Chronic Kidney Disease: A Silent Epidemic Part 1

1
Chronic Kidney Disease A Silent Epidemic (Part
1)

• Naima Ogletree, MSN, APRN, BC
• Nephrology Hypertension
• Henry Ford Health System

2
Objectives

• Define CKD prevalence, epidemiology, and risk
  factors
• Discuss occurrence of complications and co-morbid
  conditions of CKD
• Describe treatment guidelines

3
Kidney Anatomy

• Normal adult kidney is 1112 cm longWt 125170
  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

4
Physical Location of Human Kidney
LEFT KIDNEY
URETER
BLADDER
5
Anatomy of the Kidney
FIBROUS CAPSULE
CORTEX
PYRAMID
PAPILA
RENAL CALYX
RENAL PELVIS
RENAL ARTERY
RENAL VEIN
URETER
6
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

7
A MICROSCOPIC LOOK AT THE RENAL CORTEX
GLOMERULUS
8
Glomerulus Anatomy
9
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

10
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.

11
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

12
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. 200240S1S246.
13
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. 200240S1S246.
14
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

15
CKD Care is Costly
TH Hostetter, National Kidney Education Program,
2003.
16
CKD Prevalence by NHANES III
7.6
5.9
5.3
0.4
0.3
J Coresh, et al. Am J Kidney Dis. 200341(1)112
17
CKD Prevalence by NHANES III

• National Center for Health Statistics(19881994)
• Dataset (1988-1994) 15,625 adults
• Age 20 yr
• Extrapolated to 177 million adults
• CKD by SCr
• SCr 1.5 mg/dL, 6.2 million
• SCr 1.7 mg/dL, 2.5 million
• SCr 2.0 mg/dL, 0.8 million
• Greater SCr in older subjects, males
  andnon-Hispanic blacks

• HTN in 70
• 75 treated

CGM Jones, et al. Am J Kidney D.
199832992999. J Coresh, et al. Am J Kidney
Dis. 200341112.
18
CKD Prevalence by NHANES III
CGM Jones, et al. Am J Kidney Dis.
199832992999. J Coresh, et al. Am J Kidney
Dis. 200341112.
19
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. 200240S1S246.
20
ESRD Increasing Problem

• ? 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

Data on file National Kidney Foundation of
Michigan, 2002.
21
ESRD Disease of the Elderly
148,508
125,280
55,105
26,177
5961
n361,031
United States Renal Data System (USRDS) 1997
Annual Data Report.
22
ESRD ? Risk by EthnicityRacial Differences in
ESRD in U.S. from 19901998
United States Renal Data System (USRDS) 2000
Annual Data Report WWW.USRDS.ORG.
23
ESRD Prevalence by Ethnicity
Abbrev NA, Native American AA,
African-American C, Caucasian. n 361,031
United States Renal Data System (USRDS) 1997
Annual Data Report.
24
ESRD Incidence by Ethnicity Racial Differences
in ESRD in U.S. from 19901998
United States Renal Data System (USRDS). 2000
Annual Data Report WWW.USRDS.ORG.
25
ESRD ? Incidence and Prevalence
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.
26
ESRD Racial Distribution for Comorbidities in
Dialysis (1999)
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
27
Overall Rates of Hospitalization
Inpatient Days among Elderly Medicare Pts with
CKD in the United States.
Am J Kidney Dis. 2003 Nov42(5)972-81
28
GFR and Hospitalization
Go et al. New Engl J Med. 20043511296-1305.
29
Change in FOCUS
CKD
2
3
4
E S R D
30
CKD Becomes the Focus

• Rationale for Initiative
• CKD is a public health problem.
• Economical, effective testing methods and
  therapies exist.
• Testing and therapy are inadequately applied.

