Chronic kidney disease mbd full version.pptx

Chronic kidney bone mineral
Calcium phosphate

1. CKD-MBD BY : Ala’a Shatla Bones of glass ... Hearts of stone

2. Agenda : Overview . Definition. Pathophysiology . Clinical features. KDIGO d iagnosis guidelines of CKD-MBD. Therapeutic target levels. Treatment of CKD-MBD. KDIGO treatment guidelines. Treatment failure and surgical intervention. Conclusion.

3. Overview : 1943: renal osteodystrophy (ROD) : Secondary hyperparathyroidism Osteomalacia Osteosclerosis Osteoporosis 30 following years >>> academic concept with no chance to be applied in the daily clinical management of CKD patients 1970-1980 : PTH assays and bone biopsy >>> diagnosis of ROD useful in clinical practice 2006 : anew term was proposed with abroader scope ….

4. Definition of CKD-MBD: A systemic disorder of mineral and bone metabolism due to CKD manifested by either one or a combination of the following: Abnormalities of calcium, phosphorus, PTH, or vitamin D metabolism. Abnormalities in bone turnover, mineralization, volume, linear growth, or strength. Vascular or other soft-tissue calcification.

5. Back to normal physiology: * PTH action: Increase serum Ca & decrease serum Pi

6. *Active Vit. D action: Increase serum Ca & increase serum Pi

7. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4699443/#:~:text=The%20CKD%2DMBD%20is%20a,those%20with%20CKD%20%5B71%5D

8. *Action of FGF23:   It decreases the expression of NPT2, a sodium-phosphate cotransporter  in the proximal tubule .  Thus , FGF23 decreases the reabsorption of calcium and increases excretion of phosphate .  Klotho

9. *Klotho “The Greek God of fate who spins the thread of life” ageing suppressor gene , encoding a transmembrane protein that forms a complex with the FGF receptor to increase FGF-23 affinity. Expressed principally in the kidney, brain, and parathyroid gland , it is a mandatory cofactor for the actions of FGF-23 within mineral homeostasis. decreased Klotho expression is one of the earliest biomarkers for CKD and continues to decline as GFR falls.

10. Pathogenesis: As kidney function declines, there is a progressive deterioration in mineral homeostasis, with a disruption of normal serum and tissue concentrations of Pi and Ca , and changes in circulating levels of hormones.

11. Beginning in CKD stage 3, the ability of the kidneys to appropriately excrete a phosphate load is diminished, leading to ↑ ↑ Pi , ↑ ↑ PTH , and ↓ ↓ 1,25(OH)2D with associated ↑↑ in the levels of FGF-23 . The conversion of 25(OH)D to 1,25(OH)2D is impaired, reducing intestinal calcium absorption.

12. Pathogenesis of this disorder is complex and it involves a number of feedback loops between the kidney , bone , intestine , parathyroid glands and vasculature .

13. D D

14. Renal osteodystrophy is an alteration of bone morphology in patients with CKD. It is one measure of the skeletal component of the systemic disorder of CKD–MBD that is quantifiable by histomorphometry of bone biopsy. *Definition of renal osteodystrophy :

15. Classification : The spectrum of skeletal abnormalities seen in renal osteodystrophy includes the following: Secondary hyperparathyroidism (SHPT): ↑PTH causes ↑bone resorption and formation (high turnover disease ). Haphazardally organized ,weakened bone results ( osteitis fibrosa cystica ) Adynamic bone disease: paucity of cells with ↓ bone resorption and formation (low turnover) Osteomalacia : defect in mineralization .Generally related to a deficiency of 1,25 (OH)2D but aluminum intoxication and uremic acidosis are also important risk factors . Osteopenia or osteoporosis . Mixed uraemic osteodystrophy : also relatively common as an evolution from one form to another . Other abnormalities with skeletal manifestations (e.g., chronic acidosis , β 2 - microglobulin amyloidosis).

