Transcript kdigo

LINEE GUIDA, KDIGO
E DIALISI PERITONEALE
GIANCARLO MARINANGELI
U.O.C. NEFROLOGIA E DIALISI
GIULIANOVA
KDOQI and KDIGO
NKF- Kidney Disease Outcome Quality Initiative
2003
Targets for treatment
Kidney Disease Improving Global Outcomes
2009
Range of risks
From Renal Osteodystrophy to
Chronic Kidney Disease - Mineral Bone Disorder
(CKD – MBD)
Kidney Int 2006; 69: 1945-53
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 Ca, P, PTH,
or vit. D metabolism
– Abnormalities in bone
turnover, mineralization,
volume, linear growth, or
strength
– Vascular or other soft tissue
calcification
Moe et al. Kidney Int 2006;69:1945-1953
K-DIGO: THE CHALLENGES
The definition CKD-MBD was new and not used in published
clinical studies. Thus each of the three components had
to be addressed separately
The complexity of pathogenesis make it difficult to
differentiate a consequence of the disease from a
consequence of its treatment
Differences throughout the world in nutrient intake,
availability of medications and clinical practice.
KDIGO: Clinical Practice Guideline for the
Diagnosis, Evaluation, Prevention, and
Treatment of CKD-MBD
Key Categories in KDIGO
Diagnosis/Evaluation
Vascular Calcification
Treatment
KDIGO: Grading of Recommendations
Strength of
Recommendation
Implications
“We recommend …”
Level 1
“Most patients should receive the
recommended course of action.”
“We suggest …”
Level 2
“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
KDIGO: Diagnosis of CKD-MBD
Biochemical Abnormalities
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. Kidney Int. 2009; 76 (Suppl 113):S1-S130
Diagnosis of CKD-MBD:
Biochemical Abnormalities
 In patients with CKD stages 3-5D, the suggestionsa are
to:
– Measure 25(OH)D (calcidiol) levels
– Repeat testing on the basis of:
 Baseline values
 Therapeutic interventions
– Correct vitamin D deficiency and insufficiency in
accordance to treatment strategies recommended for
the general population
a. 3.1.3 (2C)
KDIGO. Kidney Int. 2009; 76 (Suppl 113):S1-S130
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 CKD–MBD 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 Ca x P product
a. 3.1.4 (1C); b. 3.1.5 (2D)
KDIGO. Kidney Int. 2009; 76 (Suppl 113):S1-S130
Evaluation of CKD-MBD:
Biochemical Abnormalities
Phosphate and Calcium
CKD Stage
KDIGO
3
Every 6–12 months
4
Every 3–6 months
5 or D
Every 1–3 months
Evaluation of CKD-MBD:
Biochemical Abnormalities
PTH
CKD Stage
KDIGO
3
Based on baseline level and
CKD stage
4
Every 6–12 months
5 or D
Every 3–6 months
Treatment of CKD-MBD:
Phosphorus and Calcium
Definition of “Normal” values
Phosphorus
2.5– 4.5 mg/dl
Calcium
8.5 – 10 (or 10.5) mg/dl
iPTH
10 - 65 pg/ml
(varies with the assay used)
[Centers for Disease Control
“Normal” means within the above ranges. These are normal
ranges for healthy individuals.
recommendations]
Treatment of CKD-MBD:
Phosphorus and Calcium
 In patients with CKD stages 3-5, the suggestions are to:
– Maintain serum P in the normal range a
– Maintain serum Ca in the normal range b
 Phosphate binders are suggested in the treatment of
hyperphosphatemia c
 For choice of phosphate binder, it is reasonable to take
into account c:
– 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. Kidney Int. 2009; 76 (Suppl 113):S1-S130
Treatment of CKD-MBD:
Phosphorus and Calcium
 In patients with CKD stages 5D, the suggestion is to:
– Lower elevated P levels toward normal range (2C)
– Use a dialysate Ca concentration between 1.25 and
1.5 mmol/l (2.5 and 3.0 meq/L) (2D)
– Increase dialytic phosphate removal in the treatment
of persistent hyperphosphatemia (2C)
a. 4.1.3 (2C); b. 4.1.2 (2D); c
4.1.8 (2C)
KDIGO. Kidney Int. 2009; 76 (Suppl 113):S1-S130
Treatment of CKD-MBD:
Phosphorus 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. Kidney Int. 2009; 76 (Suppl 113):S1-S130
Patients In Whom it is Recommended
Calcium Be Restricted
Calcification
1,2,3
51% - 83%
Persistently
Low PTH
2
57%
Hypercalcemia
ABD
2,3,4
16% - 54%
5 – 40% CKD 3,4,6
20 – 50 % HD 6
40 – 70% PD 5
Calcium
Restriction
1 Russo
D, et al. Am J Neph 2007;27:152-158
2 Chertow GM, et al. Kidney Int. 2002;62:245-252
3 Block GA, et al. Kidney Int. 2005;68:1815-1824
4 Qunibi W, et al. AJKD. 2008
5 Andress D. Kidney Int. 2008;73:1345-1354
6 KDIGO. KI 2009; 76 (Suppl 113):S1-S130
Phosphate Binding Compounds
KDIGO. Kid Int. 2009; 76 (Suppl 113):S1-S130
KDOQI / KDIGO - treatment
recommendations in 5D:
Laboratory values
KDOQI
Recommend.
