Mineral and Bone Disorder Monitoring and Therapy

Deranged mineral and bone metabolism as well as the therapy used to correct these abnormalities can lead to skeletal as well as extraskeletal, especially cardiovascular, complications. There is a strong association between CKD-MBD Chronic kidney disease mineral bone disease, CVD, and mortality. The latter two have received increased attention recently. It is, therefore, important to identify and correct these abnormalities in dialysis patients. The following recommendations are based on the KDIGO Kidney Diseases improving global outcomes CKD-MBD guidelines:

1. We recommend that serum levels of calcium, phosphorus, parathyroid hormone (PTH), and alkaline phosphatase should be monitored regularly.

2. We suggest basing the frequency of monitoring on the presence and magnitude of abnormalities. For stable levels, the monitoring should be at longer intervals and for unstable levels or after any change in treatment, more frequent monitoring intervals are recommended to monitor for trends and treatment efficacy and side effects.

3. We suggest that the following frequencies may be used:

   1. Serum calcium and phosphorus 1–3 months
   2. Alkaline phosphatase 3–6 months
   3. PTH 6–12 months

4. We suggest monitoring of 25(OH)vitamin D at baseline and then repeated testing determined by baseline values and therapeutic interventions. However, when finances are a concern, administration of cholecalciferol in a dose of 60,000 units once every 2–4 weeks without measuring levels is reasonable

5. We recommend therapeutic decisions on the basis of trends rather than on a single laboratory value and the entire clinical picture should be taken into consideration rather than just the one parameter

6. We suggest that services of a laboratory that the nephrologist is familiar with should be used both for following a patient longitudinally and for comparing readings between patients

7. We suggest that in case of inconsistent or variable results that are not consistent with the clinical picture, the laboratory should be contacted and the test should be repeated before making a therapeutic decision

8. In patients with evidence of CKD-MBD and/or risk of osteoporosis, we suggest bone mineral density testing to assess fracture risk if results will impact treatment decisions

9. We recommend an abdominal X-ray (lateral view) at baseline

10. We suggest that echocardiogram should be done to detect the presence or absence of valvular calcification

11. We recommend the following goals of treatment of CKDMBD:

    • a)
      If the serum phosphorus levels are elevated, the goal should be to reduce them toward the reference range using phosphate-binding agents.
    • b)
      Hypercalcemia should be avoided.
    • c)
      The intact PTH (iPTH) levels should be maintained in the range of approximately 2–9 times of the upper normal limit for the assay.

12. We recommend 25(OH)vitamin D replacement in everyone with levels in insufficient or deficient range

13. We suggest that children and adolescents who continue to experience height deficits despite correction of malnutrition and biochemical abnormalities of CKD- MBD should be treated with recombinant human growth hormone when additional growth is desired.

Nephrologists should be aware of the methodologies used by the laboratories and request the laboratories to inform them of any change in assay method. The person in-charge of drawing samples should be familiar with the requirement of sample source (whole blood, plasma, or serum), drawing requirements (e.g., vacutainers and needle size), and sample handling specifications (such as storage and transport conditions and temperature) to prevent inappropriate interpretation.

Treatment of Hyperphosphatemia

1. We recommend that all patients with persistent or progressively rising hyperphosphatemia (values above the reference range) should be started on dietary phosphate binders. Patients should be expressly instructed to take phosphate binders with meals.

2. We suggest that in patients receiving phosphate binders, the dose of calcium-based phosphate binders needs to be restricted

3. We recommend that the dialysate calcium concentration should be kept between 5 and 6 mg/dL to allow the optimal use of calcium-containing phosphate binders.

4. We suggest that limiting dietary phosphate intake for treatment of hyperphosphatemia should be considered in patients who do not show evidence of malnutrition

5. We suggest that dialysis duration and/or frequency should be increased, if the serum phosphate levels do not come down with maximal doses of phosphate binders

6. We suggest that high-flux HD, (HF) hemofiltration, or daily dialysis can be offered as per availability and resources in the context of overall patient management

Treatment of Hyperparathyroidism

1. We recommend that in patients with persistently high serum PTH levels, treatment with calcimimetics, calcitriol, or Vitamin D analogs, or a combination of calcimimetics with calcitriol or Vitamin D analogs, should be initiated

2. We recommend that the iPTH levels should be maintained in the range of approximately 2–9 times of the upper normal limit for the assay

3. We suggest that treatment should be initiated or modified if the levels show a consistent increase or decrease in one direction, even when they are within this range. This is suggested to avoid progression to levels outside of this range

4. We recommend that patients who continue to exhibit high iPTH levels despite adequate Vitamin D and/or calcimimetics should be worked up to evaluate for the development of parathyroid adenoma using ultrasound and/or CT scan and myocardial perfusion scan..

5. We recommend that patient who continues to exhibit high iPTH levels and is found to have a solitary adenoma should be treated with alcohol injection by an experienced operator and/or surgical removal.

6. We suggest that children who show persistent growth failure despite correction of malnutrition and biochemical abnormalities of CKD-MBD should be treated with recombinant human growth hormone when additional growth is desired.

Caution

1. We recommend that Vitamin D analog use should be avoided in patients with hypercalcemia and/or if serum PTH levels are persistently low.

2. We recommend that Vitamin D analogs should be reduced or stopped in patients with persistent hyperphosphatemia.

3. We recommend that Vitamin D analogs, and/or calcimimetics, should be reduced or stopped if iPTH levels decrease to less than two times the upper limit of normal.

4. We recommend that calcimimetics be reduced or stopped in patients with hypocalcemia, especially if it is severe and/or clinical signs and symptoms appear.