Clinical Practice Guideline for the Diagnosis, Evaluation, Prevention, and Treatment of Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD)

1
Clinical Practice Guideline for the Diagnosis,
Evaluation, Prevention, andTreatment of Chronic
Kidney Disease-Mineral and Bone Disorder (CKD-MBD)
Linda McCann, RD, CSR,LD Senior Director of
Quality Satellite Healthcare, Inc. Mountain View,
CA
2
History of Treatment Strategies forSecondary
Hyperparathyroidism
1970 1980 1990 2000
2010
Focus Bone Disease, Systemic effects of
PTH, High Ca was thought to be good
Focus Fractures, Mortality, Vascular
Calcification
3
KDIGO CKD-MBD Guidelines Work Group Members

• Sharon M. Moe, MD (Co-chair)
• United States
• Alison MacLeod, MD
• United Kingdom
• Linda McCann, RD, LD, CSR
• United States
• Peter A McCullough, MD, MPH
• United States
• Susan Ott, MD
• United States
• Angela Yee-Moon Wang, MD, PhD
• Hong Kong
• José Weisinger, MD
• Venezuela
• David Wheeler, MD
• United Kingdom

• Tilman Drüeke, MD (Co-chair)
• France
• Geoffrey Block, MD
• United States
• Jorge B. Cannata-Andía, MD, PhD
• Spain
• Grahame Elder, MB, BS, PhD
• Australia
• Masafumi Fukagawa, MD, PhD
• Japan
• Vanda Jorgetti, MD, PhD
• Brazil
• Markus Ketteler, MD
• Germany
• Craig Langman, MD
• United States
• Adeera Levin, MD,
• Canada

KDIGO. Kid Int. 2009 76 (Suppl 113)S1-S130
4
Chronic Kidney Disease Mineral Bone
Disorder (CKD MBD)

• A systemic disorder of bone and mineral
  metabolism due to CKD manifested by either one or
  a combination of the following
• Abnormalities of calcium, phosphorus, PTH, or
  vitamin D metabolism
• Vascular or other soft tissue calcification
• Abnormalities in bone turnover, mineralization,
  volume, linear growth, or strength

Moe et al. Kidney Int 2006691945-1953
5
Classification of Renal Osteodystrophy
T M V
Mineralization Reflects how well bone collagen
becomes calcified Normal-Abnormal
Volume Amount of bone per unit volume of tissue,
affected by , endocrine disorders, mechanical
stimuli, toxicities, neurological function,
vascular supply, growth factors and cytokines.
High-Normal-Low
Turnover Rate of remodelling High-Normal-Low
Slide courtesy of Susan Ott
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Process
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Grading the Evidence
Guyatt, et al, BMJ 2008
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NOMENCLATURE AND DESCRIPTION FOR RATING GUIDELINE
RECOMMENDATIONS
Grade Implications Implications Implications
Grade Patients Clinicians Policy
Level 1 We recommend Most people in your situation would want the recommended course of action and only a small proportion would not. Most patients should receive the recommended course of action. The recommendation can be adopted as a policy in most situations.
Level 2 We suggest The majority of people in your situation would want the recommended course of action, but many would not. Different choices will be appropriate for different patients. Each patient needs help to arrive at a management decision consistent with her or his values and preferences. The recommendation is likely to require debate and involvement of stakeholders before policy can be determined.

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Determinants of strength of recommendation
Guyatt, et al, BMJ 2008
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KDIGO Grading of Recommendations
Strength of Recommendation Implications
Level 1 We recommend Most patients should receive the recommended course of action.
Level 2 We suggest Different choices will be appropriate for different patients.
Grade for Quality of Evidence Quality of Evidence
A High
B Moderate
C Low
D Very Low
Not Graded
The strength of a recommendation is determined
not just by the quality of evidence, but also by
other, often complex judgments regarding the
size of the net medical benefit, values and
preferences, and costs.
KDIGO. Kid Int. 2009 76 (Suppl 113)S1-S130
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Sequential Process for Guideline Development

• First Steps
• Develop questions and define outcomes
• Preparatory Steps
• Conduct systematic review of literature
• Prepare evidence profile for important outcomes
• Grading
• Grade quality of the evidence
• Rank relative importance of each outcome
• Grade overall quality of evidence across all
  outcomes
• Assess balance of benefits and harms
• Forumlate recommendation and grade strength
• Subsequent Steps
• Implement and evaluate

