Course Outline <ul><li>Chapter 1 Kidney and  Hormone  Function </li></ul><ul><li>Chapter 2 SHPT and Chronic Kidney  Failur...
Chapter 1 Outline: Kidney and  Hormone Function <ul><li>Kidney function and hormone production </li></ul><ul><li>Vitamin D...
Kidney Function <ul><li>Excretion </li></ul><ul><ul><li>Excess fluid </li></ul></ul><ul><ul><li>Mineral balance </li></ul>...
Kidney Function <ul><li>Endocrine </li></ul><ul><ul><li>Erythropoeitin - stimulates blood cell production </li></ul></ul><...
Vitamin D Hormone Receptors (VDR) <ul><li>A protein located in the nucleus of the cell  </li></ul><ul><li>Active D hormone...
Ca 2+ PO 4 Intestine PO 4 Ca 2+ Kidney D hormone Blood Ca 2+ (& PO 4 ) Bone Osteoclast X Parathyroid Gland
Vitamin D Receptors (VDR) are Spread Throughout the Body Reproductive   Organs Kidneys Intestines Bones Immune   System Sk...
Kidney Failure Mortality Rates 2001 USRDS Annual Report
Kidney Failure Mortality Rates 2001 USRDS Annual Report
PTH is Directly Related to Mortality Chertow et al, ASN Renal Week Abstracts
Chapter 1 Review Questions <ul><li>1. What are some of the actions D hormone is responsible for? </li></ul><ul><ul><li>a. ...
Chapter 1 Review Answers <ul><li>1. What are some of the actions D hormone is responsible for? </li></ul><ul><ul><li>a.  P...
Chapter 2 Outline:  SHPT and Chronic Kidney Failure   <ul><li>Causes of SHPT </li></ul><ul><li>Progression of SHPT </li></...
Causes of SHPT in Chronic Kidney Failure <ul><li>D hormone deficiency </li></ul><ul><li>Hypocalcemia </li></ul><ul><li>Pho...
When SHPT Begins Martinez I, Saracho R, Montenegro J, Llach F: A deficit of calcitriol synthesis may not be the initial fa...
Normal Parathyroid Gland Physiology <ul><li>Make, store and release parathyroid hormone </li></ul><ul><li>Regulate serum c...
Progression of Parathyroid Gland Pathology with CKD <ul><li>Hypertrophy </li></ul><ul><li>Hyperplasia </li></ul><ul><ul><l...
Side Effects of Elevated PTH <ul><li>Cardiovascular </li></ul><ul><ul><li>Left ventricular hypertrophy </li></ul></ul><ul>...
Side Effects of Elevated PTH <ul><li>Extraosseous calcifications “calciphylaxis” </li></ul><ul><li>Pruritis </li></ul><ul>...
Side Effects of Elevated PTH <ul><li>Corneal-conjunctival calcification </li></ul><ul><li>Skeletal deformities, retardatio...
Electron Beam Computed Tomography (EBCT) Scan <ul><li>New noninvasive tool </li></ul><ul><li>Allows highly sensitive quant...
EBCT Scans Reveal Coronary Artery Calcification in a Dialysis Patient Yellow indicates calcium deposition  Slide courtesy ...
Mitral Valve Calcification in a Dialysis Patient Scan courtesy of P. Raggi.
Calcification of the Lung Sanders C, et al.  Am J Roentgenol.  1987;149:881-887. Kuzela DC, et al.  Am J Pathol.  1977;86:...
Cutaneous/Subcutaneous Calcification Slide courtesy of H. Malluche.
Chapter 2 Review Question <ul><li>1 .  Why is an elevated PTH a concern?  </li></ul><ul><ul><ul><li>a.  It leads to bone d...
Chapter 2 Review Answer <ul><li>1.  Why is an elevated PTH a concern?  </li></ul><ul><li>d.  All of the above </li></ul>
Chapter 3 Outline:  Bone Basics <ul><li>Bone function </li></ul><ul><li>Bone cell types </li></ul><ul><li>D hormone and bo...
Bone Function <ul><li>Support and movement of the body </li></ul><ul><li>Protection of internal organs </li></ul><ul><li>M...
Bone Bone-lining cells Osteoblasts Osteoclasts Osteocytes
Bone
Osteo b lasts <ul><li>Small, bone- b uilder cells that secrete collagen fibers </li></ul><ul><li>Precipitate calcium and p...
Osteoblasts <ul><li>Affected by elevated PTH levels and  D hormone deficiency </li></ul><ul><li>Osteoblast activity can be...
