CKD - Calcium and phosphate metabolism

Question 1

The principal complications of abnormalities of calcium and phosphate metabolism in CKD occur in the ____

Answer 1

Skeleton and the vascular bed, with occasional severe involvement of soft tissues

Question 2

The major disorders of bone disease can be classified into:

Answer 2

• Those associated with high bone turnover with increased PTH levels (including osteitis fibrosa cystica, the classic lesion of secondary hyperparathyroidism)
• Osteomalacia due to reduced action of the active forms of vitamin D
• Low bone turnover with low or normal PTH levels (adynamic bone disease)
• Combinations of the foregoing (most often)

Question 3

The pathophysiology of secondary hyperparathyroidism and the consequent high-turnover bone disease is related to abnormal mineral metabolism through the following events:

Answer 3

1. Declining GFR leads to reduced excretion of phosphate and, thus, phosphate retention
2. Retained phosphate stimulates increased synthesis of both FGF-23 by osteocytes and PTH and stimulates growth of parathyroid gland mass;
3. Decreased levels of ionized calcium, resulting from suppression of calcitriol production by FGF-23 and by the failing kidney, as well as phosphate retention, also stimulate PTH production.

Question 4

Calcitriol

• Level in CKD patients
• Effect

Answer 4

• Level in CKD patients
  
  • Low
• Effect
  
  • Contribute to hyperparathyroidism, both by leading to hypocalcemia and also by a direct effect on PTH gene transcription

Question 5

Bone manifestations in CKD start to appear when?

Answer 5

When the GFR falls below 60 mL/min

Question 6

FGF-23

• Source
• Level in CKD
• Relationship with phosphorus
• Relationship with CKD

Answer 6

• Source
  
  • Osteocytes
• Level in CKD
  
  • Increase early in the course of CKD, even before phosphate retention and hyperphosphatemia
• Relationship with phosphorus
  
  • May defend normal serum phosphorus in at least three ways:
    
    1. increased renal phosphate excretion
    2. stimulation of PTH, which also increases
       renal phosphate excretion; and
    3. suppression of the formation of
       1,25(OH)₂D₃, leading to diminished phosphorus absorption from the GI tract
• Relationship with CKD
  
  • Interestingly, high levels of FGF-23 are also an independent risk factor for left ventricular hypertrophy and mortality in CKD, dialysis, and kidney transplant patients
  • Elevated levels of FGF-23 may indicate the need for therapeutic intervention (e.g., phosphate restriction), even when serum phosphate levels are within the normal range

Question 7

Hyperparathyroidism

• Sequela
• Bone histology of sequela
• Clinical manifestations of severe hyperPTH

Answer 7

• Sequela
  
  • Osteitis fibrosa cystica
• Bone histology of sequela
  
  • Abnormal osteoid, bone and bone marrow fibrosis, and in advanced stages, the formation of bone cysts, sometimes with hemorrhagic elements so that they appear brown in color, hence the term brown tumor
• Clinical manifestations of severe hyperPTH
  
  • Bone pain and fragility
  • Brown tumors
  • Compression syndromes
  • Erythropoietin (EPO) resistance in part related to the bone marrow fibrosis

Question 8

T/F. PTH itself is considered a uremic toxin

Answer 8

• True
• High levels are associated with muscle weakness, fibrosis of cardiac muscle, and nonspecific constitutional symptoms

Question 9

Adynamic bone disease

• Increasing prevalence in these population
• Characterized by
• Result from

Answer 9

• Increasing prevalence in these population
  
  • Diabetics and the elderly
• Characterized by
  
  • Reduced bone volume and mineralization
• Result from
  
  • Excessive suppression of PTH production, chronic inflammation, or both

Question 10

Adynamic bone disease is characterized by reduced bone volume and mineralization and may result from excessive suppression of PTH production, chronic inflammation, or both. Suppression of PTH can result from:

Answer 10

• Use of vitamin D preparations; or
• Excessive calcium exposure in the form of calcium-containing phosphate binders or highcalcium dialysis solutions

Question 11

Complications of adynamic bone disease include an increased incidence of fracture and bone pain and an association with increased vascular and cardiac calcification. Occasionally the calcium will precipitate in the soft tissues into large concretions termed ____

Answer 11

“Tumoral calcinosis”

Question 12

Patients with adynamic bone disease often experience the most severe symptoms of musculoskeletal pain. Why?

Answer 12

Owing to the inability to repair the microfractures that occur properly as a part of healthy skeletal homeostasis with regular physical activity

Question 13

Recent epidemiologic evidence has shown a strong association between hyperphosphatemia and ____

Answer 13

Increased cardiovascular mortality in patients with stage 5 and earlier stages of CKD

• Note:*
• Studies using computed tomography (CT) and electron-beam CT scanning show that CKD patients have calcification of the media in coronary arteries and even heart valves that appear to be orders of magnitude greater than that in patients without renal disease

Question 14

Calciphylaxis is a devastating condition seen almost exclusively in patients with advanced CKD. It is heralded by:

Answer 14

Livedo reticularis and advances to patches of ischemic necrosis, especially on the legs, thighs, abdomen, and breasts

Question 15

Pathologically, in calciphylaxis, there is evidence of:

Answer 15

Vascular occlusion in association with extensive vascular and soft tissue calcification

Question 16

It appears that calciphylaxis is increasing in incidence. Originally it was ascribed to ____. However, more recently, calciphylaxis has been seen with increasing frequency in the absence of ____

Answer 16

• Severe abnormalities in calcium and phosphorus control in dialysis patients, usually associated with advanced hyperparathyroidism
• Severe hyperparathyroidism

Question 17

____ treatment is considered a risk factor for calciphylaxis, and if a patient develops this syndrome, this medication should be discontinued.

Answer 17

Warfarin

Question 18

The optimal management of secondary hyperparathyroidism and osteitis fibrosa is ____

Answer 18

Prevention

Question 19

Careful attention should be paid to the plasma phosphate concentration in CKD patients, who should be counseled on a low-phosphate diet as well as the appropriate use of phosphate-binding agents. These are agents that are taken ____ meals so that ____

Answer 19

• With
• There is limitation in its GI absorption

Question 20

Phosphate binders

• Examples
• Major side effect of calcium-based phosphate binders
• Solution to above

Answer 20

• Examples
  
  • Calcium acetate and calcium carbonate
• Major side effect
  
  • Calcium accumulation and hypercalcemia, especially in patients with low-turnover bone disease
• Solution to above
  
  • Sevelamer and lanthanum are non-calcium-containing polymers that also function as phosphate binders
  • They do not predispose CKD patients to hypercalcemia
  • May attenuate calcium deposition in the vascular bed

Question 21

____ exerts a direct suppressive effect on PTH secretion and also indirectly suppresses PTH secretion by raising the concentration of ionized calcium

Answer 21

Calcitriol

Question 22

Major side effect of calcitriol

Answer 22

Calcitriol therapy may result in hypercalcemia and/or hyperphosphatemia through increased GI absorption of these minerals