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LINEE GUIDA, KDIGO E DIALISI PERITONEALE
GIANCARLO MARINANGELIU.O.C. NEFROLOGIA E DIALISI
GIULIANOVA
KDOQI and KDIGO
2003 Targets for treatment
2009 Range of risks
NKF- Kidney Disease Outcome Quality Initiative
Kidney Disease Improving Global Outcomes
Kidney Int 2006; 69: 1945-53
From Renal Osteodystrophy to Chronic Kidney Disease - Mineral Bone Disorder
(CKD – MBD)
Moe et al. Kidney Int 2006;69:1945-1953
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
Chronic Kidney Disease – Mineral Bone Disorder(CKD – MBD)
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
Treatment
Vascular Calcification
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
KDIGO. Kid Int. 2009; 76 (Suppl 113):S1-S130
“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: Diagnosis of CKD-MBDBiochemical 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
KDIGO. Kidney Int. 2009; 76 (Suppl 113):S1-S130a. 3.1.3 (2C)
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
CKD Stage KDIGO
3 Every 6–12 months
4 Every 3–6 months
5 or D Every 1–3 months
Phosphate and Calcium
Evaluation of CKD-MBD: Biochemical Abnormalities
CKD Stage KDIGO
3 Based on baseline level and CKD stage
4 Every 6–12 months
5 or D Every 3–6 months
PTH
Treatment of CKD-MBD: Phosphorus and Calcium
Definition of “Normal” values
“Normal” means within the above ranges. These are normal ranges for healthy individuals.
Phosphorus 2.5– 4.5 mg/dl
Calcium 8.5 – 10 (or 10.5) mg/dl
iPTH(varies with the assay used)
10 - 65 pg/ml[Centers for Disease Control
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 hypercalcemiaa. 4.1.5 (1B); b. 4.1.5 (2C) KDIGO. Kidney Int. 2009; 76 (Suppl 113):S1-S130
51% - 83% 57% 16% - 54%
CalcificationPersistently
Low PTHABDHypercalcemia
1,2,32
2,3,4
Patients In Whom it is Recommended Calcium Be Restricted
1 Russo D, et al. Am J Neph 2007;27:152-1582 Chertow GM, et al. Kidney Int. 2002;62:245-2523 Block GA, et al. Kidney Int. 2005;68:1815-18244 Qunibi W, et al. AJKD. 20085 Andress D. Kidney Int. 2008;73:1345-13546 KDIGO. KI 2009; 76 (Suppl 113):S1-S130
Calcium Restriction
5 – 40% CKD 3,4,6
20 – 50 % HD 6
40 – 70% PD 5
Phosphate Binding Compounds
KDIGO. Kid Int. 2009; 76 (Suppl 113):S1-S130
KDOQI / KDIGO - treatment recommendations in 5D:
Laboratory valuesKDOQI
Recommend.Grading
KDIGO
Recommend.Grading
iPTH (pg/mL) 150 to 300 Evidence Suggested range 2 to 9 x ULN 2C
Corrected Ca (mg/dL) 8.4 to 9.5 Opinion 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
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
KDIGO Clinical Practice Guideline for CKD-MBD. Kidney Int 2009;76 (Suppl 113)
CKD StageTarget iPTH
(pg/ml) KDOQIGrading
Target iPTH (pg/ml) KDIGO
Grading
3 35 - 70 Opinion Not known2C
4 70 - 110 Opinion Not known 2C
5 ND 150 - 300 Evidence Not known2C
5D 150 - 300 Evidence 2 to 9 x ULN 2C
KDIGO: Diagnosis of CKD-MBDVascular 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 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 CKD–MBD
KDIGO. Kid Int. 2009; 76 (Suppl 113):S1-S130a. 3.3.1 (2C)
4.1.3
…it is probably wise to mantain flexibility with dialysate Ca concentrations…individualized whenever possible…to meet specific patient requirements.
Treatment of CKD-MBD:What about PD?
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.
4.1.3
Concentrations between 1.25 and 1.50 mmol/l (2.5 and 3.0) mEq/l are recommended.
Treatment of CKD-MBD:What about PD?
PD related points:
- more calcium as phosphate binder?
- residual renal function
- continous, not intermittent, treatment
- new solutions, variable Ca
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
Treatment of CKD-MBD:What about PD?
S. Bertoli – 2009
O. Simonsen- KI 2003
RIMOZIONE DEL FOSFORO INDIALISI PERITONEALE
- FUNZIONE RENALE RESIDUA
- PERMEABILITA’ PERITONEALE
- SCHEMA DIALITICO
RIMOZIONE DEL FOSFORO IN DPFUNZIONE RENALE RESIDUA
24 pazienti incidenti in DP – GFR start 59,9 L/sett – 7,1 mesi di follow up
Bammens et al, AJKD 2000
100
80
60
40
20
Litri / settimana / 1,73 mq di BSA
CLEARANCE CREATININA CLEARANCE UREA CLEARANCE FOSFORO
1 2 3 4 5 VISITE
RIMOZIONE DEL FOSFORO IN DPFUNZIONE RENALE RESIDUA
r =0,94
Analisi cross-sectional su 33 pazienti in DPuna misura - un paziente, 17 in CAPD, 24 MCLEARANCE CREATININA = 5,15 ± 2,91 ml/min
CLEARANCE UREA = 2,70 ± 1,46 ml/min
CLEARANCE FOSFORO = 2,50 ± 1,73 ml/min
Neri et al – SIN 2007
r =0,49
y = 0,6421xR2 = 0,6848
RIMOZIONE DEL FOSFORO IN DPPERMEABILITA’ PERITONEALE
0
0,1
0,2
0,3
0,4
0,5
0,6
0,7
0,8
0,9
1
0 2 4
fosforo
creatinina
D/P
Lilaj et al, AJKD 199915 pazienti, PET standard
ore 0,4
0,5
0,6
0,7
0,8
0,9
0,2 0,4 0,6 0,8
D/P
cre
at 4
h
D/P fosforo 4 h
Gallar et al, Nefrologia 200070 pazienti, PET standard
y = 0,997 x - 0,03
R2 = 0,7441
0,2
0,4
0,6
0,8
1,0
0,2 0,4 0,6 0,8 1,0
y = 1,136x - 0,41
R2 = 0,282
0,2
0,4
0,6
0,8
1,0
0,2 0,4 0,6 0,8 1,0
D/P creatinina 4 h D/P urea 4 h
D/P
fo
sfo
ro 4
h
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
RIMOZIONE DEL FOSFORO IN DPPERMEABILITA’ PERITONEALE
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
RIMOZIONE DEL FOSFORO IN DP
In Summary …
Phosphorus
Goal = Normal
Calcium
Calcification represents the highest risk
Detect with x-ray/ultrasound
Restrict Calcium in1. Hypercalcemia2. Calcification3. Low PTH4. ADBD
PTH
Evaluate PTH in context of hyperP, hypoCa, vitamin D deficiency
Marked changes should trigger treatment changes
Decrease cinacalcet in event of hypocalcemia
KDIGO International Clinical Practice Guidelines
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.