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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.
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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 2009Range 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, andTreatment of CKD-MBD
Key Categories in KDIGO Diagnosis/Evaluation Vascular Calcification Treatment
KDIGO: Grading of Recommendations 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
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
Definition of “Normal” values “Normal” means within the above ranges. These are normal ranges for healthy individuals.
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 Persistently Low PTH Hypercalcemia ABD 1,2,3 2,3,4 2 51% - 83% 57% 16% - 54% 5 – 40% CKD 3,4,6 20 –50 % HD 6 40 – 70% PD 5 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 Calcium Restriction
Phosphate Binding Compounds KDIGO. Kid Int. 2009; 76 (Suppl 113):S1-S130
KDOQI / KDIGO -treatment recommendations in 5D: • KDIGO Clinical Practice Guideline for CKD-MBD. Kidney Int 2009;76 (Suppl 113)
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)
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 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 CLEARANCE UREA CLEARANCE FOSFORO 100 Litri / settimana / 1,73 mq di BSA 80 60 40 20 2 3 4 5 1 VISITE
RIMOZIONE DEL FOSFORO IN DP FUNZIONE RENALE RESIDUA 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 =0,49 y = 0,6421x R2 = 0,6848 r =0,94 Neri et al – SIN 2007
RIMOZIONE DEL FOSFORO IN DP PERMEABILITA’ PERITONEALE Lilaj et al, AJKD 1999 15 pazienti, PET standard Gallar et al, Nefrologia 2000 70 pazienti, PET standard D/P 0,9 0,8 0,7 D/P creat 4 h 0,6 0,5 0,4 ore 0,6 0,8 0,2 0,4 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 D/P fosforo 4 h D/P creatinina 4 h 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 Evaluate PTH in context of hyperP, hypoCa, vitamin D deficiency Marked changes should trigger treatment changes Decrease cinacalcet in event of hypocalcemia Goal = Normal • Calcification represents the highest risk • Detect with x-ray/ultrasound • Restrict Calcium in • Hypercalcemia • Calcification • Low PTH • ADBD Treat the trends: Treat P and Ca to normal, PTH to Goal KDIGO. Kidney Int. 2009; 76 (Suppl 113):S1-S130
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.