Osteocytes <ul><li>Mature bone cells - mature osteoblasts that are embedded in the bone matrix </li></ul><ul><li>No longer...
Osteo c lasts <ul><li>Large, irregularly shaped, multinuclear cells that  c onsume bone with enzymes </li></ul><ul><li>By ...
Osteoclasts <ul><li>Activity is increased by PTH, D hormone, and thyroid hormone </li></ul><ul><li>Many other local growth...
Bone Turnover <ul><li>A term used to describe the interaction between various hormones and bone formation and resorption <...
Role of  D Hormone in Bone Remodeling <ul><li>D hormone stimulates formation of osteoblasts from osteoprogenitor cells </l...
Development of Renal Bone Disease Core Curriculum for Nephrology Nurses , 1998    GFR    D hormone metabolism    Plasma...
Renal Osteodystrophy
Effects of SHPT on Bone <ul><li>Increases osteoclast activity increasing bone resorption </li></ul><ul><li>Increase bone w...
Chapter 3 Review Question <ul><li>1.  What are the two categories of bone disease we see in renal patients and what typica...
Chapter 3 Review Answer <ul><li>1.  What are the two categories of bone disease we see in renal patients and what typicall...
Chapter 4 Outline:  Vitamin D Hormone Treatment for SHPT <ul><li>Treatment option for SHPT </li></ul><ul><li>Pharmacokinet...
Percentage of New Chronic Dialysis Patients Treated with D Hormone Therapy* *2001 USRDS Annual Report Treated with D hormo...
Treatment Option for SHPT – Vitamin D Hormone Therapy <ul><li>Calcitriol </li></ul><ul><ul><li>Rocaltrol ®  - Oral </li></...
Treatment Option for SHPT  IV Vitamin D Hormone Therapy* *No Clinical Significance NO NO NO Removed by HD? High High High ...
Summary <ul><li>The development of secondary hyperparathyroidism (SHPT) in patients with chronic kidney disease begins ear...
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Bone Care Basics (CRF)

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  • Welcome to this Continuing Education Program. Thank you for taking the time to participate in this program on Bone Care Basics. The management of bone disease in the chronic renal failure population is an important goal for renal professionals. It is important to realize that you have the power to effect the lives of your patients by aiding in the management, and hopefully, by eventually preventing the devastating effects of Bone Disease. With the publication of the KDOQI Bone and Mineral Metabolism Guidelines there are standards for the management of SHPT. The purpose of this course is to provide basic information on secondary hyperparathyroidism and renal bone disease.
  • Bone Care Basics (CRF)

    1. 2. Course Outline <ul><li>Chapter 1 Kidney and Hormone Function </li></ul><ul><li>Chapter 2 SHPT and Chronic Kidney Failure </li></ul><ul><li>Chapter 3 Bone Basics </li></ul><ul><li>Chapter 4 Vitamin D Treatment for SHPT </li></ul><ul><li>Appendix </li></ul>
    2. 3. Chapter 1 Outline: Kidney and Hormone Function <ul><li>Kidney function and hormone production </li></ul><ul><li>Vitamin D hormone: receptors and function </li></ul><ul><li>Parathyroid feedback mechanism </li></ul><ul><li>Vitamin D hormone, PTH and kidney failure </li></ul><ul><li>PTH, SHPT and mortality </li></ul>
    3. 4. Kidney Function <ul><li>Excretion </li></ul><ul><ul><li>Excess fluid </li></ul></ul><ul><ul><li>Mineral balance </li></ul></ul><ul><ul><ul><li>Calcium, phosphorus, potassium, sodium, chloride </li></ul></ul></ul><ul><ul><li>Metabolic toxins </li></ul></ul><ul><ul><ul><li>BUN, creatinine </li></ul></ul></ul>
    4. 5. Kidney Function <ul><li>Endocrine </li></ul><ul><ul><li>Erythropoeitin - stimulates blood cell production </li></ul></ul><ul><ul><li>Renin-angiotension - blood pressure control </li></ul></ul><ul><ul><li>D hormone - </li></ul></ul><ul><ul><ul><li>Calcium/phosphorus balance and bone metabolism </li></ul></ul></ul><ul><ul><ul><li>Effect on various other organs with vitamin D hormone receptors (VDR) </li></ul></ul></ul>
