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Chronic Kidney Disease: A Silent Epidemic (Part 1)

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Title: 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 gt Right kidney in size,male gt
    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 gt20 yr
  • Extrapolated to 177 million adults
  • CKD by SCr
  • SCr gt1.5 mg/dL, 6.2 million
  • SCr gt1.7 mg/dL, 2.5 million
  • SCr gt2.0 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
  1. Screen and prevent CKD in pts who are at-risk
  2. Develop an early CKD identification process
  3. Establish a collaborative disease management
    model for internists, family practitioners, and
    nephrologists

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 ratiosgt30 mg Alb/1 g
    Cr
  • Non-diabetics with urine AlbCr ratios gt300 mg
    Alb/1 g Cr
  • Non-diabetics with MDRD GFRlt60 mL/min/1.73 m2

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 gt3 mo duration
  • MDRD GFR lt90 mL/min/1.73 m2 or
  • GFR gt90 mL/min/1.73 m2 with either
  • Parenchymal abnormality (cyst, scar) or
  • Hematuria (gt4 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 gt90 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 lt90 mL/min/1.73 m2
  • Not from age-related decline
  • Hypertension
  • Diabetes annual testing
  • FH of CKD less frequently, if normal
  • Hematuria
  • Edema of unknown cause

G Manjunath, et al. Postgrad Med.
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 lt60 mL/min or 1
    dipstick proteinuria aware of their CKD
  • Only 8 of pts with known CKD aware of their
    CKD, despite recent physician visit
  • Implications
  • Physicians require more CKD knowledge
  • Late referral of pts with advanced CKD to
    nephrologists, e.g., African-American men

Am J Kidney Dis. 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 lt4 mo between time of initial
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 lt60)
  • 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
IV saline therapy 0.9 saline at 1 mL/kg/h for 24 h, start 12 h pre-contrast delivery Small randomized trials iv saline vs oral fluids shorter regimens of iv fluids and 0.45 saline Optimal duration of iv therapy not fully established by existing trials RECOMMENDED Avoid ECF volume depletion Optimize HF 125 mL/h NSS
Contrast Medium Low osmolality, lowest dose possible Meta-analysis of many RCTs comparing low to high Isosmolar contrast may be less risky in high risk pts, more data required Low osmolality medium Lowest contrast volume
IV Sodium Bicarbonate 154 mmol/L at 3 cc/kg/h before contrast, then 1 mL/kg/h for 6 hours after Single RCT showed lower risk of 25 increase of SCr v 0.9 saline at same rate/duration Methodologic flaws in trial Not generally recommended, need further trials to confirm efficacy
N-acetyl cysteine 600 mg poq12 h 4, starting before contrast delivery Multiple RCTs Meta-analyses Inconsistent trial results, optimal dose not clear Recent high-dose study shows benefit in angioplasty
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 gt1.41.5 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
National Health and Nutrition Examination Surveys (Weighted ) National Health and Nutrition Examination Surveys (Weighted ) National Health and Nutrition Examination Surveys (Weighted ) National Health and Nutrition Examination Surveys (Weighted ) National Health and Nutrition Examination Surveys (Weighted )
II (19761980) III Phase 1 (19881991) III Phase 2 (19911994) 19992000
Awareness 51 73 68 70
Treatment 31 55 54 59
Control 10 29 27 34
SBP lt140 mmHg and DBP lt90 mmHg
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
lt120/80
Normal
lt120/80
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
Type of Kidney Disease BP Target (mm Hg) Preferred Agents for CKD, with or without HTN Other Agents to Reduce CVD Risk and Reach BP Target
Diabetic CKD SBP lt125130 DBP lt7580 ACE inhibitor or ARB Diuretic preferred, then BB or CCB
Nondiabetic CKD UPC ?200 mg/g SBP lt125130 DBP lt7580 ACE inhibitor or ARB Diuretic preferred, then BB or CCB
Nondiabetic CKD UPC lt200 mg/g SBP lt125130 DBP lt7580 None preferred Diuretic preferred, then ACEI/ARB,BB or CCB
CKD in TX Recipient SBP lt125130 DBP lt7580 None preferred CCB, diuretic, BB, ACE inhibitor, ARB
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 gt4 ml/min/1.73 m2/yr
  • Target BP
  • lt130/80 mmHg if proteinuria lt1 g/d
  • lt125/75 mmHg if proteinuria gt1 g/d

