chronic kidney disease - fmshk.com.hk · management of chronic kidney disease- fluids •kdigo 2013...
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Chronic kidney disease
Best practice management Dr Fiona Mackie
2016
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• Strategies to delay progression of disease
• Management of chronic kidney disease Anaemia Nutrition/fluids Growth failure Calcium/phosphate balance
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When the horse has bolted ………
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Anaemia • Prevalence data- children/adolescents with
CKD (Wong H KI 2006)
• Current definitions (KDIGO 2012)
CKD Stage Prevalence % Hb <12 mg/dl or treatment for anaemia
1-2 30%
3 66
4-5 93
Age Hb g/dl (g/L)
6 mo-5 yrs 11.0 (110)
5-12 yrs 11.5 (115)
12-15 yrs 12 (120)
Non pregnant females >15 yrs 12 (120)
Males >15 13 (130)
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Causes of anaemia
• Multifactorial: Erythropoetin deficiency, lack of iron availability, inflammation, blood loss, hyperparathyroidism, B12 and folate deficiency
www.kyoto-u.ac.jp
Usually lower O2 availability induces EPO production. As GFR, decreases there is a decrease in fractional Na reabsorption, therefore a decrease in oxygen use and therefore a decrease in EPO production
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Impact of anaemia in children
• Decreased Hb levels are independently associated with the development of LVH in children with CKD ( Mitsnefes JASN 2010)
• 52% increase in mortality risk in patients with hematocrit <33% at dialysis institution- NAPRTCS Warady et al Ped Neph 2003
• IPPN: increase in patient mortality of 5 vs 2% at 12 mths, 8 vs 4% at 24 mths with Hb <11g/dL (JASN 2013)
• Increased rate of hospitalisations
• Poorer school performance
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Treatment of anaemia- iron deficiency; absolute and functional
• How often should we measure?: KDIGO recommends measuring transferrin saturation (TSAT) and ferritin every 3 mths or more often if starting or adjusting ESA’s
• What should we measure?: KDIGO recommends Transferrin- indicator of total iron binding capacity but has diurnal variation and is nutritionally dependent
Serum ferritin- stored iron; but also an acute phase reactant • Most acceptable in children- TSAT ( serum iron/total
iron binding capacity x 100. Is derived from transferrin level x 1.4. Best predictor of iron deficiency TSAT <20%
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How should we treat iron deficiency?
• Iron target: KDIGO 2012 target saturation >20% and ferritin >100 ng/mL. Use oral iron first unless on HD- then use IV iron (trial data suggests more effective in children on HD)
• IV iron formulations- can have anaphylaxis (more common with iron dextran). Must be monitored appropriately with resuscitation facilities available. Problem if IV tissues (tattoo)
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Treating iron deficiency
• KDIGO 2012 recommendations for children (RCT evidence) If on HD: ferric gluconate 1.5 mg/kg weekly for 8 doses if iron deficient If on HD and iron replete 1 mg/kg/week and adjust according to iron studies
• If using oral iron- dose recommended for treatment in children is 2-6 mg/kg/day (elemental) in 2 divided doses
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Sometimes oral iron is not successful in PD or CKD patients
Sydney Children’s Hospital protocol for iron polymaltose Use pre-meds; monitor
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Iron polymaltose dosing for HD patients
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Erythropoietin analogues • KDIGO targets Hb 11-12
Available:
• Infants and young children may require much higher doses- much higher than adults. HD patients require more than PD patients (greater blood losses)
• Dose modification no more frequently than every 2 weeks
T 1/2 Dose Dosing frequency
Epoetin alfa 150 u/kg/wk 3 times per wk-weekly
Shorter half life
Darbopoetin IV 25 h; sc 48 h 0.45 µg/kg weekly or 0.75µg/kg q 2 weeks
1-2 weeks Painful on injection
Methoxy polyethylene glycol-epoietin beta (Mircera)
135 hrs 1.2 mcg/kg monthly
monthly Less painful; can be given monthly
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ESA resistance
• Either from the start or it develops over time • Possible causes
iron deficiency inflammation (increased hepcidin levels limits GI absorption in gut and liver release) bone disease ACEI/ARB acidosis vitamin C or folate deficiency malnutrition antibody to ESA- pure red cell aplasia- rare and hard to diagnose
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Fluids and nutrition
http://blog-health-nutrition.extension.umn.edu/2015/07/stay-hydrated-with-healthy-beverages-in.html
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Management of chronic kidney disease- Fluids
• KDIGO 2013 recommendations: Supplemental free water and sodium supplements should be given to children with CKD and polyuria to avoid chronic intravascular depletion and promote growth (Level 1C evidence)
• If hypertension >95 pc then sodium should be restricted to age based sodium requirement levels
Age Upper limit Na per day
<1 yr No data
1-3 yrs 1500 mg
4-8 1900
9-13 2200
14-18 2300
KDIGO 2013
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Protein energy wasting PEW (“malnutrition” in CKD)
Protein energy wasting
uremia
Orexigenic hormones
eg acyl grelin
Desacyl ghrelin,
adinopectin, letpin
GI losses eg vomiting from GOR; albumin
losses on PD or nephrotic
Altered taste Inadequate
caloric intake
anabolism
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Risk factors for PEW
• Infants
• Reduced residual renal function; inadequate dialysis dose
• Metabolic acidosis
• Low birth weight, small for gestational age
• Psychosocial factors
• Co-morbidity- neurological disease, CVS
• PD losses (of amino acids and proteins)
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Evaluation of nutrition in children with CKD
• Any unit looking after children with CKD should have access to a dietitian
• Why is it so important: For every 2 SDS above or below a BMI of 0.5 the risk of mortality increases by 26% in children ( u shape curve; Wong CS AM J KD 2000- ESKD children from USRDS data))
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What to evaluate and how?
