay ProgressionAvoidance 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.
42
Delay ProgressionLifestyle/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)
• Microalbuminuria 0.8 g/kg/day
• Decreasing GFR 0.6 g/kg/day

American Diabetes Association, 2001b.
43
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

44
Delay Progression Treat Hypertension and
Proteinuria
Lifestyle modifications
Weight Loss 10 kg loss 5-20 mm Hg
DASH Diet Diet rich in fruit vegetables 8-14 mm Hg
Low-Sodium Diet Restrict sodium intake 2-8 mm Hg
Physical Activity 30 minutes/day most days 4-9 mm Hg
Mod. Alcohol Consumption 2 drinks/day men 1 drink/day/women 2-4 mmHg
45
Goals of Treatment
Early Detection of CKD
Delay progression
Prevent complications
Treat co- morbidities
Prepare for RRT
Anemia
Cardiac disease
Malnutrition
Hypertension
Diabetes
Bone disease
Acidosis
Adapted from Pereira, 2000.
46
Treat Complications and Co-morbidities Associated
With CKD

• Anemia
• Malnutrition
• Bone disease
• Metabolic acidosis
• Cardiovascular disease
• Hypertension
• Diabetes

.
47
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

48
Erythropoiesis in CKD
X
Iron
Erythroid marrow
Erythropoietin
RE cells
Red blood cells
O2 delivery
Adapted from Hillman, 1998.
REreticuloendothelial
49
Anemia Starts Early in CKD and Worsens With
Disease Progression

Kausz, Steinberg, Nissenson, Pereira, 2002..
Obrador, Ruthazer, Arora, Kausz, Pereira,
1999.
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Anemia Is a Mortality MultiplierMedicare 5
Sample 1996-1997 2-Year Follow-up, Adjusted for
Age, Gender, and Race
Analysis performed by Minneapolis Medical
Research Foundation.
52
Anemia NKF KDOQI guidelines www.kidney.org/profes
sionals/kdoqi/guidelines

• ? Hemoglobin (lt11-12gm/dl)
• ? Hematocrit (lt33-37)
• Iron deficiency Normocytic, normochromic
• ? Ferritin (lt100ng/ml) lt12 absolute iron
  deficiency
• ? Saturation (lt20) lt16 absolute iron
  deficiency

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Anemia Evaluation

• Iron stores
• Folate or vitamin B deficiency
• Potential sources of blood loss (gi, menses)
• Infection/inflammation (diabetes, systemic lupus,
  rheumatoid arthritis)

54
Erythropoietin Therapy

• HH lt10gm/dl and lt32
• Symptoms SOB, fatigue, tachycardia, cold
  intolerance
• Subcutaneous Weekly or bimonthly
• Monitoring
• B/P
• Labs
• seizures

55
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.
56
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

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Unadjusted survival probabilities in patients
with or without CKD walking disabilities
(Medicare 65yo)

• 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

59
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

60
Renal Osteodystrophy

• Accurate diagnosis with bone biopsy but rarely
  done
• Goal to prevent high or low bone turnover dz
• Estimate when GFR lt60ml/min (stage 3)
• ? Intact PTH
• ? Phosphorus
• ? Calcium
• Calcium X phosphorus product lt55 is goal

61
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

62
Phosphorus and GFR NKF-K/DOQI guidelines
63
Metabolic Acidosis

• Inadequate excretion of hydrogen and ammonium
• Inadequate production of bicarbonate
• Consequences include increased serum potassium

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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

68
Cardiovascular Disease Prevalence in CKD

Framingham Heart Study
Normal SCr (n2591)
Elevated SCr (1.53.0 mg/dL, n246)
Male Patients
CVD
CHF
LVH
CHD
Culleton, Larson, Wilson, Evans, Parfrey, Levy,
2001.
69
Predictors of mortality in the Medicare-only
populationFigure 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

70
Cardiovascular Mortality
100
Dialysis Population (DP)
10
1
Annual Mortality ()
0.1
General Population (GP)
0.01
2534
3544
4554
5564
6574
7584
gt85
Age (years)
Adapted from Sarnak Levey, 2000.
71
Risk Factors for Cardiac Disease in CKD