16. *High turn over- Osteitis Fibrosa Cystica

17. *High turn over- Osteitis Fibrosa Cystica

18. *High turn over- Osteitis Fibrosa Cystica

19. *Calcific uraemic arteriolopathy ( caciphylaxis ) Extraskeletal calcification of the  vasculature  increases progressively with declining eGFR . In addition, cardiac valvular , and other soft tissue, calcification is a frequent finding in advanced CKD . Calcification also makes vascular interventions , such as CABG or angioplasty, more challenging.

20. Calcification can occur in both the intimal and medial layers of the vasculature, but medial calcification is considered the more common and major form of calcification in CKD .

21. Imbalance between promotors & inhibitors paves the way for extraosseous calcification.

22. *Clinical features Bone pain, arthralgia, and muscle weakness (esp. proximal). Pruritus (cutaneous calcium phosphate deposition). Bony deformity (e.g. resorption of terminal phalanges. Increased fracture risk (hip fracture risk ~ 5 x in dialysis patients ). Marrow fibrosis contributes to anemia and poor ESA response. Increased risk of soft tissue and vascular calcification: Intimal calcification Medial calcification

23. *Diagnosis of CKD-MBD : 3.1.1 : We recommend monitoring serum levels of calcium, phosphate, PTH, and alkaline phosphatase activity beginning in CKD G3a (1C).In children,We suggest such monitoring beginning in CKD G2 (2D). 3.1.2 : In patients with CKD G3a to G5D, it is reasonable to base the frequency of monitoring serum calcium, phosphate, and PTH on the presence and magnitude of abnormalities, and the rate of progression of CKD (Not graded). Biochemical abnormalities

24. *Reasonable monitoring intervals of serum Ca ,Pi ,PTH ,Alkaline phosphatase according to CKD progression : CKD stage GFR Serum Ca & Pi PTH Alkaline phosphatase Calcidiol 3 30-59 Every 6-12 months Baseline level & CKD progression Baseline Baseline 4 15-29 Every 3-6 months Every 6-12 months Every 6-12 months Baseline 5 & 5D <15 or dialysis Every 1-3 months Every 3-6 months Every 3-6 months Baseline

25. 3.1.3: In patients with CKD G3a to G5D, we suggest that 25-(OH)D ( calcidiol ) levels might be measured, and repeated testing determined by baseline values and therapeutic interventions (Grade 2C recommendation). We suggest that vitamin D deficiency and insufficiency be corrected using treatment strategies recommended for the general population(2C). 3.1.4: In patients with CKD G3a to G5D, we recommend that therapeutic decisions be based on trends rather than on a single laboratory value, taking into account all available CKD–MBD assessments (Grade 1C recommendation). 3.1.5 : In patients with CKD G3a to G5D, we suggest that individual values of serum calcium and phosphate, evaluated together, be used to guide clinical practice rather than the mathematical construct of calcium–phosphate product (Ca × P)(2D) .

26. Bone abnormalities 3.2.1: In patients with CKD G3a–G5D with evidence of CKD-MBD and/or risk factors for osteoporosis, we suggest BMD testing to assess fracture risk if results will impact treatment decisions (2B ). 3.2.2: In patients with CKD G3a–G5D, it is reasonable to perform a bone biopsy if knowledge of the type of renal osteodystrophy will impact treatment decisions (Not Graded). 3.2.3: In patients with CKD G3a–G5D, we suggest that measurements of serum PTH or bone-specific alkaline phosphatase can be used to evaluate bone disease because markedly high or low values predict underlying bone turnover (2B).

27. 3.2.4 : In patients with CKD G3a–G5D, we suggest not to routinely measure bone-derived turnover markers of collagen synthesis (such as procollagen type I C-terminal propeptide ) and breakdown (such as type I collagen cross-linked telopeptide , cross-laps, pyridinoline , or deoxypyridinoline ) (2C ). 3.2.5: We recommend that infants with CKD G2–G5D have their length measured at least quarterly, while children with CKD G2–G5D should be assessed for linear growth at least annually (1B ).