BA Boissonault. Niagara Health Quality Coalition,
2003. L Smith-Wheelock. National Kidney
Foundation of Michigan, 2003.
31
Timely Referral Keeps pts Out of the Red Zone
NKF CKD Stage by MDRD GFR Equation
4
5
E S R D
REFER TO KIDNEY DOCTOR

• Refer in Stage 1 or 2
• Uncontrolled HTN
• Hematuria
• Proteinuria
• Structural lesion

NORMAL AGE DECLINE
60
30
15
120
90
GFR (mL / min / 1.73 m2)
Kidney/Dialysis Outcomes Initiative. Am J Kidney
Dis. 200239S1S266.
32
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.
33
CKD ComplicationsEvolution and Acceleration by
Stage
DM, ARF CKD complications may occur earlier
34
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35
CKD Three-Fold Initiative

• Screen and prevent CKD in pts who are at-risk
• Develop an early CKD identification process
• Establish a collaborative disease management
  model for internists, family practitioners, and
  nephrologists

36
Detection 0f pts at Risk
BUN blood urea nitrogen GFR glomerular
filtration rate.Pereira. Personal communication.
37
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.
38
CKD High-Risk Groups

• Diabetics with urine AlbCr ratios30 mg Alb/1 g
  Cr
• Non-diabetics with urine AlbCr ratios 300 mg
  Alb/1 g Cr
• Non-diabetics with MDRD GFR

Kidney/Dialysis Outcomes Initiative. Am J Kidney
Dis. 200239S1S266.
39
CKD Screening and Prevention

• Screening at-risk pts
• Biochemical profile
• Urinalysis with microscopic exam
• Urine protein (albumin) determinations
• MDRD GFR estimation

40
CKD Three-Fold Initiative

• Screening of pts at-risk for CKD
• Development of an early CKD identification
  process
• Establishment of a disease management protocol
  between internists and family practitioners and
  nephrologists

41
CKD Evolution of GFR Estimating Methods
A Akbari, et al. Arch Intern Med.
2003163356360. S Klahr, et al. MDRD Study
Group. N Engl J Med. 1994330877884.
42
CKD MDRD GFR

• Multi-variable equation
• Demographics Age, Gender, Ethnicity
• Biochemical Albumin, SCr, BUN
• Validated in 577 pts
• By iothalamate clearance
• For GFRs 3090 mL/min/1.73 m2
• MDRD GFR Eqn. 7 (mL/min/1.73 m2) 170 ?
  SCr0.999 ? Age0.176 ? BUN0.17 ? Alb0.318 ?
  0.762 (female) ? 1.18 (African-American)

Kidney/Dialysis Outcomes Quality Initiative. Am J
Kidney Dis. 200239S1S266. G Manjunath, et al.
Postgrad Med. 2001110(6)5562.
43
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.
2001110(6)5562.
44
CKD NKF Definition

• Disorder must be 3 mo duration
• MDRD GFR
• 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)
• Dipstick ?2 or 100 mg/dL
• ProCr ratio ?1.0 (Pro and Cr in mg/dL)
• AlbCr ratio ?500 mg/g
• 24-h collection ?1.0 g/24-h/1.73 m2

S Klahr, et al. N Engl J Med. 1994330877. Kidney
/Dialysis Outcomes Quality Initiative. Am J
Kidney Dis. 200239S1S266.
45
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. 200239S1S266.
46
CKD Age-Related Decline in GFR

• Age-related declines in GFR occur
• Should not be considered disease
• GFR 6089 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. 200239S1S266.
47
NKF CKD Stages 15
Kidney/Dialysis Outcomes Initiative. Am J Kidney
Dis. 200239S1S266.
48
CKD Screening and Prevention Summary

• Use MDRD GFR not SCr
• Spot urine AlbCr ratio
• Collect specimen at 06001200 hours
• 24-h urine collection, no longer required
• Screenees?
• GFR
• 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.
2001110(6)5562.
49
CKD Three-Fold Initiative

• Screening for and prevention of CKD in pts
  at-risk for CKD
• Development of an early CKD identification
  process
• Establishment of a collaborative disease
  management model between internists and family
  practitioners and nephrologists

