MINERAL AND BONE DISORDERS IN CHRONIC KIDNEY DISEASE

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MINERAL AND BONE DISORDERS IN CHRONIC KIDNEY
DISEASE

• PEDRAM.AHMADPOOR
• SHAHID BEHESHTI MEDICAL UNIVERSITY

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Normal Bone Metabolic Unit
Low turn over bone disease High turn over bone
disease mixed
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TMV classificationOMOsteomalaciaOFOsteitis
fibrosaAD Adynamic bone diseaseMUDMixed
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Mechanism for 2 HPT in CRF

• Increased intracellular P in remaining proximal
  tubules? suppression of 1-alpha OHase
• Decreased level of 1,25 D3 starts with GFRlt80
• Increased intracellular P starts earlier
  than changes in serum P

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Consequences of 1,25( OH )D3 deficiency

• Increase in PTH level
• Parathyroid cell proliferation ( VDR)
• Decreased bone calcemic response to PTH
• Increased PTH set point ,Decreased CaSR
• Hypocalcemia

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PTH - Calcium set point
PTH
Normal
Uraemia
50
1.25 mmol/l
Ionised Calcium
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Causes of decreased 1,25(OH)D3 synthesis in
renal failure

• Phosphate retention and Hyperphosphatemia
• Renal tissue loss
• Uremic toxins(GSA,Uric acid)
• FGF-23

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Clinical Manifestation of Renal Osteodystrophy

• Bone pain
• Myopathy and muscle weakness
• Pruritis
• Metastatic and extraskeletal calcification
  (vascular soft tissue)
• Arthritis and Periarthritis
• Spontaneous tendon rupture

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rugger jersey spine
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sub-periosteal resorption
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frogleg view loosers zone
AP view loosers zone
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Vascular Calcification in ESRD
Reprinted from London, et al. Nephrol Transpl
Dial. 2003181731-1740. (London, 2003 p. 1733
fig.1)
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Increased Death Risk in CKD Stage 5 with Elevated
Serum Calcium
Adapted from Block GA et al. J Am Soc Nephrol.
2004152208-2218
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K/DOQI Clinical Practice Guidelineson Bone
Metabolism Target Levels
CKD Stage 3 CKD Stage 4 CKD Stage 5 (on dialysis)
P (mg/dL) 2.7 - 4.6 2.7 - 4.6 3.5 - 5.5
Ca (mg/dL) Normal Normal 8.4 - 9.5 Hypercalcemia gt10.2
Intact PTH (pg/mL) 35 - 70 70 - 110 150 - 300
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Prevention and Treatment of Renal Osteodystrophy

• Prevention of Phosphate retention and
  Hyperphosphatemia
• Treatment of Hypocalcemia
• Vit. D analogs
• Calcimimetics
• Parathyroidectomy

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Phosphate binders

• Calcium containing
• CaCO3
• Ca acetate (Phoslo)
• non calcium containing
• Renagel ,Renvela
• lanthanum carbonate (Fosrenol)
• Mg
• Al

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Al based phosphate binders

• Aluminium toxicities
• Bone
• Neurologic
• hematologic
• Calcium based phosphate binders

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• Plt5.5 Calt9.5 ? Ca containing P binder
• Plt5.5 Ca gt9.5 no P binder
• ( if vascular calc.? non calcium
  containing P binder)
• Pgt5.5 Ca lt9.5 ? Ca containing P binder
• if Ca x P
  lt55
• Pgt5.5 Ca gt9.5 ? non Ca containting P binder
• Ca containing P binders must not be used if
• PTH lt150
• corrected Ca gt10.2
• P binder elemental Ca
  gt1500
• total elemental Ca gt2000

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• A 45 years old man under hemodialysis for 6 years
  due to chronic GN ( wt 70 kg)
• Ca 9.8 mg
• P 5.7 mg
• intact PTH 600 pg/ml
• albumin 3.7 gr/dl
• dialysis 3 x4 h/wk
• What type of bone disease ?
• How do you manage it

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• Diet ? 800-1000 mg P /d
• Phosphate binder?
• Types of Phosphate binder?
• Calcium containing
• CaCO3
• Ca acetate (Phoslo)
• non calcium containing
• Renagel ,Renvela
• lanthanum carbonate (Fosrenol)
• Mg
• Al