• 3 day diet records from family
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Evaluation of nutrition
• nPCR is calculated from the intradialytic increase in BUN between HD sessions. A low nPCR predicts weight loss in adolescents on HD (evidence); recommended to measure monthly in adolescents on HD. Can use online calculators eg hsls.pitt.edu
• No good biochemical marker but albumin does correlate with mortality in children and adults so helps with severity
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Management of nutrition- few detailed guidelines
• CARI (Australia) 2005 Ensure the energy intake is that of a healthy child of the 50th percentile height of the same age to allow catch-up growth. If this can not be maintained orally, commence feeds nasogastric or gastrostomy
• Many studies have demonstrated improved growth especially in infants <2 yrs with MG/gastrostomy feeds in CKD (however not NAPRTCS study)
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Nutrition guidelines
• The net glucose intake from PD is 8% energy requirements per day- take this into account if overweight (Salusky 1983)
• Gastrostomy tubes should not be inserted at the time of a PD dialysis catheter (either well before or after) because of peritonitis risk
• KDOQI recommends measuring water soluble vitamins, zinc and copper every 4 months in dialysis patients and supplementing (not adult doses)
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Growth
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Short stature
• Definition: height of 2 SD’s below mean for age and sex (below the 2.5 percentile)
• Worse if infant onset of CKD • ESPN Data: 45% of children starting dialysis <
19yrs had a final adult height <3rd centile age/sex matched. However there have been improvements over the last 2 decades.
• Consequences: Increased mortality (complex includes influences of nutrition, bone disease etc); reduced QOL; poorer school performances and reduced income
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Risk factors for poor linear growth
• Infant onset of CKD
• Low birth weight and small for gestational age
• Protein energy wasting
• Incompatible dialysate solutions
• Inadequate dialysis dose (daily HD better growth than conventional)
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Growth hormone therapy
• GH stimulates linear growth, increases muscle mass and improves bone density
• Insensitivity to GH, reduced transcription of IGF1 • Effect of supraphysiological doses of GH- does
have a positive effect on final height. Better pre-dialysis; effect decreases after 1st year
• Metanalysis data: safe to use post transplant (no increased risk of rejection)
• Caution not to use in children with severe renal osteodystrophy- manage this first
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Simplified diagram showing muti-organ interactions in regulation of phosphate homoeostasis
FGF23 produced in the bone cells can suppress renal NaPi-2a and NaPi-2c co-transporter
activities to increase the urinary excretion of phosphate.
M. Shawkat Razzaque Clin. Sci. 2011;120:91-97 © 2011 by Portland Press Ltd
CKD Mineral Bone Disorder CKD-MBD
Suppression of renal alpha hydroxylase by FGF23/Klotho leads to reduced 1,25 OH2D
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FGF23 elevation
• Independent risk factor for mortality in adults with CKD and general population
• Why is it elevated in CKD? Not fully understood possibly oral phosphate loading transient increases in PTH reduced Klotho iron deficiency stimulates FGF 23 transcription in osteocytes
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Calcium based binders either have no effect or increase FGF 23
The appropriate therapy to minimise FGF23 rise and prevent CVS morbidity remains to be defined Salusky Ped Neph 2015
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Current CK-MBD recommendations • There are new guidelines to be released by KDIGO this year • Existing recommendations for phosphate are to maintain no higher
than age limits for CKD stages 1-4; lower targets for CKD stage 5 • Initially dietary restriction – even lower if raised PTH • 0 to 0.5 years – 100 mg/day • ●0.5 to 1 year – 275 mg/day • ●1 to 3 years – 460 mg/day • ●4 to 8 years – 500 mg/day • ●9 to 19 years – 1250 mg/day
• Phosphate binders- calcium containing vs non-calcium containing
(sevelemar)
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Calcium absorption from phosphate binders is increased if taken between meals and also if taking active vitamin D as well
Problem of hypercalcemia
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• 2 studies in children comparing sevelemar to calcium acetate. Equal reduction in phosphate, less hypercalcemia with sevelemar.