28. Vascular calcification 3.3.1: In patients with CKD G3a–G5D, we suggest that a lateral abdominal radiograph can be used to detect the presence or absence of vascular calcification, and an echocardiogram can be used to detect the presence or absence of valvular calcification , as reasonable alternatives to computed tomography-based imaging (2C). 3.3.2: We suggest that patients with CKD G3a–G5D with known vascular or valvular calcification be considered at highest cardiovascular risk (2A ). It is reasonable to use this information to guide the management of CKD-MBD (Not Graded).

29. Aortic calcification Digital arteries calcification

30. Mitral valve calcification

31. *Therapeutic Target levels Phosphorus (mg/dl) Calcium(mg/dl) PTH ( pg /ml) GFR CKD stage 2.7-4.6 Normal 35-70 30-59 3 2.7-4.6 Normal 70-110 15-29 4 3.5-5.5 8.4-9.5 150-300 <15 or dialysis 5 & 5D

32. Phosphorus (mg/dl) Calcium (mg/dl) PTH ( pg /ml ) CKD stage Normal Normal No numerical target 3 Normal Normal No numerical target 4 Normal Normal No numerical target 5 Lowered toward normal range Normal 2-9 times the upper limit of normal range. 5D

33. Goal : Keep serum Ca2+ and PO4 within the normal range. Keep bone turnover and strength as near normal as possible. Keep serum PTH appropriate to these objectives. Prevent the development of parathyroid hyperplasia. The standard treatment package comprises: Measures to decrease serum PO4: Dietary PO 4 restriction. Oral phosphate binders (prevent absorption). Removal through adequate dialysis. Measures to suppress PTH synthesis and secretion: Calcitriol or vitamin D analogues (e.g. alfacalcidol , paricalcitol ). Calcimimetic agents. Measures to normalize serum Ca 2+: Appropriate calcium intake ±supplementation (including calcium-containing binders). Appropriate vitamin D treatment. Appropriate dialysate concentration. *Treatment of CKD-MBD

34. Therapeutic decisions must based on trends rather than on a single laboratory value .

35. Management of hyperphosphatemia:

36. Restricting phosphorus in the diet to 800 to 1,200 mg per day is the key to controlling serum phosphorus. Dietary restriction

37. B. Removal of phosphorus by dialysis

38. C. Phosphorus binders. *Despite phosphorus dietary restriction and adequate hemodialysis, approximately 90% of dialysis patients continue to need oral phosphorous binders in an effort to control their phosphorus levels. *The use of phosphorus binders may also correlate with longer survival and better nutritional status for patients on maintenance hemodialysis.

39. (1) Aluminum-based binders: Aluminum carbonate and aluminum hydroxide . They are the primary therapy for hyperphosphatemia until the mid-1980’s . No longer used chronically because of the high risk of Aluminum toxicity resulting in (dementia , osteomalacia and anemia) . Usage for short periods is necessary to reduce severely elevated phosphorus and (calcium × phosphorus) products in patients with severe hyperparathyroidism and/or concurrent hypercalcemia. O ral citrate must be avoided in patients taking Aluminum binders as this has been shown to lead to enhanced absorption >>> acute aluminum neurotoxicity. Inexpensive. Very effective. Short term use only.

40. (2) Magnesium based binders: Mg carbonate plus Ca acetate Mg carbonate plus Ca carbonate Inexpensive . Lower calcium load per equivalent phosphate-binding dose . Less hypercalcemia. Need for magnesium monitoring. Dose limited by serum Mg levels and diarrhea. Magnesium-containing binders have at least two potential beneficial effects: (1) magnesium is an anticalcification factor, and it might retard vascular calcification in dialysis patients, although the evidence for this is limited (Spiegel, 2009); (2) mortality tends to be reduced in dialysis patients with higher serum magnesium levels , although it is not clear that magnesium supplementation beyond achievement of physiological serum levels is beneficial .

