Of the various options of vitamin D replacement in CKD available, which one is correct for this patient?
A 92-year-old man has CKD stage G4A1 from diabetes. He has a history of skin cancer and has been told to avoid the sun. He lives in Lincoln, Nebraska.
On routine screening, he is noted to have a 25-hydroxyvitamin D level of 16 ng/ml, a calcium level of 8.7 mg/dL, a phosphorus of 3.1 mg/dL, and a PTH, intact of 200 pg/ml.
His nephrologist gives the patient a diagnosis of secondary hyperparathyroidism with Vitamin D deficiency.
Vitamin D replacement in CKD
Levels of vitamin D decline as the CKD stage declines
Vitamin D deficiency is linked to increased iPTH levels in patients with Chronic Kidney Disease (CKD). Supplementation with nutritional vitamin D precursors can help lower iPTH levels towards normal, which is beneficial for bone health.
Both forms of Vitamin D (D2 and D3) can be purchased over the counter, but their biological activity is limited until they undergo hydroxylation in the liver.
The hydroxylation process involves the conversion of vitamin D into calcidiol (25-hydroxyvitamin D or 25(OH)D) in the liver, followed by further hydroxylation by 1α-hydroxylase in the kidneys and other organs to produce 1,25-dihydroxyvitamin D (1,25[OH]2D), the active form known as calcitriol.
Calcitriol, an activated vitamin D analog, is typically reserved for patients with advanced CKD (stages G4 and G5) who are experiencing progressive secondary hyperparathyroidism and is not the immediate next step in management for all patients
The ideal serum concentrations of 25(OH)D can vary based on stage of life, race and ethnicity, and physiological measures used.
Maintaining optimal serum concentrations of 25(OH)D is important for bone and overall health, although definitive ideal levels have not been established.
Discussion:
Vitamin D Replacement in CKD, Chronic Kidney Disease
Screening for Risk Factors
Although the optimal iPTH level is not established, KDIGO guidelines suggest screening for modifiable risk factors, particularly vitamin D deficiency, in patients with elevated iPTH. Here, the patient exhibits elevated iPTH alongside normal calcium and phosphorus levels, but has low 25-hydroxyvitamin D levels. Vitamin D replacement in CKD is recommended.
Vitamin D Deficiency and iPTH Levels
Vitamin D deficiency is linked to increased iPTH levels. Supplementation with nutritional vitamin D precursors can help lower iPTH levels towards normal, which is beneficial for bone health.
Sources of Vitamin D * Vitamin D2: Derived from plant sources and fungi. We chose Vitamin D2 (ergocalciferol) for this patient because he is a vegetarian. * Vitamin D3: Found in fatty fish, egg yolks, and fortified cereals and milk.
Both forms of Vitamin D can be purchased over the counter, but their biological activity is limited until they undergo hydroxylation in the liver.
Hydroxylation Process
The hydroxylation process involves the conversion of vitamin D into calcidiol (25-hydroxyvitamin D or 25(OH)D) in the liver. This is further hydroxylated by 1α-hydroxylase in the kidneys and other organs to produce 1,25-dihydroxyvitamin D (1,25[OH]2D), the active form known as calcitriol.
Use of Activated Vitamin D Analogs
Activated vitamin D analogs, such as calcitriol (1,25-dihydroxyvitamin D), can be ordered by giving the patient a prescription and are typically reserved for patients with advanced CKD (stages G4 and G5) who are experiencing progressive secondary hyperparathyroidism. Therefore, calcitriol is not the immediate next step in management for this patient.
Vitamin D Supplementation Guidelines
Patients with an estimated glomerular filtration rate (eGFR) greater than 30 mL/min and no biochemical evidence of chronic kidney disease-metabolic bone disease (CKD-MBD) should receive vitamin D supplementation similar to those with normal kidney function. However, as kidney failure progresses (eGFR <30 mL/min), those with CKD stages G4 and below, the production of calcitriol may decrease because of the following factors: * Diminished glomerular filtration. * Loss of the 1-alpha-hydroxylase enzyme because of structural kidney damage. * Suppression of enzyme activity from hyperphosphatemia.
This can lead to hypocalcemia, secondary hyperparathyroidism, and bone disease, leading to a review of vitamin D replacement in CKD strategies for this population.
Optimal Serum Concentrations of 25(OH)D
The ideal serum concentrations of 25-hydroxyvitamin D (25(OH)D) for bone and overall health have not been definitively established. These levels may vary based on: * Stage of life. * Race and ethnicity. * Physiological measures used.
While 25(OH)D levels increase with higher vitamin D intake, the relationship is nonlinear, with variations depending on baseline serum levels and the duration of supplementation.