• Use both calcium and non-calcium containing binders to reduce cost.
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Management of CK-BMD
• PTH goals: if elevated reduce phosphate and then if still elevated start calcitriol
• PTH targets are controversial
• IPPN- for children on PD target PTH 1.7-3 times upper limit of normal
• Measure 25 hydroxyvitamin D and replace if low
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How often to measure?
• For calcium and phosphorus measurements, the KDOQI guidelines recommend [1]:
• ●Stage 2 disease – Measurements at least yearly • ●Stage 3 disease – Measurements at least every six months • ●Stage 4 disease – Measurements at least every three months • ●Stage 5 disease – Measurements at least monthly • For PTH and alkaline phosphatase measurements, the KDOQI
guidelines recommend: • ●Stage 2 disease – Measurements at least yearly • ●Stage 3 disease – Measurements at least every six months • ●Stage 4 and 5 disease – Measurements at least every three
months Bone biopsy rarely indicated or done
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Lipids
• Current KDIGO guidelines for adults- recommend statins for adults >50 with GFR <60 ml/min/1.73 m2 or post kidney transplant but not those on dialysis (lack of supporting trial data)
• We know the atherosclerotic process begins in childhood • KDIGO recommends baseline measurement of lipids in
children to exclude familial hypertriglyceridemia or rare inherited lipid disorders
• First line treatment: lifestyle modification/dietary ? Fish oil for hypertriglyceridemia- 3 trials in pediatrics showing it reduces TG
• No recommendations for statins in children- lack of trial evidence and outcome data
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Wingen AM et al Randomised multicentre study of a low protein diet on the progression of chronic renal failure in children Lancet 349:1117-1123
Hypertension is an independent risk factor for progression of renal disease in children
Hypertension
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Progression of Renal Disease, According to Blood-Pressure-Control Group
The ESCAPE Trial Group. N Engl J Med 2009;361:1639-1650
ESCAPE trial 2009
Intensive BP target below the 50th percentile compared with conventional 50-95th pc resulted in significantly less reduction in GFR
Endpoint was >50 % decline in GFR or ESKD
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Antihypertensives
• Ideally agents that target RAAS- added benefit of antiproteinuric ACE inhibitors- ESCAPE trial AT Receptor antagonists Combined ACEI andATRA- minor additional effect on BP (4 mmHg) vs monotherapy but significantly increased anti-proteinuric effect 30%. Caution in adults (ONTARGET study high risk CVS disease adults no additional benefit in combination and more adverse events) Aldosterone inhibition- could help with aldosterone escape that occurs with chronic ACEI. Spironolactone not ideal as endocrine effects; can use eplerenone if available.
• Calcium channel blockers- no antiproteinuric effect- only use with ACEI/AT RA in early stages of CKD. May need to be used alone in more advanced CKD because of hyperkalemia
• Beta blockers- metoprolol in older studies equivalent antiproteinuric effect to ACEI.
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Vaccination
• CKD children are at risk of more serious consequences of vaccine preventable infections (including Influenza)
• They should receive all standard immunisations- especially pre-transplant
• Ensure Hep B levels remain adequate –recommended >10 (measure annually). Require adult doses of Hep B vaccine
• Give influenza vaccine annually • HPV (papilloma) virus vaccine important-as at long term increased
risk (especially post transplant) of HPV related cancers. We recently demonstrated adequate initial response in immunosuppressed children (Vaccine 2016)
• Live vaccines should not routinely be given post transplant- there are a few published studies of use with varicella. Use only with extreme caution- should always try to vaccinate pre transplant
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Overall management of the child with CKD
• Close attention to detail, regular follow up
• A multidisciplinary team that includes dietitians, nurses, social workers, psychologists
• Good patient and parent education- information about dialysis and benefits of living kidney donation