50
CKD Under-recognized Problem

• Patients unaware
• Only 13 of pts with CrCl 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. 20024011731178.
51
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. 199729368.
52
CKD Survey of PCPs
53
CKD Delayed Referral to Nephrologist
A Stack. Am J Kidney Dis. 200341310318.
54
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.
1998112417. DW Eadington. Nephron Dial
Transplant. 1996112124-2126. RJ Schmidt, et al.
Am J Kidney Dis. 199632278283. P Jungers, et
al. Kidney Int. 199341S170S173.
55
CKD Consequences of Delayed Referral
A Stack. Am J Kidney Dis. 200341310318. Late
referral means Nephrology consultation and dialysis. AVF,
arteriovenous fistula AVG, arteriovenous graft.
56
CKD Delayed Referral Results in Higher Medical
Costs in Early ESRD
Source BA Boissonault for the Niagara Health
Quality Coalition, 2003.
57
Advanced CKD Substantially Impairs Quality of Life
Klang et al. Quality of Life Research.
19965109-116.
58
Ultimate GoalDelay CKD Progression

• Diagnose / treat comorbid conditions
• Evaluate / treat CVD
• Iatrogenic risks _at_ CKD Stage 3
• protect against further insults (e.g., ARF)

59
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.
1997103368375 L Gruberg, et al. J Am Coll
Cardiol 20003615421548
60
CKD Increased Risk for ARF

• ECF volume depletion fosters ARF
• High-risk groups
• DM, types 1 and 2
• Non-DM CKD Stage 35 (i.e., GFR
• Liver failure
• Heart failure
• CV operations
• Radiocontrast procedures

E Nikolsky, et al. Rev Cardiovasc Med
20034(Suppl 1)S7S14. Data extrapolated from
multiple studies
61
Avoid Iatrogenic Injury

• AVOID NEPHROTOXINS
• NSAIDs, AGs, Amphotericin B
• Radiocontrast
• Stop diuretics 34 d before procedure
• ECF volume expansion(preferably with HCO3 ?)
• N-Acetylcysteine (SCr dependent)

M Tepel, et al. NEJM, 343180184, 2000 C Caputo,
et al. AJKD Dis 39A14, 2002 (abstract)
62
Acute Renal Failure NSAID-Induced Afferent
Arteriolar Constriction
NORMAL PGC
Paff
Peff
?PGC
? RAA
Paff
NSAID
Peff
VA Valentini, et al. Arch Intern Med.
199115123672372. RAA, afferent arteriolar
resistance.
63
NSAIDS

• NSAIDs (COX-1/-2 inhibitors) lower GFR, retain
  sodium and may cause hyperkalemia
• People with an activated Renin-Angiotensin-Aldoste
  rone system are especially at risk for
  NSAID-induced ARF
• Advanced age
• Hypertension
• Diabetes
• Dehydration
• Concomitant diuretic use

64
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 19943314161423.
NE Lepor. Rev Cardiovasc Med 20034(Suppl
1)S15S20.
65
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66
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. 1994331141620.
67
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 19943314161423 N
E Lepor. Rev Cardiovasc Med 20034(Suppl
1)S15S20
68
Recommendations for Common Interventions Used to
Prevent Contrast-medium-induced Nephropathy
69
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. 20032(3)85111.
70
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

71
CKD Guidelines for Treatment

• National Kidney Foundations Kidney Disease
  Outcomes Quality Initiative (NKF KDOQI)
• Based heavily on Evidenced Based Medicine
• Offers opinions that guide treatment

72
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73
NKF Guidelines address domains of CKD care
74
NKF Guidelines address domains of CKD care
Periodic eGFR
75
Decrease CV Disease Risk Factors
76
CKD CVD Prevention Strategies Level of
Evidence
Large RCTs that involve CV risk prevention
strategies in CKD have not been performed.
77
Major Cause of Death in CKDCardiovascular Disease
Shulman et al. Hypertension. 199813(supple
1)I-80I-93.
78
CKD CVD Risks