• Nontraditional
• Anemia
• Inflammation
• Oxidative stress
• Hyperhomocysteinemia
• Ca/Phos metabolism
• Fluid overload
• Hypoalbumin
• Uremic toxins

• Traditional
• Hypertension
• Diabetes
• Age
• Smoking
• Dyslipidemia
• Obesity
• Inactivity
• GFR lt 60 ml/min
• Family history

Sarnak Levey, 2000. Block, Hulbert-Shearton,
Levin, Port, 1998. Kitiyakara, Gonin, Massy,
Wilcox, 2000.
72
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

73
Why Treat CKD and prevent ESRD?Survival in ESRD
35
ESRD patients lose approximately 80 of remaining
years that the general population is expected to
live. Cost of ESRD Care 20 Billion
30
20.4
20
Expected Years Remaining
10
4.3
2.5
0
US Population
Lung Cancer
ESRD
Based on adult, age 59 years
Obrador et al., 1999. USRDS, 1999.
74
Definable Target Treatments

• Blood pressure lt 130/80
• Proteinuria lt 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..
75
Benefits of Early Intervention in the Management
of CKD

• Delayed progression of CKD
• Decreased complications and co-morbid conditions
• Improved dialysis outcomes
• Better educated and prepared patients

Pereira, 2000.
76
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 1),
  S69-S72.
• American Diabetes Association (ADA). (2001b).
  Nutrition recommendations for patients with
  diabetes mellitus. Diabetes Care, 24(Suppl 1),
  S44-S47.
• Bakris, G.L., Williams, M., Dworkin, L., Elliott,
  W.J., Epstein, M. Toto, R., et al, (2000).
  Preserving renal function in adults with
  hypertension and diabetes A consensus approach.
  The National Kidney Foundation Hypertension and
  Diabetes Executive Committees Working Group. Am
  Journal of Kidney Disease, 36(3), 646-661.
• Bakris, G.L. (1998). Progression of diabetic
  nephropathy A focus on arterial pressure level
  and methods of reduction. Diabetes Research and
  Clinical Practice, 39(Suppl), S39-S42.
• Bakris, G.L., Slataper, R., Vicknair, N.,
  Sadler, R. (1994). ACE inhibitor mediated
  reductions in renal size and microalbuminuria in
  normotensive, diabetic subjects. Journal of
  Diabetes Complications, 8(1), 2-6.
• Besarab, A., Levin, A. (2000). Defining a renal
  anemia management period. American Journal of
  Kidney Disease, 36(Suppl 3), S13-S23.
• Block, G.A., Hulbert-Shearton, T.E., Levin, N.W.,
  Port, F.K. (1998). Association of serum
  phosphorus and calcium X phosphate product with
  mortality risk in chronic hemodialysis patients
  A national study. American Journal of Kidney
  Disease, 31, 607.

77
References

• Bolton, W.K., Kliger, A.S. (2000). Chronic
  renal insufficiency Current understandings and
  their implications. American Journal of Kidney
  Disease, 36(6), S4-S12.
• Brenner, B.M., Cooper, M.E., de Zeenw, D., Keane,
  W.F., Mitch, W.F., Parving, H.H., et al. (2001).
  Effects of losartan on renal and cardiovascular
  outcomes in patients with type 2 diabetes and
  nephropathy. New England Journal of Medicine,345,
  861-869.
• Cockcroft, D.W., Gault, M.H. (1976). Prediction
  of creatinine clearance from serum creatinine.
  Nephron, 16, 31-41.
• Comstock, T.J. (1997). Quantification of renal
  function. In T.J. Dipiro, R.L. Talbert, G.C. Yee,
  G.R., Matzke, B.G. Wells, L.M. Posey (Eds.),
  Pharmacotherapy A path physiologic approach (3rd
  ed.). Stamford, CT Appleton and Lange.
• Consensus Development Conference Panel. (1994).
  Morbidity and mortality of renal dialysis An NIH
  consensus conference statement. Annals of
  Internal Medicine, 121, 62-70.
• Coresh, J., Astor, B.C., Greene, T., Eknoyan, G.,
  Levey, A.S. (2003). Prevalence of chronic kidney
  disease and decreased kidney function in the
  adult US population Third National Health and
  Nutrition Examination Survey. American Journal of
  Kidney Disease, 41(1-12).
• Coresh, J., Wei, G.L., McQuillan, G., Brancati,
  F.L., Levey, A.S., Jones, C., et al. (2001).
  Prevalence of high blood pressure and elevated
  serum creatinine level in the United States
  Findings from the Third National Health and
  Nutrition Examination Survey (1988-1994).
  Archives of Internal Medicine, 161(9), 1207-1216.
• Culleton, B.F., Larson, M.G., Wilson, P.W.,
  Evans, J.C., Parfrey, P.S., Levy, D. (1999).
  Cardiovascular disease and mortality in a
  community-based cohort with mild renal
  insufficiency. Kidney International, 56,
  2214-2219.