GRADE BMJ 2005
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Evidence Model for CKD-MBD
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Interpreting a surrogate outcome trial
Clinical outcome trial - different drug class
(Phosphate Binder C)
Surrogate Outcome Trial (Phosphate Binder A)
Clinical outcome trial in same drug class
(Phosphate Binder B)
Observational Association
Intervention Treatment with Phos Binder
Intervention Treatment with Phos Binder
Intervention Treatment with Phos Binder A
Surrogate Outcome Slowing of Calcification
Surrogate Outcome Less Calcification
Surrogate Outcome Slowing of Calcification
Surrogate Outcome Slowing of Calcification
Clinical Outcome Less CVD Risk
Clinical Outcome Less CVD Events
Clinical Outcome Less CVD Events
Is there a strong, independent , consistent
association between the surrogate outcome and
clinical outcome? (Necessary but not sufficient
on its own) Is there evidence from RCTs in same
drug class that improvement of the surrogate
outcome consistently leads to improvement of
clinical outcome? Is there evidence from RCTs in
other drug classes that improvement in surrogate
outcomes has consistently lead to improvement in
clinical outcomes? (Last two should apply )
Illustration of principles outlined in Users
Guide for a Surrogate End Point Trial Bucher et
al. JAMA 1999, 282 (8) 771-778
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Extensive Guideline Review Process

• KDIGO Executive Committee and Board
• Represenatives of Five International Guideline
  Development groups
• Organizational, Stakeholder, and Public Review
• All comments submitted at each phase of review
  process were carefully reviewed and considered by
  the work groups prior to publication of final
  guidelines.

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Key Categories in KDIGO
Diagnosis/Evaluation
Vascular Calcification
Treatment
16
Prevalance of types of bone disease as determined
by bone biopsy.
These pie charts represent the prevalence of
various types of bone disease in CKD. Differences
are due to inconsistent classification methods,
geographic areas, genetic background, and
treatment strategies. One of the most
problematic classification differences relates to
the bone formation which requires tetracycline
labeling, hindered because normal ranges cannot
be determined on autopsy or surgical series
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KDIGO Diagnosis of CKD-MBDBiochemical
Abnormalities
Diagnosis of CKD-MBD depends primarily on lab and
other measures interpretation of biochemical and
hormonal values requires that there be an
understanding of the assay type and precision,
interassay variability, blood sample handling,
normal postprandial, diurnal, and seasonal
variations in the individual parameters.
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Sources and magnitude of variation in measures of
Ca, P, PTH, and D sterols
Variable Ca P PTH Vit D Sterol
Coefficient of of variation (Min/low)
Diurnal (Mod) No variability
Seasonal Not tested Not tested Not tested
Meals No variability
Dialysis Time Not tested Not tested
Assay validity (High)

• Underscores need to use trends
• Underscores need to use same assays/timing of
  samples

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Variations in Measurement

• Significant variation in measured serum P values
  depending on the EXACT machine used to measure P
  even using the same assay technique.
• Using phosphomolybdate UV assay the mean values
  range from 4.82 to 5.64 between 2 different
  machines
• These lab differences will create HUGE cost
  differences in care and potentially expose
  patients to more risk for over or under use of
  drugs.

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Diagnosis of CKD-MBD Biochemical Abnormalities

• In the initial CKD stagea, the recommendation is
  to monitor serum levels of
• Phosphorus
• Calcium
• PTH
• Alkaline phosphatase
• In CKD stages 3-5Db, frequency of monitoring
  serum calcium, phosphorus, and PTH should be
  based
• On the presence and magnitude of abnormalities
• The rate of progression of CKD
• In childrenc, the suggestion is to begin
  monitoring in CKD stage 2

a. 3.1.1 (1C) b. 3.1.2 (not graded) c. 3.1.1
(2D)
KDIGO. Kid Int. 2009 76 (Suppl 113)S1-S130
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Diagnosis of CKD-MBD Biochemical Abnormalities

• In CKD stages 3-5D, the suggestionsa are to
• Might Measure 25(OH)D (calcidiol) levels
• Repeat testing on the basis of
• Baseline values
• Therapeutic interventions
• In the absence of knowing the optimum levels and
  the issues related to measurement, the decision
  on whether, when, how often to measure must be
  individualized. Consider how the measure will
  impact management and treatment decisions and the
  level of resources available
• Correct vitamin D deficiency and insufficiency in
  accordance to treatment strategies recommended
  for the general population.