• CVD risk ? 1.42.05X ifSCr 1.41.5 mg/dL
• CVD risk ? 1.53.5X with microalbuminuria
• First-year CVD mortality of CKD (3.5) increases
  5-fold (17) with addition of diabetes
• Annual CVD ?10100X 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.
79
Cardiovascular Health Study Even Mildly
Elevated SCr Increases CV Disease (CVD) Risk.
Kidney/Dialysis Outcomes Initiative Clinical
Practice Guidelines for Managing Dyslipidemias in
Chronic Kidney Disease. Am J Kidney Dis.
200341(Suppl 3)S1S91.
80
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.
81
CV Mortality in General Population (GP)
Dialysis pts by Ethnicity
MJ Sarnak, AS Levey. Semin Dial. 1999126976.
82
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.
200341(Suppl 3)S1S91.
83
Decrease CV Risk Factors

• Strict BP control
• Tight glycemic control
• Use anti-RAAS drugs
• Lipid control
• Correct anemia

84
Hypertension CKD
85
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).

86
BP Control is Suboptimal
SBP NHLBI. JNC 7 Express. The Seventh Report of the
Joint National Committee on Prevention,
Detection, Evaluation and Treatment of High Blood
Pressure. 2003.
87
JNC 7 Reclassification of BP Based on Risk
JNC VIBP (mm Hg)
JNC 7BP (mm Hg)
Optimal
Normal
Normal
120-129/80-84
Prehypertension
120-139/80-89
Borderline
130-139/85-89
Hypertension
Stage 1
140-159/90-99
Stage 1
140-159/90-99
Stage 2
160-179/100-109
Stage 2
160/100
Stage 3
180/110
Source for JNC VI Arch Intern Med.
19971572413-2446. Adapted from Chobanian AV, et
al. Hypertension. 2003421206-1252.
88
HTN Treatment by JNC 7
HTN w/ No Compelling Indications
C(KD)ompelling Indications
Stage 1 HTN (SBP 140-159 or DBP 9099
mmHg) Thiazidediuretic for most Consider ACEI,
ARB, ß-blocker, CCB or combination
Stage 2 HTN (SBP 160 or DBP 100 mmHg) 2-drug
combofor most Usually thiazide ACEI, ARB,
ß-blocker, or CCB
Drug(s) for compelling indications Other BP drugs
(thiazide ACEI, ARB, ß-blocker, CCB)as needed
Chobanian AV, et al. The JNC 7 Report. JAMA.
20032892560-2572. Compelling indications CHF,
post-MI, high risk of CAD, DM, CKD, stroke,
migraine
89
BP Targets in Diabetic and Nondiabetics with
Kidney Disease
Am J Kidney Dis, May (Suppl.), 2004
90
HTN Treatment in CKDDiabetic or Nondiabetic
91
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
• 1 g/d

92
BP Control Prevents CKD Progression
MAP (mm Hg)
95
98
101
107
104
110
113
116
119
r0.69 PGFR Decline(mL/min/y)
Untreated HTN
130/85
140/90
GFR, glomerular filtration rate HTN,
hypertension MAP, mean arterial
pressure. Adapted from Bakris GL et al. Am J
Kidney Dis. 200036646-661.
93
Hypertension CKDOptimal 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
• RAAS blockade
• ACEI
• ARB

94
Benefits of BP TherapyGeneral Population
CAD coronary artery disease, PAD peripheral
artery disease CHF congestive heart
failure. Adapted from Kannel WB. JAMA.
19962751571-1576.
95
Hypertension and CKDMultiple Drugs Required
UKPDS (Type 2 DM
MDRD (Nondiabetic Kidney Disease
HOT (DM Subgroup Analysis
AASK (African Americans, No DM
RENAAL (Type 2 DM Nephropathy
IDNT (?135/85 mm Hg)
Type 2 DM Nephropathy
4
3
2
1
Number of BP Medications
MAP mean arterial pressure.
Bakris G, et al. AJKD. 200036646-661 Brenner
BM, et al. NEJM. 2001345861-869. Lewis EJ, et
al. NEJM. 2001345851-860.
96
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97
Glycemic Control
98
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 in25 of pts per
  year

98
99
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

100
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101
Global Estimates and Projectionsfor Incidence of
Diabetes Mellitus
Type I Diabetes
Type II Diabetes
250
200
150
In Millions
100
50
0
1997
2010
Year
A Amos, et al. Diabetes Medicine. 199714Suppl
5S1-85.
102
NEW ESRD Incidence from DM
Centers for Disease Control Diabetes
Surveillance, 1997.
103
Predictions Regarding T2DM