Grading
KDIGO
Recommend.
Grading
iPTH (pg/mL)
150 to 300
range 2 to 9 x
Evidence Suggested
ULN
2C
Corrected Ca
(mg/dL)
8.4 to 9.5
Suggested to maintain in
the normal range
2D
P (mg/dL)
3.5 to 5.5
Evidence Suggested to lower toward
the normal range
2C
CaxP (mg2/dL2)
<55
Evidence Not suggested
to direct clinical practice
N/A
Opinion
KDIGO Clinical Practice Guideline for CKD-MBD. Kidney Int 2009;76 (Suppl 113)
PTH Levels
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
a. 4.2.1 (2C); b. 4.2.1 (not graded); c. 4.2.2 (2C)
KDIGO. KI 2009; 76 (Suppl 113):S1-S130
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 (2C)
 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 (2B)
a. 4.2.3 (2C); b. 4.2.5 (2B)
KDIGO. Kidney Int. 2009; 76 (Suppl 113):S1-S130
Treatment of Abnormal
PTH Levels In CKD-MBD
 In patients with hypocalcemia, the suggestion
a
is to
reduce or stop:
– calcimimetics depending on severity, concomitant medications,
and clinical signs and symptoms (2B)
 If intact PTH levels fall below two times the upper limit
of normal for the assay, the suggestion b is to reduce or
stop:
 Calcitriol
 Vitamin D analogs
 And/or calcimimetics
a. 4.2.4 (2B); b. 4.2.4 (2C)
KDIGO. Kidney Int. 2009; 76 (Suppl 113):S1-S130
KDOQI / KDIGO - PTH TARGETS
CKD Stage
Target iPTH
(pg/ml) KDOQI
Grading
Target iPTH
(pg/ml) KDIGO
3
35 - 70
Opinion
Not known
4
70 - 110
Opinion
Not known
5 ND
150 - 300
Evidence
Not known
5D
150 - 300
Evidence
2 to 9 x ULN
Grading
2C
2C
2C
2C
KDIGO Clinical Practice Guideline for CKD-MBD. Kidney Int 2009;76 (Suppl 113)
KDIGO: Diagnosis of CKD-MBD
Vascular Calcification
Diagnosis of CKD-MBD:
Vascular Calcification
 In CKD stages 3-5D, the suggestionsa indicate that:
– It is reasonable to use alternatives to CT-based imaging to
detect vascular calcifications, including:
 Lateral abdominal radiograph
 Echocardiogram
– Patients with known vascular/valvular calcifications can be
considered at highest cardiovascular risk
– It is reasonable to use this information to guide the management
of CKD–MBD
a. 3.3.1 (2C)
KDIGO. Kidney Int. 2009; 76 (Suppl 113):S1-S130
Diagnosis of CKD-MBD:
Vascular Calcification
 In CKD stages 3-5D, the suggestionsa indicate that:
– It is reasonable to use alternatives to computed tomographybased 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 CKD–MBD
a. 3.3.1 (2C)
KDIGO. Kid Int. 2009; 76 (Suppl 113):S1-S130
Treatment of CKD-MBD:
What about PD?
4.1.3
…it is probably wise to mantain flexibility with dialysate Ca
concentrations…individualized whenever possible…to
meet specific patient requirements.
Similar considerations apply to PD, in which…Ca
concentrations…tailored to individual patient’s need.
Compared to HD…PD pts are exposed to a given dialysate
calcium concentration for longer periods of time.