KDIGO. Kid Int. 2009 76 (Suppl 113)S1-S130
a. 3.1.3 (2C)
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Serum Vitamin D Measurement May Not Reflect What
You Give to Your Patients
Cavalier E et al JBMR 2008
Not from KDIGO
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Not all Vitamin D Assays are Equal

• We thus believe that in countries where
  vitamin D2 is prescribed (even in a low
  proportion of patients, as in France), 25-OH-D
  assays should measure both 25-OH-D2 and 25-OH-D3
  and that the only interesting information to be
  provided to physicians in clinical practice is
  the sum of the 25-OH-D2 and 25-OH-D3
  concentrations.
• Massart and Souberbielle, Clin Chemistr 55 (6)
  1247 (2009)

Not from KDIGO
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Not all Vitamin D Assays are Equal

• Method
• competitive two-step chemiluminescence assay
• Sample material
• serum, EDTA plasma, lithium heparin plasma
• Measuring range
• 4.0 - 150 ng/mL
• Specificity
• 25-OH Vitamin D2 104
• 25-OH Vitamin D3 100

Not from KDIGO
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Diagnosis of CKD-MBD Biochemical Abnormalities

• In patients with CKD stages 3-5D,
• The recommendationa is that therapeutic decisions
  should be based on
• Trends versus a single laboratory value
• All available CKDMBD assessments
• The suggestionb is that medical practice should
  be guided by
• The evaluation of individual values of serum
  calcium and phosphorus together
• Rather than the calciumphosphorus product (Ca x
  P)

KDIGO. Kid Int. 2009 76 (Suppl 113)S1-S130
a. 3.1.4 (1C) b. 3.1.5 (2D)
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Evaluation of CKD-MBD Biochemical Abnormalities
Phosphorus Calcium
CKD Stage/GFR Range (mL/min/1.73 m2) KDIGO
3/3059 Every 6 12 months
4/1529 Every 3 6 months
5/lt15 or dialysis Every 1 3 months
PTH
CKD Stage/GFR Range (mL/min/1.73 m2) KDIGO
3/3059 Based on baseline level and CKD stage
4/1529 Every 6 12 months
5/lt15 or dialysis Every 3 6 months
KDIGO. Kid Int. 2009 76 (Suppl 113)S1-S130
a. 3.1.4 (1C) b. 3.1.5 (2D)
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Targets

• Evidence based
• Highest design level research -often unavailable
• Observational data
• KDOQI based primarily on observational
• KDIGO based on high level evidence most
  topics have little or none
• Common sense recommendations

Not from KDIGO
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PTH

• PTH synthesis/secretion occurs in response to low
  calcium, high phos, and low 1,25 vitamin D
  levels.
• Synthesis/secretion are suppressed by high
  calcium, high calcitriol, and high FGF 23 levels.
• PTH is oscillatory but blunted in CKD
• Ionized Calcium is the most critical determinent
  of minute to minute PTH secretion.

Not from KDIGO
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PTH

• Secretion happens within minutes
• Synthesis happens within hours/days
• Diffuse hyperplasia ? early nodularity ? ? single
  nodule happens over weeks to years

Not from KDIGO
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SHPT

• Progressive disease
• Increased secretion and synthesis
• Hyperplasia
• Chronic elevation of PTH
• Abnormal calcium, phos and vit D metabolism
  contribute to development and severity
• Associated with adverse clinical outcomes
  including bone and soft tissue abnormalities

Not from KDIGO
31
What is the target?

• Problems with sample collection and variability
  raise significant concerns re setting an absolute
  level and their strict use as a clinically
  relevant biomarker
• However, to not measure or treat is equally
  concerning.
• Use of trends is critical absolute or optimal
  target is questionable
• But..

32
Bio vs Intact

• Benefit of bio has not been demonstrated
• 1-84 creates bone resorption, 7-84 is
  antagonistic to bone resorption

33
Random action chaos

• Protocols allow us to see the outcomes of our
  interventions
• They allow immediate intervention on MD behalf
  based on reasonable judgment and

Not from KDIGO
34
1994

• Lab available, reviewed by clinical staff
• MD called regarding out of range levels and
  intervention requested
• No action for the patient until MD response

35
1995

• Lab available, clinical staff review
• Per protocol, binders, vitamin D, calcimimetics
  adjusted per protocol
• Consistent intervention for pt-specific labs
• MD notification
• Collaboration on pts who dont fit protocol
  (10-20 of patients)

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KDIGO Diagnosis of CKD-MBDVascular
Calcification
37
Calcification

• In non-CKD, magnitude of Coronary Artery
  Calcification (CAC) by (EBCT) or multi-slice
  computed tomography (MSCT) is a strong predictor
  of CV event risk.
• In the CKD, coronary artery/generalized vascular
  calcification is exceedingly more prevalent,
  severe, and accelerated.
• Ref standard for detecting CV calcification is
  CT-based CAC score, but other techniques (lateral
  abdominal X-ray, pulse wave velocity (PWV),
  echocardiography may yield good information.
• Presence/severity of CV calcification strongly
  predict CV morbidity and mortality CKD.