• 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
• Year 2050
• U.S. 45?50 million will develop T2DM
• Implications for CKD and RRT uncertain

Dr. KM Venkat Narayan
104
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 long-term complications of diabetes
develop.
New Engl J Med 2002346(11)
105
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.
106
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 19992000 cohort.
107
Natural History of Diabetic Nephropathy
108
Glomerulus Site of Hyperfiltration in Diabetes
and Obesity
109
(No Transcript)
110
Diabetic Glomerulosclerosis
111
Glycemic Control Retards Progression of CKD
50 Reduction
Based on Diabetic Control and Complications
Trial data
Adapted with permission from Skyler JS.
Endocrinol Metab Clin North Am. 199625243
112
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
113
HbA1c Delay DN
Glycemic Control
114
HbA1c Delay DN

• REQUIREMENTS
• HbA1C 6.5
• FBS 110 mg/dl
• 2-h PPG 180 mg/dl

Glycemic Control
115
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 3396975, 1998
116
HbA1c Delay DN
DCCT Research Group. New Engl J Med 329977, 1993
117
(No Transcript)
118
Decline of GFR in DN
119
Questions?
120
Chronic Kidney Disease A Silent Epidemic (Part
2)

• Naima Ogletree, MSN, APRN, BC
• Nephrology Hypertension
• Henry Ford Health System

121
Proteinuria Reduction
122
CKD Albuminuria
G Remuzzi, et al. New Engl J Med. 2002
34611451150.
123
ProteinuriaDual 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

124
RAAS, Albuminuria and AtherosclerosisSteno
Hypothesis
American Journal of Kidney Diseases, Vol 47, No 6
(June), 2006 pp 927-946
125
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
14641647. MARVAL Circulation.
2002106672-678. RENAAL N Engl J Med.
2001345861869. IDNT N Engl J Med.
2001345851860.
126
Albuminuria Decreases SurvivalGraded Effect
Gall MA, et al. Diabetes 1995441303-1309
127
UPC _at_ 6 Mo Predicts Kidney CVD Events RENAAL
Substudy (losartan, no ACEI)
RENAAL Study Group, 2002
128
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

129
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
130
How RAAS Blockade is Beneficial
Adapted from Hall JE et al. J Am Soc Nephrol.
199910S258-S265. A Chagnac, et al. Glomerular
hemodynamics in severe obesity. Am J Physiol
2000278F817-F822.
131
ACEIs / ARBs

• Clinicians often avoid / withdraw ACEIs / ARBs in
  CKD fearing hyperkalemia or ? SCr
• Tolerate
• up to 30 increases of SCr
• K of 5.55.8 mEq/L
• Kidney dietitian, not Kayexelate

FF Hou, et al. NEJM, 2006.
132
Alternative to RAAS Blockers

• Non-dihydropyridine CCBs for those who cannot
  tolerate anti-RAAS agents, especially with
  proteinuria
• Diltiazem
• Verapamil

133
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 14641647.MARVAL. Author. Circulation
2002106672-678. RENAAL. BM Brenner, et al. N
Engl J Med 2001345861869. IDNT. EJ Lewis, et
al. N Engl J Med345851860.
134
RENAAL Combined CCB and ARB Reduce Progression
to Diabetic Nephropathy
NORMAL PGC
Paff
Peff
?RAA
?REA
NORMAL PGC
Paff
Peff
ACEI (type 1 DM) ARB (type 2 DM)
CCB
Adapted from RENAAL Study. BM Brenner, et al. N
Engl J Med. 2001345861869. RAA, afferent
arteriolar resistance. REA, efferent arteriolar
resistance.
135
IRMA 2 ARB Prevents Transition from Micro- to
Macroalbuminuria
H-H Parving, et al. New Engl J Med.
2001345870878.
136
IRMA 2 ARB Prevents Transition from Micro- to
Macroalbuminuria
H-H Parving, et al. New Engl J Med.
2001345870878.
137
IRMA 2 ARB Normalizes Albumin Excretion Rate
P H-H Parving, et al. New Engl J Med. 2001870878.
138
Effect of AngII Receptor Blockade in Type 2
Diabetic Nephropathy
BM Brenner, et al. N Engl J Med 2001345861869.
139
Irbesartan Diabetic Nephropathy Trial
EJ Lewis, et al. N Engl J Med. 2001345851860.
140
Reduction in Endpoints in Non-Insulin Dependent
DM with the Angiotensin II Antagonist Losartan
BM Brenner, et al. N Engl J Med 2001345861869.
141
Diabetes and RAAS BlockadeType 2 DM