78
References

• Del Vecchio, L., Locatelli, F. (2001). The
  renoprotective effect of combined
  antihypertensive drugs. Journal of Nephrology,
  14, 7-14.
• Duncan, L., Heathcote, J., Djurdjev, O., Levin,
  A. (2001). Screening for renal disease using
  serum creatinine Who are we missing? Nephrology
  Dialysis Transplantation, 16, 1042-1046.
• Flack JM. Therapy of hypertension. In Greenberg
  A, ed. (1998). Primer on Kidney Diseases. San
  Diego, CA Academic Press, 506-516
• Fried, L.F, Orchard, T.J., Kasiske, B.L. (2001)
  Effect of lipid reduction on the progression of
  renal disease a meta-analysis. Kidney
  International, Jan59(1), 260-9.
• Gaspari, F., Perico, N., Matalone, M., Signorini,
  O., Azzollini, N. Mister, M., et al. (1998).
  Precision of plasma clearance of iohexol for
  estimation of GFRin patients with renal disease.
  Journal of the American Society of Nephrology,
  9(2), 310-313.
• Henrich, W.L., Agodoa, L.E., Barrett, B.,
  Bennett, W.M., Blantz, R.C., et al. (1996).
  Analgesics and the kidney Summary and
  recommendations to the scientific advisory board
  of the National Kidney Foundation from an ad hoc
  committee of the National Kidney Foundation.
  American Journal of Kidney Disease, 27, 162-165.
• Hillman, R.S. (1998). Anemia. In A.S. Fauci, E.
  Braunwald, K.J. Isselbacher KJ,, J.D. Wilson,
  J.B. Martin, D.L. Kasper, et al. (Eds).
  Harrisons principles of internal medicine (14th
  ed.) (pp. 334-339). New York McGraw-Hill.
• Jafar, T.H., Schmid, C.H., Landa, M., Giatras,
  I., Toto, R., Remuzzi, G., et al. (2001).
  Angiotensin converting enzyme inhibitors and
  progression of nondiabetic renal disease A
  meta-analysis of patient level data. Annals of
  Internal Medicine, 135, 73-87.
• Kausz, A.T., Steinberg, E.P., Nissenson, A.R.,
  Pereira, B.J.G. (2002). Prevalence and management
  of anemia among patients with chronic kidney
  disease in a health maintenance organization.
  Disease Management and Health Outcomes, 10(8),
  505-513.

79
References

• Kitiyakara, C., Gonin, J., Massy, Z., Wilcox,
  C.S. (2000). Non-traditional cardiovascular
  disease risk factors in end-stage renal disease
  Oxidate stress and hyperhomocysteinemia. Curr
  Opin Nephrol Hypertens. 20009477-487.
• Levey, A.S., Adler, S., Caggiula, A.W., England,
  B.K., Greene, T., Hunsicker, L.G., et al. (1996).
  Effects of dietary protein restriction on the
  progression of advanced renal disease in the
  Modification of Diet in Renal Disease study.
  American Journal of Kidney Disease, 27, 652-663.
• Lewis, E.J., Hunsicker, L.G., Clarke, W.R., Berl,
  T., Pohl, M.A., Lewis, J.B., et al. (2001).
  Renoprotective effect of the angiotensin-receptor
  antagonist irbesartan in patients with
  nephropathy due to type 2 diabetes. New England
  Journal of Medicine, 345, 851-860.
• Maroni, B.J. (2001). Strategies for improving
  nutrition in dialysis patients (abstract). Proc
  NKF, 142-143.
• McCarthy, J.T. (1999). A practical approach to
  the management of patients with chronic renal
  failure. Mayo Clin Proc, 74(3), 269-273.
• National Institutes of Health National Heart,
  Lung, and Blood Institute National High Blood
  Pressure Education Program. (1997). The Sixth
  Report of the Joint National Committee on
  Prevention, Detection, Evaluation, and Treatment
  of High Blood Pressure. Retrieved June 1, 2007,
  from http//www.ncbi.nlm.nih.gov/books/bookres.fcg
  i/hbp/hbp.pdf
• National Kidney Foundation. (2002). K/DOQI
  clinical practice guidelines for anemia of
  chronic kidney disease 2000. American Journal of
  Kidney Disease, 37, S182-S238. Retrieved June 6,
  2007, from http//www.kidney.org/professionals/kdo
  qi/guidelines_ckd/toc.htm