38
Calcification

• There is limited CKD, RCT evidence that slowing
  arterial calcification impacts mortality.
• A small majority of WG members felt that
  inconsistencies remained in RCT reports aimed to
  demonstrate that intervention improved pt level
  outcomes, thus indiscriminate screening not rec
  for every CKD-MBD.
• Implies that screening is done at discretion of
  treating MD, especially if knowledge of
  calcification may impact therapeutic decision
  making Consensus that known vascular/valvular
  calcification and its magnitude identify patients
  at high CV risk. Therefore, the presence of
  vascular/valvular calcification should be
  considered for individualized tx of CKD-MBD.

39
Arterial Media Calcification in ESRD Impact on
All-Cause and Cardiovascular Mortality

• Arterial Medial Calcification
• usually observed in
• young and middle-aged patients without
  conventional atherosclerotic risk factors
• associated with
• duration of HD
• calcium-phosphate disorders
• oral dose of elemental calcium prescribed as a
  phosphate binder (CaCO3)

• Arterial Intimal
• Calcification
• usually observed in
• older patients with a clinical history of
  atherosclerosis before starting HD
• those with typical risk factors associated with
  atherosclerotic disease

n202 ESRDend-stage renal disease HDhemodialysi
s
Not from KDIGO
For illustration purposes only
London GM, Guerin AP, Marchais SJ, Metivier F,
Pannier B, Adda H. Nephrol Dial Transplant.
2003181731-1740.
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Diagnosis of CKD-MBD Vascular Calcification

• In CKD stages 3-5D, the suggestionsa indicate
  that
• It is reasonable to use alternatives to computed
  tomography-based imaging to detect the presence
  or absence of vascular calcification, including
• Lateral abdominal radiograph
• Echocardiogram
• Patients with known vascular/valvular
  calcification can be considered at highest
  cardiovascular risk
• It is reasonable to use this information to guide
  the management of CKDMBD

a. 3.3.1 (2C)
KDIGO. Kid Int. 2009 76 (Suppl 113)S1-S130
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Diabetes and CKD Compounded Risk for Vascular
Calcification

• Diabetes has been identified as an independent
  risk factor for vascular calcification
• Coexistence of diabetes and CKD potentiate
  vascular calcification dramatically versus either
  condition alone
• In fact, more than 65 percent of people with
  diabetes die from cardiovascular disease or
  stroke

Multistage probability sample from 2000-2002, pts
between 30-65yrs, logistic regression was used to
examine the association between stages of CKD
and CAC scores (gt 10, gt100, gt400 vs 10 or less in
nonCKD. CKD was defined as GFR gt 60 for stage 1,
2 and lt 60 for stages 3-5 (excluding dialysis).
Kramer H, Toto R, Peshock R, Cooper, R, Victor R
Association between chronic kidney disease and
coronary artery calcification the Dallas Heart
Study American Diabetes Association. Diabetes
heart disease and stroke. www.diabetes.org.
http//www.diabetes.org/diabetes-heart-disease-str
oke.jsp. Accessed April 8, 2009.
Not from KDIGO
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Treatment of CKD-MBD Phosphorus and Calcium
43
Defining Normal
Normal Phosphorus 2.5 mg/dl 4.5 mg/dl
Normal Calcium 8.5 mg/dl 10mg/dl or 10.5 mg/dl
Normal iPTH (varies with the assay used) 10 pg/ml - 65 pg/ml Centers for Disease Control recommendations

• Normal for healthy individuals.