• Brenner et al. (losartan, RENAAL) (N1513)
• Lewis et al. (irbesartan, IDNT) (N1715)
• ARBs reduced proteinuria (35)
• reduce rate of GFR decline
• later onset of ESRD compared to placebo
• Mean delay of ESRD by 2.3 yr

142
Lipid Control
143
Guideline Lipids in CKD 14

• 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 23 MO
  after a change in treatment or other conditions
  known to cause dyslipidemias and at least
  annually thereafter. (B)

144
Dyslipidemia CKDTreatment Protocol
Lifestyle Modification Always
145
Dyslipidemia CKDTreatment Protocol
Lifestyle Modification Always
146
Treatment of Dyslipidemia Therapeutic Targets

• CKD pts are considered the highest CV risk
  population
• Primary Target LDL-C reduction to
• Secondary Target TG reduction to non-HDL-C reduction to
• Constant reinforcement of therapeutic lifestyle
  changes

147
CKD Dyslipidemia Treatment

• Smoking cessation
• Aspirin use
• Wt loss
• Aerobic Exercise
• Statins
• Fibric Acid Derivatives
• LDL Goal 40mg/dL, TG 150mg/dL, Non-HDL-C

K/DOQI Clinical Practice Guidelines for Managing
Dyslipidemias in Chronic Kidney Disease. Am J
Kidney Dis 200341(Suppl 3)S1S91.
148
CKD Lipid Therapy

• Rationale for Intervention
• CKD progresses faster in dyslipidemia
• Physicians Health Study (19821996)
• N4,483 initially healthy males
• 14-Yr followup
• Baseline SCr
• HDL 40 mg/dL 50 ? risk of reduced GFR
• Non-HDL-C 196 mg/dL 100 ? risk of reduced GFR

T Kurth, et al. J Am Soc Nephrol
20031420842091.
149
CKD Lipid Targets
Kidney/Dialysis Outcomes Initiative Clinical
Practice Guidelines for Managing Dyslipidemias in
Chronic Kidney Disease. Am J Kidney Dis
200341(Suppl 3)S1S91.
150
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. 200341(Suppl 3)S1S91.
151
Lipid TargetsTotal Cholesterol 200

• LDL-C
• TG
• Non-HDL-C

http//www.kidney.org/PROFESSIONALS/kdoqi/guidelin
es_lipids/ii.htmguide3
152
Anemia of CKD
153
(No Transcript)
154
CKD Anemia Induces LVH
Excerpt H Hampl, L Henning and E Riedel.
Dialysis Times 20039(5)16 A Mohanran and AS
Kliger presentations at NKF Meeting 2003
155
(No Transcript)
156
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.

157
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
20039(5)16. Presentations A Mohanran and AS
Kliger. National Kidney Foundation Annual
Meeting, 2003.
158
CKD Anemia ? as GFR ?
Adapted from Radtke, et al. Blood.
197954877884 (original study used Hct).
159
RBC Production Response in CKD
6X
5X
Normal
4X
RBC Production (mL/Day)
3X
CKD
2X
1X
0
0.1
1.0
10
102
103
104
EPO Concentration (mU/mL)
160
EPO Response Blunted as CKD Progresses
Hemoglobin (g/dL)
EPO level (mU/mL)
15
14
13
12
11
10
9
8
7
6
59
29
18
18
34
18
N
5
100-70
70-40
40-25
25-15
15-10
Percent of Normal Kidney Function
Radtke HW. et al Blood 197954877 Erslev AJ. N
Engl J Med 19913241339
161
Anemia A Risk Multiplier
Source Medicare sample (5), followup from 1996
to 1997 of enrollees aged 65 y.o., adjusted for
age, gender and race.
162
QoL Improves with Higher Hb