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Pgt5.5 Ca gt9.5 ? non Ca containting P binder

• Dose?
• Depends on P blood level
• daily removal
• daily intake /absorption
• binder potency

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• 39 mg P will bind to 1 gr CaCO3
• 45 mg P will bind to 1 gr Ca acetate
• 32 mg to each 400 mg renagel
• 64 mg to each 800 mg renagel tab
• 15.3 mg to each Al tab
• 22.3 mg to 5 ml AlOH3

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• For each gr protein intake consider 10-12mg P
  intake
• Recommended protein intake in HD1-1.2 g/kg
• 70 x 1.2 840 mg /d
• 840 x 60 504 mg /d ? accumulation
• each dialysis P removal ? 700-800 mg
• CAPD? 300 mg/d
• 800 x 3 2400 mg
• 504 x 7 3528
• 3528 2400 1128 /7 160 mg /d ( amount of
  P that must be bound)
• 64 mg to each 800 mg renagel tab
• about 3 renagel tab /d
• Ca-P recheck within 1-4 wks
• PTH q 1-3 months

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How many Ca CO3 pills ?

• 160 mg/39 4 gr CaCO3 ( 8 tab /d)
• elemental Ca 4000 mg x401600 mg
• Ca containing P binders must not be used if
• PTH lt150
• corrected Ca gt10.2
• P binder elemental Ca
  gt1500
• total elemental Ca gt2000
• COMBINATION POLICY

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• Plt5.5 Calt9.5 ? Ca containing P binder
• Plt5.5 Ca gt9.5 no P binder
• ( if vascular calc.? non calcium
  containing P binder)
• Pgt5.5 Ca lt9.5 ? Ca containing P binder
• Pgt5.5 Ca gt9.5 ? non Ca containting P binder

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• Vit D derivatives
• if intact PTH gt300 Ca
  lt9.5 Plt5.5
• Ca x P lt55
• Corrected Ca gt10.2 ?stop
• Corrected Ca 9.5-10.2 ?50 dose reduction
• corrected Ca rising ? dose reduction
• Role of low dose active vitamin D irrespective
  of parathyroid suppression on overall mortality

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Vitamin D
analogs 25(OH) D3 (
calcifediol) 1,25 (OH) D3
(calcitriol, rocaltrol) 1 alpha (OH) D3
( alphacalcidiol ,one alpha) 1alpha (OH) D2
(doxercalciferol , hectoral) 22 oxa
1,25 (OH) D3 (22 oxacalcitriol
,maxacalcitol) 19 nor 1,25( OH) D2
(paricalcitol , zemplar) 24,25(OH)D3
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• Cinacalcet
• indicated in all pts with intact PTH gt300 and Ca
  gt8.4
• (decrease parathyroidectomy,cardivascular
  hospitalizations,Fx)
• Hyperphosphatemia is not containdication
• starting dose 30 mg/d ?180 q4wks
• cinacalcet must not be started if Calt8.4
• during Tx ? Ca lt7.4 ?stop
• 7.4-8.4? adding
  vit d and /calcium if P lt5.5
• So if Ca lt9.5 and P lt5.5 and Ca x P lt55
  PTHgt300? start with vit.D derivative

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• 28 cinacalcet 400,000 toman
• Renagel 400 mg 1980 toman
• AlOH3
• Increasing dialysis
• parathyroidectomy

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How can we calculate daily protein intake

• CRF 6.25 ( urine urea nitrogen nonurea
  nitrogen) proteinuria if gt 5 gr/d
• nonurea nitrogen 30mg/kg

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How can we calculate daily protein intake

• HD (anuric )
• PCR 0.22 0.86 x delta BUN
• Interval
• BUN before dialysis 70
• BUN after diaysis 30
• interval 44
• 0.86 x 40 34/44
  0.78 gr/kg/d

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• Urinary urea nitrogen
  (g)  x  150   anuric PCR        
       ID interval (hrs)  x  weight
  (kg)

  PD PCR  6.25  x (Urea appearance  1.810.0
31x lean body weight, kg)