41. (3) Calcium based binders: Ca acetate & Ca carbonate Useful when some degree of calcium supplementation is desired. Dose titration is limited by KDIGO recommendations that elemental calcium ingestion should generally not exceed 1.5 g per day . A resonable starting dose is 1–2 tablets with each meal. The co-administration of calcium and active vitamin D preparations predisposes up to 50% of patients to hypercalcemia . Dialysis solution calcium concentration should be limited to 2.25 to 2.5 mEq /L.

42. (4) Non- calcium,non -aluminum Lanthanum Carbonate Became available in the United States in 2005. As a trivalent cation, lanthanum binds phosphorus ionically . It is available in 250, 500, 750, and 1,000 mg chewable tablets that may also be crushed. A reasonable starting dose is 500 mg three times per day with upward titration as needed, but not to exceed 1,250 mg three times per day. Advantages : minimally absorbed & lower tablet burden. Disadvantages: expensive & long-term outcome and safety data currently lacking.

43. Sevelamer HCl Non-absorbed, does not Accumulate. Avoids calcium. May slow progression of coronary and aortic calcification. Other beneficial effects: ↓LDL, ↓ urate , ↓inflammation. Expensive. GI intolerance. Large doses needed (average 8 tablets/day). Causes a reduction in serum bicarbonate. Sevelamer hydrochloride ( Renagel ® ), 1 – 3 /800mg tablets with each meal . Sevelamer carbonate Similar to sevelamer HCl . Better GI tolerance. Avoids ↓ bicarbonate. Expensive. Large doses Needed. Sevelamer carbonate ( Renvela ® ), 1 – 3/ 800mg tablets or one 2,400mg powder sachet with each meal. (4) Non- calcium,non -aluminum Sevelamer

44. (5) Iron based binders Sucroferric oxyhydroxide (PA21 or Velphoro ) PA21 is an iron-containing phosphorus binder that contains no calcium or aluminum . PA21 completed Phase 3 clinical trials in hemodialysis patients and was approved for use as a phosphorus binder in the United States in 2013 ( Floege , 2014). It comes as a 500-mg chewable tablet; the starting dose is 1.5 g per day ( 3 tablets per day with meals) with a suggested maximum dose of 3 g per day . In contrast to ferric citrate, which is another iron-based phosphorus binder described next, Velphoro is associated with only minimal oral iron absorption.

45. (5) Iron based binders Ferric citrate Ferric citrate is an iron-based phosphate binder that contains no calcium or aluminum. Ferric citrate has been approved for both CKD and ESKD patients in Japan (Yokoyama, 2014a , 2014b) and was approved in the United States in 2014 based on the results of a Phase 3 52-week clinical trial (Lewis, 2014 ) . Ferric citrate comes as a tablet containing 210 mg ferric iron as 1 g ferric citrate and can be titrated to its maximum dose of 12 tablets/day (2.5 g ferric iron/day ). Patients treated with ferric citrate demonstrated significant improvement in serum iron measures (TSAT, ferritin) in addition to a reduced need for IV iron and reduced need for ESA therapy. Ferric citrate may prove highly effective as dual therapy in hyperphosphatemic patients that require iron repletion. However, in patients where iron loading is a concern, ferric citrate may not be an optimal choice.

46. Use of more than one phosphorus binder. Combined treatment with different types of phosphorus binders may be advantageous and cost effective. Regimens should be individually tailored to each patient. Combinations should take into account the patient’s medication preferences, side effect tolerance, and financial considerations. Total daily exposure to elemental calcium and magnesium should also factor into the choice of agents used. The combination of calcium- and non calcium-based agents may provide target phosphorus control and calcium supplementation without risking excess exposure to calcium .