• Cognitive function
• Energy/activity
• Sleep and eating behavior
• Satisfaction with health
• Well-being
• Satisfaction

• Exercise capacity
• Functional ability
• Health Status
• Sex Life
• Psychological effect
• Happiness

163
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 1S1-S3, 2006

164
IV Iron May Have an Independent Erythropoietic
Effect in HD
39 new HD pts (no EPO therapy) with baseline
iron deficiency by bone marrow aspiration.
P 199879299305.
165
More Rapid Hgb Response With EPO IV Iron
Defined as 0.5-g/dL increase in Hgb. Panesar et
al. Am J Kidney Dis. 200240924-931.
166
Available Oral Iron Preparations
167
Currently Available Erythropoietic Agents

• First generation erythropoietic agents
• Epoetin alfa (Amgen Epogen , JJ 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

168
CKD Anemia Therapy

• Begin tx at Hb
• Steps (by Nephrology CKD Clinic)
• Replete iron stores
• Oral iron salts
• Iron dextran (INFeD?) or Iron gluconate
  (Ferrlecit?) or Iron sucrose (Venofer?)
• Use erythropoietic agent
• Epoetin-a (Procrit?) or
• Darbepoetin (Aranesp?)

J Yee, A Besarab. Am J Kidney Dis
20024011111121
169
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
19991020292043 AR Nissenson. Am J Kidney Dis
20013813901397
170
Chronic Kidney DiseaseMineral and Bone Disorder
171
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
172
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
173
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
174
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.
1995333(3)166-174. DJ Sherrard, et al. Kidney
Int. 199343(2)436442.
175
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 non-ESRD CKD).
• ESRD pts develop CV calcification (by EBCT) from
  ? Ca P product.

WG Goodman, et al. New Engl J Med.
2000342(20)14781483.
176
CKD Pathophysiology of 2 HPT
177
Progression of PTH Gland Hyperplasia in CKD
VDR vitamin D receptor CaR Ca-Sensing
receptor. Adapted from Murayama A et al.
Endocrinology. 19991402224-2231. Satomura K et
al. Kidney Int. 198834712716
178
CKD Renal Osteodystrophy Ca / P / PTH Axis
KG Koenig, et al. Kidney Int. 199141161165.
179
CKD ROD PTH Target
150
300
K/DOQI PTHTarget (pg/mL)
100
500
Low bone turnover Adynamic bone disease
High bone turnover Bone pain Cardiovascular
disease Cognitive impairment
180
CKD ROD Ca Target
9.5
8.4
K/DOQI Target Ca(mg/dL)
10.2
7.5
Stimulus for PTH secretion Stimulus for PT
gland enlargement Inadequate skeletal
mineralization
Vascular/soft tissue calcification
Hypertension
181
CKD ROD P Target
Malnutrition Inadequate bone mineralization
Vascular/soft tissue calcification
Cardiovascular disease Higher mortality risk
182
CKD Renal Osteodystrophy

• Targets
• Ca 8.49.5 mg/dL
• P 2.75.5 mg/dL
• Ca P
• HCO3 2226 mEq/dL
• PTH

Draft Kidney/Dialysis Outcomes Initiative
Clinical Practice Guidelines for Bone Metabolism
and Disease. National Kidney Foundation Task
Force, 2003
183
CKD Renal Osteodystrophy ? P ? Relative Risk
of Mortality
GA Block, et al. Am J Kidney Dis 199831607617.
184
Mortality Risk in ESRDby Serum P and Ca Levels
RR relative risk Not adjusted for active
vitamin D intake Block et al. J Am Soc Nephrol.
2004152208-2218.
185
Prevalence of Calcitriol Deficiency and Anemia in
pts With CKD by eGFR

• Design
• N 80 CDK
• Anemia defined as Hb ESA
• Calcitriol deficiency defined as calcitriol pg/mL
• Results
• Prevalence of calcitriol deficiency was greater
  than prevalence of anemia at all stages of CKD