Therefore…bags with Ca as high as 3.5 mEq/l (1.75 mmol/l)
are generally avoided to prevent calcium overload and the
induction of ABD.
Treatment of CKD-MBD:
What about PD?
4.1.3
Concentrations between 1.25 and 1.50 mmol/l (2.5
and 3.0) mEq/l are recommended.
PD related points:
- more calcium as phosphate binder?
- residual renal function
- continous, not intermittent, treatment
- new solutions, variable Ca
Treatment of CKD-MBD:
What about PD?
 In most cases Calcium balance is slightly
positive in CAPD with four exchanges and 1,75
mEq/l Ca…
…and slightly negative with Ca 1,25 mEq/l
S. Bertoli – 2009
O. Simonsen- KI 2003
RIMOZIONE DEL FOSFORO IN
DIALISI PERITONEALE
- FUNZIONE RENALE RESIDUA
- PERMEABILITA’ PERITONEALE
- SCHEMA DIALITICO
RIMOZIONE DEL FOSFORO IN DP
FUNZIONE RENALE RESIDUA
24 pazienti incidenti in DP – GFR start 59,9 L/sett – 7,1 mesi di follow up
Bammens et al, AJKD 2000
CLEARANCE CREATININA
100
CLEARANCE UREA
CLEARANCE FOSFORO
Litri / settimana / 1,73 mq di BSA
80
60
40
20
1
2
3
4
5
VISITE
RIMOZIONE DEL FOSFORO IN DP
FUNZIONE RENALE RESIDUA
r =0,49
y = 0,6421x
R2 = 0,6848
Analisi cross-sectional su 33 pazienti in DP
una misura - un paziente, 17 in CAPD, 24 M
CLEARANCE CREATININA = 5,15 ± 2,91 ml/min
CLEARANCE UREA = 2,70 ± 1,46 ml/min
CLEARANCE FOSFORO = 2,50 ± 1,73 ml/min
r =0,94
Neri et al – SIN 2007
RIMOZIONE DEL FOSFORO IN DP
PERMEABILITA’ PERITONEALE
Lilaj et al, AJKD 1999
15 pazienti, PET standard
1
0,9
D/P
0,8
Gallar et al, Nefrologia 2000
70 pazienti, PET standard
fosforo
0,9
creatinina
0,8
D/P creat 4 h
0,7
0,6
0,5
0,4
0,3
0,7
0,6
0,5
0,2
0,1
ore
0
0
2
4
0,4
0,2
0,4
0,6
0,8
D/P fosforo 4 h
RIMOZIONE DEL FOSFORO IN DP
PERMEABILITA’ PERITONEALE
Relazione tra il D/P4h del fosforo e D/P4h di creatinina ed urea.
Primo PET (a 4.4±3.0 mesi dall’inizio della DP), 57 pazienti.
Neri et al, SIN 2007
y = 0,997 x - 0,03
R2 = 0,7441
D/P fosforo 4 h
1,0
0,8
0,8
0,6
0,6
0,4
0,4
0,2
0,2
0,2
0,4
0,6
y = 1,136x - 0,41
R2 = 0,282
1,0
0,8
1,0
D/P creatinina 4 h
0,2
0,4
0,6
0,8
1,0
D/P urea 4 h
RIMOZIONE DEL FOSFORO IN DP
Il trasporto peritoneale del fosforo è:
- simile a quello della creatinina (e < a quello dell’urea)
- risente molto della permeabilità peritoneale
- tanto minore quanto maggiore è l’intermittenza del trattamento
L’eliminazione renale è:
- simile a quella dell’urea
- inferiore a quella della creatinina
In Summary …
KDIGO International Clinical Practice Guidelines
Phosphorus
Calcium
PTH
Calcification represents the
highest risk
Evaluate PTH in context
of hyperP, hypoCa,
vitamin D deficiency
Detect with x-ray/ultrasound
Goal = Normal
Restrict Calcium in
1.
Hypercalcemia
2.
Calcification
3.
Low PTH
4.
ADBD
Marked changes should
trigger treatment changes
Decrease cinacalcet in
event of hypocalcemia
Treat the trends: Treat P and Ca to normal, PTH to Goal
KDIGO. Kidney Int. 2009; 76 (Suppl 113):S1-S130
GRAZIE PER L’ATTENZIONE
K-DIGO (global non-profit foundation)
Mission Statement
To improve the care and outcomes of
kidney disease patients worldwide
through promoting coordination,
collaboration and integration of
initiatives to develop and implement
clinical practice guidelines.