80
References

• Obrador, G.T., Pereira, B.J. (1998). Early
  referral to the nephrologist and timely
  initiation of renal replacement therapy A
  paradigm shift in the management of patients with
  renal failure. American Journal of Kidney
  Disease, 31(3), 398-417.
• Obrador, G.T., Ruthazer, R., Arora, P., Kausz,
  A.T., Pereira, B.J.G. (1999). Prevalence of and
  factors associated with suboptimal care before
  initiation of dialysis in the United States.
  Journal of the American Society of Nephrology,
  10, 1793-1800.
• Perazella, M.A., Eras, J. (2000). Are selective
  COX-2 inhibitors nephrotoxic? American Journal of
  Kidney Disease, 35, 937-940.
• Pereira B. (2000). Optimization of pre-ESRD care
  The key to improved dialysis outcomes. Kidney
  International, 57, 351-365.
• Rahman, M., Smith, M.C. (1998). Chronic renal
  insufficiency A diagnostic and therapeutic
  approach. Archives of Internal Medicine, 158,
  1743-1752.
• Russo, D., Pisani, A., Balletta, M.M., De Nicola,
  L., Savino, F.A., Andreucci, M., et al. (1999).
  Additive antiproteinuric effect of converting
  enzyme inhibitor and losartan in normotensive
  patients with IgA nephropathy. American Journal
  of Kidney Disease, 33, 851-856.
• Sarnak, M.J., Levey, A.S. (2000).
  Cardiovascular disease and chronic renal disease
  A new paradigm. American Journal of Kidney
  Disease, 35(Suppl 1), S117-S131.
• Sheinfeld, G.R., Bakris, G.L. (1999). Benefits
  of combination angiotensin-converting enzyme
  inhibitor and calcium antagonist therapy for
  diabetic patients. American Journal of
  Hypertension, 12, 80S-85S.

81
References

• Swan, S.K., Rudy, D.W., Lasseter, K.C., et al.
  (2000). Effect of cyclooxygenase-2 inhibition on
  renal function in elderly persons receiving a
  low-salt diet. Annals of Internal Medicine, 133,
  1-9.
• U.S. Department of Health and Human Services.
  (2000). Healthy People 2010 Chronic kidney
  disease. Retrieved June 1, 2007, from
  http//www.healthypeople.gov/document/html/volume1
  /04ckd.htm
• U.S. Renal Data System. (2008). USRDS 2008 annual
  data report. Bethesda, MD National Institutes of
  Health, National Institute of Diabetes and
  Digestive and Kidney Diseases. www.usrds.org
• U.S. Renal Data System. (2000). USRDS 2000 annual
  data report. Bethesda, MD National Institutes of
  Health, National Institute of Diabetes and
  Digestive and Kidney Diseases.
• U.S. Renal Data System. (1999). Chapter 5
  Patient mortality and survival. In USRDS 1999
  annual data report. Bethesda, MD National
  Institutes of Health, National Institute of
  Diabetes and Digestive and Kidney Diseases.
• Wolf, G. Ritz, E. (May 2003). Diabetic
  nephropathy in type 2 diabetes prevention and
  patient management. Journal of the American
  society of Nephrology, 14(5), 1396-405.
• Zabetakis, P.M., Nissenson, A.R. (2000).
  Complications of chronic renal insufficiency
  Beyond cardiovascular disease. American Journal
  of Kidney Disease, 36(Suppl 3), S31-S38.