47. 25-D (25-hydroxycholecalciferol) is synthsized by the liver from cholecalciferol and reflects vitamin stores. These are frequently low in dialysis patients. Several factors likely account for the high incidence of deficiency, including poor sun exposure in ill patients, restriction of vitamin D–fortified dairy products for purposes of phosphorus control. Measures to suppress PTH : Vit D analogues & Calcimimetics

48. Active vitamin D (calcitriol) and vitamin D receptor agonists suppress serum PTH in a dose-dependent fashion . The higher the pretreatment PTH, the larger the dose required to suppress PTH into the desired range. The medications are usually given intrave-nously during each dialysis, but can be given orally, usually two to three times a week.

49. Calcitriol Biologically active VDR agonist . a synthetic form of the natural compound. Effectively suppress SHPT. usually started at 1–2 mcg IV with each hemodialysis or orally two to three times per week. Reduces abnormal high bone turnover. Vit D analogues

50. Alfacalcidol Supress SHPT similar to calcitriol. Requires activation in liver to produce active 1,25-D . Induces significant elevation of serum P >>> needs phosphate binder use .

51. Paricalcidol Biologically active VDR agonist . H as less hypercalcemic and hyperphosphatemic actions in animal studies. The initial dose in mcg per dialysis treatment can be estimated by dividing the pretreatment iPTH by 120. An oral formulation is also available for patients with CKD or patients on peritoneal dialysis. A starting dose of 1 mcg daily or 2 mcg three times a week can be administered to patients with an iPTH less than or equal to 500 pg /mL (53 pmol /L). An initial dose of 2 mcg daily or 4 mcg three times a week can be started in patients with iPTH greater than 500 pg /mL (53 pmol /L ).

52. Calcimimetics Bind to the calcium sensing receptor on the parathyroid gland, making it more responsive to the ambient ionized calcium; this results in suppression of PTH, a marked decrease in serum calcium, and a slight decrease in serum phosphorus. Cinacalcet ( Sensipar ) , the only calcimimetic presently available, is a pill available in 30, 60, and 90 mg. The initial dose of cinacalcet should be 30 mg daily regardless of serum PTH, and should not be initiated if the calcium is <8.4 mg/ dL . The dose should be increased by 30-mg increments to a maximum of 180 mg per day, based on monthly or quarterly PTH results, provided the corrected calcium is >7.8 mg/ dL .

53. * Side effects : Hypocalcemia is rarely symptomatic and can be managed by addition of 500 to 1,000 mg of elemental calcium on an empty stomach, an increase or addition of active vitamin D, or an increase in dialysate calcium to 3.0 or 3.5 mEq /L ( 1.5 or 1.75 mM ). Other major side effects of cinacalcet are nausea and vomiting, which occur in up to 30% of patients, and rash. *Indications: Indicated in all patients with IPTH >700 and serum Ca > 8.4 . Must not be taken if Ca < 8.4. Repeat PTH level after 4 months. Cinacalcet therapy if PTH decrease more than 30%, so good response to cinacalcet .

54. Measures to normalize serum Ca 2+: The normal range for serum calcium is 8.4 to 10.2 mg/ dL (2.10–2.55 mmol /L), and the KDIGO guidelines recommend maintaining predialysis total calcium within this range. In hypoalbuminemia , the total calcium reported from the laboratory can be corrected by using the equation : Corrected calcium(in mg/ dL ) = total calcium +{0.8 × ( 4.0 −albumin [in g/ dL ])} KDIGO does not recommend the routine use of albumin-corrected calcium.

55. Hypercalcemia is usually due to excessive use of calcium-based binders and/or to use of vitamin D receptor agonists that increase gut calcium absorption. Patients with low PTH appear to have the highest range of serum calcium, which may reflect adynamic bone disease and poor ability of bone to buffer calcium . Advanced hyperparathyroidism associated with a large mass of autonomous parathyroid tissue can rarely result in hypercalcemia in the absence of oral calcium administration or the use of active vitamin D. This is referred to as tertiary hyperparathyroidism *Hypercalcemia : Low levels of total uncorrected calcium are often due to a low serum albumin . A low corrected calcium may be due to poor gastrointestinal absorption of calcium due to vitamin D deficiency, severe hyperphosphatemia , or use of the calcimimetic agent, cinacalcet . *Hypocalcemia:

56. *Dialysis solution calcium concentration: Dialysis solution calcium should generally be 2.5 mEq /L (1.25 mM ) in most patients on chronic hemodialysis, This will usually maintain a neutral calcium balance. Peritoneal dialysis fluid calcium concentration should be 2.5 mEq /L (1.25 mM ) in most patients.