44
Hyperphosphatemia
Despite a lack of RCT evidence, it is reasonable
to lower P in CKD patients using phosphate
binders. Additional options to lower phosphorus
include limiting dietary phosphate intake (while
ensuring adequate protein intake) and/or
increasing frequency or duration of dialysis (in
those who require renal replacement therapy).
Insufficient evidence that any specific
phosphate binder significantly impacts
patient-level outcomes. Thus, the choice of
phosphate binder should be individualized, and
the guidance offered in this recommendation is
based on effects of the available agents on a
range of clinical parameters, rather than on
phosphorus-lowering alone.
45
Hyperphosphatemia

• Associated w/poor outcomes/mortality in CKD Stage
  5D high normal P levels associated with
  mortality in non-CKD patients/Stage 3 patients.
• CKD Stages 4-5D commonly have a high P linked to
  the development of CKD-MBD, including SHPT,
  reduced calcitriol levels, abnormal bone
  remodeling, soft-tissue calcification.
• May directly cause or exacerbate other aspects of
  CKD-MBD, specifically secondary HPT, a reduction
  in calcitriol levels, bone disease, and arterial
  calcification.
• No evidence that lowering serum P to a specific
  target range leads to improved clinical outcomes
  in patients with CKD.
• Recommended goals of therapy must therefore be
  based on observational data.

46
Treatment w/ Phosphate Binders is Independently
Associated w/ Improved Survival Among CKD 5D

• Prospective cohort study of 10,044 incident
  hemodialysis patients comparing 1-year all-cause
  mortality among patients who were or were not
  treated with phosphate binders
• The phosphate bindertreated group had a
  significantly lower mortality rate than the
  untreated group (Plt0.0001)
• The 1,434 patients who began treatment with
  phosphorus binders before dialysis demonstrated a
  significant survival advantage compared with
  5,055 patients who were treated in the first 90
  days (P0.0008)

Isakova T, Gutiérrez OM, Chang Y, et al.
Phosphorus binders and survival on hemodialysis.
J Am Soc Nephrol. 200920388-396.
Not from KDIGO
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Treatment Target Ranges
Stage Target PO4 Target Ca
3 KDIGO Maintain Normal KDOQI 2.7-4.6 mg/dL KDIGO Maintain Normal KDOQI Normal for Lab
4-5 KDIGO Maintain Normal KDOQI 2.7-4.6 mg/dL KDIGO Maintain Normal KDOQI Normal for Lab
5D KDIGO Towards Normal KDOQI 3.5-5.5 mg/dL KDIGO Maintain Normal KDOQI 8.4-9.5 mg/dL
KDIGO. Kid Int. 2009 76 (Suppl 113)S1-S130
K/DOQI clinical practice guidelines for bone
metabolism and disease in chronic kidney disease.
Am J Kidney Dis. 2003(suppl 3)
48
Treatment of CKD-MBDPhosphorus and Calcium

• In patients with CKD stages 3-5, the suggestions
  are to
• Maintain serum phosphorus in the normal rangea
• Maintain serum calcium in the normal rangeb
• Phosphate binders are suggested in the treatment
  of hyperphosphatemiac
• For choice of phosphate binder, it is reasonable
  to take into accountc
• CKD stage
• Presence of other components of CKD-MBD
• Concomitant therapies
• Side-effect profile

a. 4.1.1 (2C) b. 4.1.2 (2D) c. 4.1.4 (not
graded)
KDIGO. Kid Int. 2009 76 (Suppl 113)S1-S130
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Treatment of CKD-MBDPhosphorus and Calcium

• In patients with CKD stages 5D, the suggestion is
  to
• Lower elevated phosphorus levels toward normal
  rangea
• Use a dialysate calcium concentration between
  1.25 and 1.5 mmol/l (2.5 and 3.0 meq/L)b

a. 4.1.3 (2C) b. 4.1.2 (2D)
KDIGO. Kid Int. 2009 76 (Suppl 113)S1-S130
50
Treatment of CKD-MBDPhosphorus and Calcium

• In patients with CKD stages 3-5D and
  hyperphosphatemia, the recommendationa is to
• Restrict calcium based phosphate binders in the
  presence of
• Arterial calcification
• Adynamic bone disease
• Persistently low serum PTH levels
• Restrict the dose of calcium based phosphate
  binders and/or restrict the dose of calcitriol or
  vitamin D analog are suggestedb, in the presence
  of
• Persistent or recurrent hypercalcemia

