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MINERAL AND BONE DISORDERS IN CHRONIC KIDNEY DISEASE

MINERAL AND BONE DISORDERS IN CHRONIC KIDNEY DISEASE. PEDRAM.AHMADPOOR SHAHID BEHESHTI MEDICAL UNIVERSITY. Normal Bone Metabolic Unit. Low turn over bone disease High turn over bone disease mixed.

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MINERAL AND BONE DISORDERS IN CHRONIC KIDNEY DISEASE

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  1. MINERAL AND BONE DISORDERS IN CHRONIC KIDNEY DISEASE PEDRAM.AHMADPOOR SHAHID BEHESHTI MEDICAL UNIVERSITY

  2. Normal Bone Metabolic Unit Low turn over bone disease High turn over bone disease mixed

  3. TMV classificationOM=OsteomalaciaOF=OsteitisfibrosaAD= Adynamic bone diseaseMUD=Mixed

  4. 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 GFR<80 Increased intracellular P starts earlier than changes in serum P

  5. 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

  6. PTH - Calcium set point PTH Normal Uraemia 50% 1.25 mmol/l Ionised Calcium

  7. 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

  8. 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

  9. rugger jersey spine

  10. sub-periosteal resorption

  11. frogleg view looser’s zone AP view looser’s zone

  12. Vascular Calcification in ESRD Reprinted from: London, et al. Nephrol Transpl Dial. 2003;18:1731-1740. (London, 2003 p. 1733 fig.1)

  13. Increased Death Risk in CKD Stage 5 with Elevated Serum Calcium Adapted from Block GA et al. J Am Soc Nephrol. 2004;15:2208-2218

  14. K/DOQI™ Clinical Practice Guidelineson Bone Metabolism Target Levels

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

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

  17. Al based phosphate binders • Aluminium toxicities Bone Neurologic hematologic • Calcium based phosphate binders

  18. P<5.5 Ca<9.5  Ca containing P binder • P<5.5 Ca >9.5 no P binder ( if vascular calc. non calcium containing P binder) • P>5.5 Ca <9.5  Ca containing P binder if Ca x P <55 • P>5.5 Ca >9.5  non Ca containting P binder • Ca containing P binders must not be used if: PTH <150 corrected Ca >10.2 P binder elemental Ca >1500 total elemental Ca >2000

  19. 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

  20. 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

  21. P>5.5 Ca >9.5  non Ca containting P binder • Dose? • Depends on P blood level • daily removal • daily intake /absorption • binder potency

  22. 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

  23. For each gr protein intake consider 10-12mg P intake • Recommended protein intake in HD=1-1.2 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

  24. How many Ca CO3 pills ? • 160 mg/39= 4 gr CaCO3 ( 8 tab /d) elemental Ca = 4000 mg x40%=1600 mg Ca containing P binders must not be used if: PTH <150 corrected Ca >10.2 P binder elemental Ca >1500 total elemental Ca >2000 COMBINATION POLICY

  25. P<5.5 Ca<9.5  Ca containing P binder • P<5.5 Ca >9.5 no P binder ( if vascular calc. non calcium containing P binder) • P>5.5 Ca <9.5  Ca containing P binder • P>5.5 Ca >9.5  non Ca containting P binder

  26. Vit D derivatives if intact PTH >300 & Ca <9.5 & P<5.5 & Ca x P <55 Corrected Ca >10.2 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

  27. 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

  28. Cinacalcet • indicated in all pts with intact PTH >300 and Ca >8.4 (decrease parathyroidectomy,cardivascular hospitalizations,Fx) Hyperphosphatemia is not containdication starting dose 30 mg/d 180 q4wks cinacalcet must not be started if Ca<8.4 during Tx  Ca <7.4 stop 7.4-8.4 adding vit d and /calcium if P <5.5 So if Ca <9.5 and P <5.5 and Ca x P <55 +PTH>300 start with vit.D derivative

  29. 28 cinacalcet = 400,000 toman • Renagel 400 mg= 1980 toman • AlOH3 • Increasing dialysis • parathyroidectomy

  30. How can we calculate daily protein intake • CRF= 6.25 ( urine urea nitrogen + nonurea nitrogen) + proteinuria if > 5 gr/d nonurea nitrogen =30mg/kg

  31. 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

  32. Urinary urea nitrogen (g)  x  150   anuric PCR+    ———————————————         ID interval (hrs)  x  weight (kg)   PD: PCR = 6.25  x (Urea appearance + 1.81+[0.031x lean body weight, kg])

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