    5. 6. Vitamin D Hormone Receptors (VDR) <ul><li>A protein located in the nucleus of the cell </li></ul><ul><li>Active D hormone must bind to the VDR, stimulate the VDR, so an action can take place on the target tissue </li></ul><ul><li>Active D hormone stimulates the VDR on the parathyroid gland to cease production of PTH </li></ul>
    6. 7. Ca 2+ PO 4 Intestine PO 4 Ca 2+ Kidney D hormone Blood Ca 2+ (& PO 4 ) Bone Osteoclast X Parathyroid Gland
    7. 8. Vitamin D Receptors (VDR) are Spread Throughout the Body Reproductive Organs Kidneys Intestines Bones Immune System Skin Bone Marrow Pancreas Parathyroid Glands
    8. 9. Kidney Failure Mortality Rates 2001 USRDS Annual Report
    9. 10. Kidney Failure Mortality Rates 2001 USRDS Annual Report
    10. 11. PTH is Directly Related to Mortality Chertow et al, ASN Renal Week Abstracts
    11. 12. Chapter 1 Review Questions <ul><li>1. What are some of the actions D hormone is responsible for? </li></ul><ul><ul><li>a. PTH suppression and bone mineralization </li></ul></ul><ul><ul><li>b. Adequate hemoglobin production </li></ul></ul><ul><ul><li>c. Good potassium and phosphorus balance </li></ul></ul><ul><ul><li>d. Adequate hydration </li></ul></ul><ul><li>2. D hormone deficiency contributes to what? </li></ul><ul><li>a. Anemia of chronic disease </li></ul><ul><li>b. Autoimmune disorders and hepatitis </li></ul><ul><li>c. Secondary hyperparathyroidism </li></ul><ul><li>d. Lymphogenesis </li></ul>
    12. 13. Chapter 1 Review Answers <ul><li>1. What are some of the actions D hormone is responsible for? </li></ul><ul><ul><li>a. PTH suppression and bone mineralization </li></ul></ul><ul><li>2. D hormone deficiency contributes to what? </li></ul><ul><li>c. Secondary hyperparathyroidism </li></ul>
    13. 14. Chapter 2 Outline: SHPT and Chronic Kidney Failure <ul><li>Causes of SHPT </li></ul><ul><li>Progression of SHPT </li></ul><ul><li>Effects of SHPT </li></ul>
    14. 15. Causes of SHPT in Chronic Kidney Failure <ul><li>D hormone deficiency </li></ul><ul><li>Hypocalcemia </li></ul><ul><li>Phosphorus retention </li></ul><ul><li>Acid-Base balance </li></ul><ul><li>Diminished degradation of PTH by kidney </li></ul><ul><li>Autonomous parathyroid nodules </li></ul>
    15. 16. When SHPT Begins Martinez I, Saracho R, Montenegro J, Llach F: A deficit of calcitriol synthesis may not be the initial factor in the pathogenesis of secondary hyperparathyroidism. Nephrol Dial Transplant 11 Suppl 3:22-28, 1996.
    16. 17. Normal Parathyroid Gland Physiology <ul><li>Make, store and release parathyroid hormone </li></ul><ul><li>Regulate serum calcium, D hormone and phosphorus levels </li></ul><ul><li>Vitamin D receptors (VDR) and calcium receptors are present on the parathyroid gland and help regulate parathyroid hormone production </li></ul>
    17. 18. Progression of Parathyroid Gland Pathology with CKD <ul><li>Hypertrophy </li></ul><ul><li>Hyperplasia </li></ul><ul><ul><li>Diffuse </li></ul></ul><ul><ul><li>Nodular </li></ul></ul><ul><li>Down-regulation of vitamin D receptors (VDR) </li></ul><ul><ul><li>Decreased D hormone levels </li></ul></ul><ul><ul><li>Low dietary calcium </li></ul></ul><ul><ul><li>Hypocalcemia </li></ul></ul><ul><ul><li>Increasingly non-responsive to calcium and D hormone levels </li></ul></ul>
    18. 19. Side Effects of Elevated PTH <ul><li>Cardiovascular </li></ul><ul><ul><li>Left ventricular hypertrophy </li></ul></ul><ul><ul><li>Myocardial fibrosis </li></ul></ul><ul><ul><li>Hypertension </li></ul></ul><ul><ul><li>Calcification in the cardiac and peripheral vascular systems </li></ul></ul><ul><li>Immune dysfunction </li></ul>Bro S, Olgaard K. Effects of Excess PTH on Nonclassical Target Organs. AJKD 1997.
