Clinical Practice Guidelines for Bone Metabolism and Disease in Chronic Kidney Disease: An Overview

George R. Bailie, PharmD, PhD, FCCP; Shaul G. Massry, MD

Disclosures

Pharmacotherapy. 2005;25(12):1687-1707. 

In This Article

Guideline 7: Prevention and Treatment of Vitamin D Insufficiency and Vitamin D Deficiency in Patients with Chronic Kidney Disease

Guideline Statements

In Stages 3 and 4

7.1 - If plasma iPTH is above the target range for the stage of CKD ( Table 3 ), serum 25-hydroxyvitamin D (25[OH]D) concentration should be measured at first encounter. If it is within normal limits, repeat annually (E).

7.2 - If the serum concentration of 25(OH)D is below 30 ng/ml (75 nmol/L), supplementation with vitamin D2 (ergocalciferol) should be started (O).

7.3 - After starting vitamin D therapy:

 

7.3a - The use of ergocalciferol therapy should be integrated with the serum calcium and phosphorus concentrations (Figure 2).

 

 

7.3b - Serum concentrations of corrected total calcium and phosphorus should be measured at least every 3 months (O).

 

 

7.3c - If the serum concentration of corrected total calcium exceeds 10.2 mg/dl (2.54 mmol/L), discontinue ergocalciferol therapy and all forms of vitamin D therapy (O).

 

 

7.3d - If the serum phosphorus concentration exceeds 4.6 mg/dl (1.49 mmol/L), add or increase the dosage of phosphorus binder. If hyperphosphatemia persists, discontinue vitamin D therapy (O).

 

 

7.3e - Once patients are replete with vitamin D, continue supplementation with a vitamin D-containing multivitamin preparation, with annual reassessment of serum 25(OH)D concentrations and the continued assessment of corrected total calcium and phosphorus concentrations every 3 months (O).

 

Figure 2.

Vitamin D supplementation in stages 3 and 4 CKD. 25(OH)D = 25-hydroxyvitamin D. Guidelines 4, 5, and 8A are specific guidelines in the Kidney Disease Outcomes Quality Initiative (K/DOQI). aVitamin D2 (ergocalciferol) may be safer than vitamin D3 (cholecalciferol). When the 25(OH)D concentration is below 15 ng/ml (37 nmol/L), a dosage of 50,000 IU weekly for four doses followed by 50,000 IU monthly for four doses is effective. With 25(OH)D concentrations of 20-30 ng/ml (50-75 nmol/L), 50,000 IU monthly for six doses is recommended. (Adapted with permission from reference 3, algorithm 1.)

In Stage 5

7.4 - Therapy with an active vitamin D sterol (calcitriol, alfacalcidol, paricalcitol, or doxercalciferol) should be provided if the plasma concentration of iPTH is above 300 pg/ml (300 ng/L) (O).

This guideline again recommends separate interventions for patients at different stages of CKD. In stages 3 and 4, it is intended to provide oral vitamin D if patients are proved vitamin D insufficient or deficient, and in stage 5 CKD vitamin D therapy is prompted by elevated plasma PTH concentrations.

Serum concentrations of 25(OH)D—not 1,25-dihydroxyvitamin D—are the measure of body stores of vitamin D. In healthy individuals older than 60 years, 25(OH)D concentrations below the normal limit of 15 ng/ml and also low-to-normal concentrations of 16-32 ng/ml are both associated with increased PTH concentrations, reduced bone mineral density, and increased rates of hip fracture. Such concentrations of 25(OH)D are not infrequent in patients with stages 3-5 CKD. Thus, the prevention and treatment of vitamin D insufficiency in patients with stages 3 and 4 CKD probably reduce the frequency and severity of secondary hyperparathyroidism. In patients with stage 5 CKD, administration of active vitamin D sterols is necessary when plasma concentrations of PTH exceed 300 pg/ml.

Patients with CKD or those who are dialysis dependent are much more likely to have low concentrations of 25(OH)D compared with those with no kidney disease, for several reasons. First, many are inactive with reduced exposure to sunlight. Second, the ingestion of foods that are natural sources of vitamin D (fish, cream, milk, and butter) tends to be lower than in the population with normal kidneys. Third, serum 25(OH)D concentrations may be subnormal in patients with CKD because the endogenous synthesis of vitamin D3 in the skin after identical exposure to sunlight is reduced in those with reduced GFR, in individuals older than 60 years, and in individuals with increased melanin content of the skin.

In patients with GFRs of 20-60 ml/minute/1.73 m,2 both nutritional vitamin D deficiency and insufficiency can be prevented by supplementation with vitamin D2 (ergocalciferol) or vitamin D3 (cholecalciferol). If there is evidence of true vitamin D deficiency, this should be treated by using vitamin D2, although the dosages needed are larger than those needed for vitamin D insufficiency. For the prevention of vitamin D deficiency, the recommended daily allowance for vitamin D in individuals older than 60 years is 800 IU, and for younger adults 400 IU.

In the United States, the only dosage forms available are 400 IU (over the counter) and capsules containing 50,000 IU (requiring a prescription). In healthy individuals, the recommended upper limit of vitamin D is 2000 IU/day of ergocalciferol, which can be achieved by giving one capsule (50,000 IU) once/month. Calcitriol or another 1α-hydroxylated vitamin D sterol should not be used to treat vitamin D deficiency. When evidence of severe vitamin D deficiency is found (25[OH]D concentrations < 5 ng/ml [12 nmol/L]), rickets or osteomalacia may be present. Under these circumstances, patients can be treated by using ergocalciferol 50,000 IU/week for 12 weeks and monthly thereafter ( Table 6 ). The balance between dosing vitamin D supplementation and changes in serum calcium and phosphorus concentrations may be difficult, and pharmacists are counseled to review the algorithm in Figure 2. Although many community pharmacists will not have access to the relevant laboratory values, pharmacists in institutional settings may be well positioned to help adjust therapy as appropriate. Again, this could be particularly important should the patient not be under the care of a nephrologist.

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