57. * KDIGO treatment guidelines : Treatment of CKD-MBD targeted at lowering high serum Po4 and maintaining serum Ca 4.1.1: In patients with CKD G3a–G5D, treatments of CKD-MBD should be based on serial assessments of phosphate ,calcium , and PTH levels, considered together (Not Graded ). 4.1.2: In patients with CKD G3a–G5D, we suggest lowering elevated phosphate levels toward the normal range (2C ). 4.1.3 : In adult patients with CKD G3a–G5D, we suggest avoiding hypercalcemia (2C). In children with CKD G3a–G5D,we suggest maintaining serum calcium in the age appropriate normal range (2C ).

58. 4.1.6: In adult patients with CKD G3a–G5D receiving phosphate-lowering treatment, we suggest restricting the dose of calcium-based phosphate binders (2B). In children with CKD G3a–G5D, it is reasonable to base the choice of phosphate-lowering treatment on serum calcium levels (Not Graded). 4.1.7: In patients with CKD G3a-G5D, we recommend avoiding the long-term use of aluminum-containing phosphate binders and, in patients with CKD G5D, avoiding dialysate aluminum contamination to prevent aluminum intoxication (1C). 4.1.5 : In patients with CKD G3a-G5D, decisions about phosphate lowering treatment should be based on progressively or persistently elevated serum phosphate (Not Graded). 4.1.4: In patients with CKD G5D, we suggest using a dialysate calcium concentration between 1.25 and 1.50 mmol /l(2.5 and 3.0 mlEq /l) (2C ).

59. 4.1.8: In patients with CKD G3a–G5D, we suggest limiting dietary phosphate intake in the treatment of hyperphosphatemia alone or in combination with other treatments (2D). It is reasonable to consider phosphate source(e.g., animal, vegetable, additives) in making dietary recommendations (Not Graded). 4.1.9 : In patients with CKD G5D, we suggest increasing dialytic phosphate removal in the treatment of persistent hyperphosphatemia (2C).

60. Treatment of abnormal PTH levels in CKD-MBD: 4.2.1: In patients with CKD G3a–G5 not on dialysis, the optimal PTH level is not known. However, we suggest that patients with levels of intact PTH progressively rising or persistently above the upper normal limit for the assay be evaluated for modifiable factors, including hyperphosphatemia, hypocalcemia, high phosphate intake, and vitamin D deficiency (2C). 4.2.2 : In adult patients with CKD G3a–G5 not on dialysis, we suggest that calcitriol and vitamin D analogs not be routinely used (2C). It is reasonable to reserve the use of calcitriol and vitamin D analogs for patients with CKD G4–G5 with severe and progressive hyperparathyroidism (Not Graded). In children, calcitriol and vitamin D analogs may be considered to maintain serum calcium levels in the age appropriate normal range (Not Graded).

61. 4.2.3: In patients with CKD G5D, we suggest maintaining iPTH levels in the range of approximately 2 to 9 times the upper normal limit for the assay (2C). We suggest that marked changes in PTH levels in either direction within this range prompt an initiation or change in therapy to avoid progression to levels outside of this range (2C). 4.2.4: In patients with CKD G5D requiring PTH-lowering therapy, we suggest calcimimetics , calcitriol, or vitamin D analogs , or a combination of calcimimetics with calcitriol or vitamin D analogs (2B). 4.2.5: In patients with CKD G3a–G5D with severe hyperparathyroidism (HPT) who fail to respond to medical or pharmacological therapy, we suggest parathyroidectomy (2B).