    19. 20. Side Effects of Elevated PTH <ul><li>Extraosseous calcifications “calciphylaxis” </li></ul><ul><li>Pruritis </li></ul><ul><li>Bone pain and fractures/altered bone metabolism </li></ul><ul><li>Pain and swelling in and around joints </li></ul><ul><li>Muscle weakness </li></ul><ul><li>Spontaneous tendon rupture </li></ul>Bro S, Olgaard K. Effects of Excess PTH on Nonclassical Target Organs. AJKD 1997.
    20. 21. Side Effects of Elevated PTH <ul><li>Corneal-conjunctival calcification </li></ul><ul><li>Skeletal deformities, retardation of growth </li></ul><ul><li>Anemia </li></ul><ul><li>Impotence </li></ul><ul><li>Altered platelet function </li></ul><ul><li>Insulin resistance </li></ul>Bro S, Olgaard K. Effects of Excess PTH on Nonclassical Target Organs. AJKD 1997.
    21. 22. Electron Beam Computed Tomography (EBCT) Scan <ul><li>New noninvasive tool </li></ul><ul><li>Allows highly sensitive quantification of calcium deposits in living patients </li></ul><ul><li>Allows earlier diagnosis of calcification </li></ul><ul><li>Can be used for whole body scanning </li></ul>
    22. 23. EBCT Scans Reveal Coronary Artery Calcification in a Dialysis Patient Yellow indicates calcium deposition Slide courtesy of P. Raggi. Bone
    23. 24. Mitral Valve Calcification in a Dialysis Patient Scan courtesy of P. Raggi.
    24. 25. Calcification of the Lung Sanders C, et al. Am J Roentgenol. 1987;149:881-887. Kuzela DC, et al. Am J Pathol. 1977;86:403-424. Slide courtesy of E. Slatopolsky. Calcified Noncalcified
    25. 26. Cutaneous/Subcutaneous Calcification Slide courtesy of H. Malluche.
    26. 27. Chapter 2 Review Question <ul><li>1 . Why is an elevated PTH a concern? </li></ul><ul><ul><ul><li>a. It leads to bone disease. </li></ul></ul></ul><ul><li>b. It leads to cardiac disease. </li></ul><ul><li>c. It causes immunosuppression. </li></ul><ul><li>d. All of the above </li></ul>
    27. 28. Chapter 2 Review Answer <ul><li>1. Why is an elevated PTH a concern? </li></ul><ul><li>d. All of the above </li></ul>
    28. 29. Chapter 3 Outline: Bone Basics <ul><li>Bone function </li></ul><ul><li>Bone cell types </li></ul><ul><li>D hormone and bone remodeling </li></ul><ul><li>Bone turnover and renal bone disease </li></ul>
    29. 30. Bone Function <ul><li>Support and movement of the body </li></ul><ul><li>Protection of internal organs </li></ul><ul><li>Mineral storage </li></ul><ul><li>Production of blood cells </li></ul>
    30. 31. Bone Bone-lining cells Osteoblasts Osteoclasts Osteocytes
    31. 32. Bone
    32. 33. Osteo b lasts <ul><li>Small, bone- b uilder cells that secrete collagen fibers </li></ul><ul><li>Precipitate calcium and phosphorus from the blood to mineralize the bones, the creation of the osteocyte </li></ul><ul><li>Located at sites where bone remodeling needs to occur </li></ul>
    33. 34. Osteoblasts <ul><li>Affected by elevated PTH levels and D hormone deficiency </li></ul><ul><li>Osteoblast activity can be indirectly measured by alkaline phosphatase </li></ul>
    34. 35. Osteocytes <ul><li>Mature bone cells - mature osteoblasts that are embedded in the bone matrix </li></ul><ul><li>No longer able to form bone actively </li></ul><ul><li>Maintain bone matrix </li></ul><ul><li>Play an active role in releasing calcium into the blood </li></ul>
    35. 36. Osteo c lasts <ul><li>Large, irregularly shaped, multinuclear cells that c onsume bone with enzymes </li></ul><ul><li>By digesting collagen and releasing bone minerals into the bloodstream, osteoclasts erode the bone surface causing small shallow pits or cavities, which are named Howship’s lacunae </li></ul>
    36. 37. Osteoclasts <ul><li>Activity is increased by PTH, D hormone, and thyroid hormone </li></ul><ul><li>Many other local growth factors play an important role in bone remodeling </li></ul><ul><ul><li>Calcitonin inhibits the release of calcium from bone </li></ul></ul><ul><ul><li>D hormone increases intestinal absorption of calcium </li></ul></ul><ul><ul><li>PTH and prolactin stimulte D hormone production </li></ul></ul><ul><ul><li>Interleukin-6 stimulates osteoclast development </li></ul></ul><ul><ul><li>Estrogen inhibits bone resorption </li></ul></ul>