a. 4.1.5 (1B) b. 4.1.5 (2C)
KDIGO. Kid Int. 2009 76 (Suppl 113)S1-S130
51
Patients In Whom it may be prudent to Modify
Calcium Load
Calcification
Persistently Low PTH
ABD
Hypercalcemia
1,2,3
2
2,3,4
51 - 83
57
16 - 54
5 40 CKD 3/46 20 50 HD6 40 70 PD5
Recommended for Calcium Restriction
1Russo D, Corrao S, Miranda I, et al. Am J Neph
200727152-158 2Chertow GM, Burke SK, Raggi P,
et al. Kidney Int. 200262245-252 3Block GA,
Spiegel DM, Ehrlich J, et al. Kidney Int.
2005681815-1824 4Qunibi W, Moustafa M, Muenz
LR, et al. AJKD. 2008 5Andress D.Kid Int.
2008731345-1354 6KDIGO. Kid Int. 2009 76
(Suppl 113)S1-S130
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Phosphate Binding Compounds
KDIGO. Kid Int. 2009 76 (Suppl 113)S1-S130
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How can we do it?
54
(No Transcript)
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Area of focus Phosphorus Control

• Various binders
• Consider Advantages/Disadvantages for individual
  pt
• Individual tolerance
• GI side effects seem to be dose related
• Try again with lower dose
• Use combination

56
PTH Levels
57
Treatment Initiation Ranges
Stage Treatment Initiation Range iPTH
3 KDIGO gt Upper limit of Normal 4.2.2 (2C) KDOQI 35-70 pg/mL
4 KDIGO gt Upper limit of Normal 4.2.2 (2C) KDOQI 70-110 pg/mL
5 KDIGO gt Upper limit of Normal 4.2.2 (2C) KDOQI 150-300 pg/mL
5D KDIGO 2 to 9x upper limit of Normal 4.2.3 (2C) KDOQI 150-300 pg/mL
58
Treatment of Abnormal PTH levels in CKD-MBD

• In patients with CKD stages 3-5 not on dialysis,
  the optimal PTH level is unknown
• In patients with levels of intact PTH (iPTH)
  above the upper normal limit of the assay, the
  suggestiona is to, first evaluate for
• Hyperphosphatemia
• Hypocalcemia
• Vitamin D deficiency
• It is reasonable to correct these abnormalities
  with any or all of the followingb
• Reducing dietary phosphate intake and
  administering phosphate binders, calcium
  supplements, and/or native vitamin D
• The suggestionc is to treat with calcitriol or
  vitamin D analogs if
• Serum PTH is progressively rising and remains
  persistently above the upper limit of normal for
  the assay despite correction of modifiable
  factors

KDIGO. Kid Int. 2009 76 (Suppl 113)S1-S130
a. 4.2.1 (2C) b. 4.2.1 (not graded) c. 4.2.2
(2C)
59
Treatment of Abnormal PTH levels in CKD-MBD

• In patients with CKD stage 5D, the suggestiona is
  to
• Maintain iPTH levels in the range of
  approximately two to nine times the upper normal
  limit for the assay
• To lower PTH, when it is elevated or rising, the
  suggestiona is to use
• Calcitriol
• Or vitamin D analogs
• Or calcimimetics
• Or a combination of calcimimetics and calcitriol
  or vitamin D analogs
• In patients with severe hyperparathyroidism who
  fail to respond to medical/pharmacological
  therapy parathyreidectomy is suggested

KDIGO. Kid Int. 2009 76 (Suppl 113)S1-S130
a. 4.2.3 (2C) b. 4.2.5 (2B)
60
Treatment of Abnormal PTH Levels In CKD-MBD

• In patients with hypocalcemia, the suggestiona is
  to reduce or stop
• calcimimetics depending on severity, concomitant
  medications, and clinical signs and symptoms
• If intact PTH levels fall below two times the
  upper limit of normal for the assay, the
  suggestionb is to reduce or stop
• Calcitriol
• Vitamin D analogs
• And/or calcimimetics

a. 4.2.4 (2B) b. 4.2.4 (2C)
KDIGO. Kid Int. 2009 76 (Suppl 113)S1-S130
61
In Summary
KDIGO International Clinical Practice Guidelines
PTH
Calcium
Phosphorus

• Calcification represents highest risk
• Detect with x-ray or ultrasound
• Limit Calcium in
• Hypercalcemia
• Calcification
• Low PTH
• ADBD

Evaluate PTH in context of alkaline phosphatase,
serum P, serum Ca, vitamin D deficiency/ replaceme
nt avoid extreme 2-9x upper norm Marked changes
should trigger treatment changes Decrease
cinacalcet in event of hypocalcemia
Goal Normal or toward normal
Treat the trends Treat P and Ca to normal, PTH
Avoid Extremes
KDIGO. Kid Int. 2009 76 (Suppl 113)S1-S130