62. Treatment of bone with bisphosphonates, other osteoporosis medications, and growth hormone 4.3.1: In patients with CKD G1–G2 with osteoporosis and/or high risk of fracture, as identified by World Health Organization criteria, we recommend management as for the general population (1A). 4.3.2: In patients with CKD G3a–G3b with PTH in the normal range and osteoporosis and/or high risk of fracture, as identified by World Health Organization criteria, we suggest treatment as for the general population (2B).

63. 4.3.3: In patients with CKD G3a–G5D with biochemical abnormalities of CKD-MBD and low BMD and/or fragility fractures, we suggest that treatment choices take into account the magnitude and reversibility of the biochemical abnormalities and the progression of CKD, with consideration of a bone biopsy(2D). 4.3.4: In children and adolescents with CKD G2–G5D and related height deficits, we recommend treatment with re- combinant human growth hormone when additional growth is desired, after first addressing malnutrition and biochemical abnormalities of CKD-MBD (1A).

64. Adynamic bone disease (ABD) : Adynamic bone disease is characterized by reduced osteoblast and osteoclast number and low or absent bone formation rate. The osteoid thickness is normal or reduced, distinguishing it from osteomalacia . Associated laboratory findings may include an iPTH less than 100 pg /mL (11 pmol /L), low serum bone-specific alkaline phosphatase, and occasionally , a slightly elevated serum ionized calcium level.

65. Miscellaneous therapies While these agents can increase bone density in osteoporosis, they have not been adequately tested or shown to be efficacious in dialysis patients . Bisphosphonates decrease bone resorption by inhibiting osteoclasts, this reduction in bone turnover may be deleterious in dialysis patients , creating a form of adynamic bone disease. Generally, these agents should not be used in dialysis patients . A synthetic form of PTH(1-34), this polypeptide induces a marked increase in bone density in osteoporotic patients when administered as a daily subcutaneous injection. It has not been tested in dialysis patients, but may be of value in the treatment of adynamic bone disease, as PTH levels usually are low in this disorder. Bisphosphonates : B.Teriparatide :

66. * Treatment failure & surgical intervention: Treatment failure includes : Dialysis patients with tertiary hyperparathyroidism ,which is defined as elevated PTH levels and spontaneous hypercalcemia . Patients with persistent and progressive elevations of serum PTH that cannot be lowered to levels <300pg/ml despite treatment with vitamin D analogs and Cinacalcet (180 mg/day ).

67. Parathyroidectomy : Despite aggressive efforts to control PTH levels , surgical parathyroidectomy (PTX) continues to be necessary in those patients with severe hyperparathyroidism . 1. Severe progressive symptomatic osteitis fibrosa (skeletal pain and/or fractures) despite adequate medical management, including serum phosphorus control and calcitriol therapy. 2. Very high levels of PTH plus any of the following: Persistent hypercalcemia if other causes have been excluded. Severe intractable pruritus. Persistent severe soft tissue calcification despite attempts to control the serum phosphorus level. Idiopathic disseminated skin necrosis ( calciphylaxis ). Incapacitating arthritis, periarthritis , and spontaneous tendon ruptures.

68. *Conclusion : Disorders of mineral and bone metabolism are common sequelae of CKD, with Secondary hyperparathyroidism encompassing most of the biochemical abnormalities. There is an increased risk of all-cause and cardiovascular mortality in patients with disorders of mineral metabolism. Among dialysis patients with elevated PTH levels, a stepped approach to the management of hyperparathyroidism and bone mineral abnormalities is recommended.

69. This approach requires a complex balance of four medications, namely calcium-containing binders, non-calcium-containing binders, calcimimetics , and either calcitriol or synthetic vitamin D analogs. Most current ABD cases result from excessive suppression of the parathyroid glands due to increased and earlier use of vitamin D analogs and calcium-containing phosphate binders. Among patients with refractory hyperparathyroidism, prompt parathyroidectomy is suggested.