Gutierrez et al. J Am Soc Nephrol
2005162205-2215.
186
SHPT Occurs Early in CKD
N150
Martinez et al. NDT 19961122-28.
187
CKD-Mineral Bone DisorderCa/P/PTH Progression
in CKD
P 100 and CrCl 50-59,
N 157
Martinez I, et al. Am J Kidney Dis.
199729496-502.
188
Recommendations for Early Monitoring of PTH, Ca,
and P Metabolism in CKD
GFR in mL/min/1.73 m2 KDOQI Guidelines for Bone
Metabolism and Disease. Am J Kidney Dis.
200342(4 suppl 3)S1-S201.
189
Vitamin D in CKD Stages 3 and 4

• Stages 3 and 4 Measure serum 25(OH) D in pts
  with ? PTH.If normal, repeat q12 mo.

Normal 25(OH)D ?30 ng/mL Insufficiency

NKF. Am J Kidney Dis. 200342(4 suppl 3)S1-S201.
190
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 0.81.0 g/d if P 5.5 mg/dL
• Restrict P to 0.81.0 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
191
High-Turnover Bone Disease Can Result in
Soft-Tissue Calcification
192
Low-Turnover Bone Disease Can Result in
Soft-Tissue Calcification
193
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
194
CKD Renal Osteodystrophy Tx

• Non-Ca-based binders
• Avoid aluminum-based gels
• Sevelamer hydrochloride (Renagel)
• Use in CKD Stages 3 and 4
• 800 mg capsules 12 tid with meals
• 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
195
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 0.51.0 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.
197556(2)414419.
196
Acidosis Aggravates Renal Osteodystrophy
197
Acidosis Treatment

• May occur earlier in diabetic CKD, compared to
  non-diabetic CKD
• Type IV RTA
• Treatment same in diabetic and non-diabetic CKD
• HCO3 22 mEq/L
• NaHCO3 tablets (0.51.0 mEq/kg/day)

Verify acidemia with ABG
198
Nutritional Assessment
199
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.

200
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

201
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.

202
Intervention

• Caloric restriction
• 25 cal/kg of SBW to lose wt
• 30 cal/kg of SBW to maintain wt
• 3540 cal/kg of SBW to gain wt
• Fluid restriction
• implement only if Nacompliant with low Na diet.
• may be temporary

203
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 1994330877884. EL
Knight, et al. Ann Intern Med 2003138460467.
204
CKD Nutrition ? Protein Intake Associated with
? Kidney Function

• Nurses Health Study (n1135 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. 1994330877884 EL Knight, et al. Ann
Intern Med 2003138460467.
205
CKD Nutrition Therapy

• Consult Renal Dietitian at CKD Stage 3
• Protein restrict _at_ GFR
• High biologic protein 0.60.75 g/kg bw
• Initiate dialysis if
• GFR protein intake
• 6 wt loss or

Kidney/Dialysis Quality Outcomes Initiative
Clinical Practice Guidelines for Managing
Dyslipidemias in Chronic Kidney Disease. Am J
Kidney Dis 200341(Suppl 3)S1S91.
206
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
  to8001000 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. 200342(4 suppl 3)S1-S201.
207
Vaccinations
208
Vaccinations

• CKD pts immunocompromised
• Despite immunodeficiency, CKD pt immunized less
  frequently against flu and S pneumoniae than
  general medical pts

209
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

210
Influenza Vax rates Below National Target
(Healthy People 2000)
Gilbertson et al, Kidney Int 2003 63738-743
MMWR 2001, 50532-37
211
Odds of Hospitalization Death are Reduced In
Vaccinated HD pts
_________________ __________________________
Hospitalization Death
Gilbertson et al, Kidney Int 2003 63738-743
212
Evaluate Progression of CKD
213
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.

214
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.

215
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

216
DIALYSIS Arteriovenous Fistula

• Surgically connect endogenous artery to
  endogenous vein (no Gortex, AVG)
• Safest and longest half-life of all accesses
• Least expenive

217
AV