92
BP Control Prevents CKD Progression
MAP (mm Hg)
95
98
101
107
104
110
113
116
119
r0.69 Plt.05
GFR 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 gt40 ml/min/1.73 m2, HCTZ
  • GFR lt40 ml/min/1.73 m2, loop agent
  • 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 (lt85 mm Hg, diastolic)
Type 2 DM
MDRD (lt92 mm Hg, MAP)
Nondiabetic Kidney Disease
HOT (lt80 mm Hg, diastolic)
DM Subgroup Analysis
AASK (lt92 mm Hg, MAP)
African Americans, No DM
RENAAL (lt140/90 mm Hg)
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
(No Transcript)
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
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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
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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 lt0.05
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 lt70-100 mg/dL
  • Secondary Target TG reduction to lt150 mg/dL,
    non-HDL-C reduction to
  • lt130 mg/dL
  • Constant reinforcement of therapeutic lifestyle
    changes

147
CKD Dyslipidemia Treatment
  • Smoking cessation
  • Aspirin use
  • Wt loss
  • Aerobic Exercise
  • Statins
  • Fibric Acid Derivatives
  • LDL Goal lt 100mg/dL, HDL gt 40mg/dL, TG lt
    150mg/dL, Non-HDL-C lt 130mg/dL

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 lt1.5 mg/dL
  • HDL gt40 mg/dL 50 ? risk of reduced GFR
  • Non-HDL-C gt196 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
  1. LDL-C lt100 mg/dL (Optimal 70 mg/dL)
  2. TG lt150 mg/dL
  3. Non-HDL-C lt130

http//www.kidney.org/PROFESSIONALS/kdoqi/guidelin
es_lipids/ii.htmguide3
152
Anemia of CKD
153
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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 gt 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 gt 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
lt10
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 gt65 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 lt0.01 vs baseline. Fudin et al. Nephron.
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
Strength (mg/tablet) Elemental Fe (mg/tablet) No. Tablets to Supply 200 mg Elemental Fe
Ferrous sulfate 325 65 3
Ferrous gluconate 325 38 5
Ferrous fumarate 200 66 3
Iron poly-saccharide 150 150 2
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 lt11 g/dL (Hct 33)
  • 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 gt11 g/dL (Hct 33)
  • TSAT gt20 Ferritin gt100 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 lt55 mg2/dL2
  • HCO3 2226 mEq/dL
  • PTH lt23 ULN (100150 pg/mL)

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 lt11 g/dL or treatment with
    ESA
  • Calcitriol deficiency defined as calcitriol lt30
    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 lt 0.05,compared to CrCl gt 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
CKDStage GFR Range Measure PTH Measure Ca P
3 3059 12 MO 12 MO
4 1529 3 MO 3 MO
5 lt15 or ESRD 3 MO 1 MO
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
lt25 Deficiency lt15 ng/mL
Level Treatment with Vitamin D2 (Ergocalciferol, 50,000 IU capsules)
lt5 ng/mL 50,000 IU/wk x 12, then q MO x 6
515 ng/mL 50,000 IU/wk x 4, then q MO x 6
1629 ng/mL 50,000 IU/MO x 6
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 gt10.2 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 gt5.5 mg/dL
  • Switch to non-Ca-containing P-binders (sevelamer)
  • Restrict P to 0.81.0 g/d if P gt5.5 mg/dL
  • Restrict P to 0.81.0 g/d if PTH gt50 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 gt 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 Nalt132 mEq/L and pt is
    compliant 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 gt38 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 lt25 mL/min/1.73 m2
  • High biologic protein 0.60.75 g/kg bw
  • Initiate dialysis if
  • GFR lt1520 with energy malnutrition from low
    protein intake
  • 6 wt loss or lt90 of IBW in lt6 mo

Kidney/Dialysis Quality Outcomes Initiative
C
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