    37. 38. Bone Turnover <ul><li>A term used to describe the interaction between various hormones and bone formation and resorption </li></ul><ul><li>“ High Bone Turnover” vs “Low Bone Turnover” disease </li></ul><ul><ul><li>High Bone Turnover results in a decrease in bone density with porous and coarse-fibered bone </li></ul></ul><ul><ul><li>Low Bone Turnover results in non-uniform bone remodeling </li></ul></ul>
    38. 39. Role of D Hormone in Bone Remodeling <ul><li>D hormone stimulates formation of osteoblasts from osteoprogenitor cells </li></ul><ul><li>Activation of D hormone receptor on osteoblast enhances synthesis of osteocalcin, a requirement for new bone formation </li></ul><ul><li>D hormone may also indirectly stimulate osteoclast activity </li></ul>
    39. 40. Development of Renal Bone Disease Core Curriculum for Nephrology Nurses , 1998  GFR  D hormone metabolism  Plasma HPO 4  Ca ++ absorption from GI tract  Plasma Ca ++  PTH  osteoclasts Ca ++ & HPO 4 – resorbed from bones OSTEODYSTROPHIES  CaHPO 4 product METASTATIC CALCIFICATIONS
    40. 41. Renal Osteodystrophy
    41. 42. Effects of SHPT on Bone <ul><li>Increases osteoclast activity increasing bone resorption </li></ul><ul><li>Increase bone weakness and pain </li></ul><ul><li>Increase fracture rate </li></ul>
    42. 43. Chapter 3 Review Question <ul><li>1. What are the two categories of bone disease we see in renal patients and what typically is the PTH level? </li></ul><ul><ul><ul><li>a. High turnover bone disease with a low PTH and Low turnover bone disease with a low PTH </li></ul></ul></ul><ul><li>b. Low turnover bone disease with a low PTH and renal osteodystrophy with an elevated PTH </li></ul><ul><li>c. Osteitis fibrosa with a low PTH and adynamic bone disease with an elevated PTH </li></ul><ul><li>d. High turnover bone disease with an elevated PTH and low turnover bone disease with a low PTH </li></ul>
    43. 44. Chapter 3 Review Answer <ul><li>1. What are the two categories of bone disease we see in renal patients and what typically is the PTH level? </li></ul><ul><li>d. High turnover bone disease with an elevated PTH and low turnover bone disease with a low PTH </li></ul>
    44. 45. Chapter 4 Outline: Vitamin D Hormone Treatment for SHPT <ul><li>Treatment option for SHPT </li></ul><ul><li>Pharmacokinetic profiles </li></ul><ul><li>Effective treatment modalities </li></ul>
    45. 46. Percentage of New Chronic Dialysis Patients Treated with D Hormone Therapy* *2001 USRDS Annual Report Treated with D hormone Hemodialysis Patients Peritoneal Dialysis Patients
    46. 47. Treatment Option for SHPT – Vitamin D Hormone Therapy <ul><li>Calcitriol </li></ul><ul><ul><li>Rocaltrol ® - Oral </li></ul></ul><ul><ul><li>Calcijex ® - Injectable </li></ul></ul><ul><ul><li>Calcitriol (generic) – Oral and Injectable </li></ul></ul><ul><li>Doxercalciferol </li></ul><ul><ul><li>Hectorol ® - Oral and Injectable </li></ul></ul><ul><li>Paracalcitol </li></ul><ul><ul><li>Zemplar ™ - Injectable </li></ul></ul>
    47. 48. Treatment Option for SHPT IV Vitamin D Hormone Therapy* *No Clinical Significance NO NO NO Removed by HD? High High High Protein Binding Hepatic Hepatic Hepatic Elimination 5 minutes 5 minutes 8-9 hours Time to max conc. 19±3 16±9 32-37 Half-Life (hr) Calcijex ® calcitriol Zemplar ® paricalcitol Hectorol ® doxercalciferol
    48. 49. Summary <ul><li>The development of secondary hyperparathyroidism (SHPT) in patients with chronic kidney disease begins early in the disease process and has an impact on mortality and morbidity </li></ul><ul><li>Bone disease has a large impact on chronic kidney failure patients </li></ul><ul><li>Vitamin D hormone therapy is recommended for the treatment of SHPT in chronic renal failure patients on dialysis </li></ul>
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