A primary care colleague asked this excellent question.
Vitamin D has been found to have role not only in bone and mineral metabolism but also in a wide range of other systems like cardiovascular diseases, diabetes, hypertension and immune system. Vitamin D insufficiency (less than 30ng/ml) and deficiency (less than 15ng/ml) is prevalent in CKD (Chronic Kidney Disease) patients, especially in patients who are african-american, older, with diabetes and hypoalbuminema. A recent study estimated that 79% of ESRD patients on hemodialysis had vitamin D deficiency.
In patients with CKD, there is a progressive loss of renal 1 α hydroxylase activity, which is responsible for the conversion of calcidiol (Vitamin 25OH D) to the active form calcitriol (Vitamin (1,25) OH D3). Lack of calcitriol leads to secondary hyperparathyroidism and subsequent bone and mineral derangements. Hence, active Vitamin D( calcitriol and its analogues) supplementation is routinely done in CKD patients to treat secondary hyperparathyroidism. Several studies have shown that administering active vitamin D leads to significant reduction in mortality in CKD patients and the benefit was much more than treating hyperparathyroidism alone.
There is an ongoing debate regarding the role of concurrent 25(OH)D repletion in CKD patients already treated with calcitriol or its analogues. Since, CKD 3-4 patients have some residual renal 1 α hydroxylase activity, these patients should be screened and treated for Vitamin 25 OH D insufficiency/deficiency to treat secondary hyperparathyroidism.
However, for patients with more advanced CKD (Stage 5) including dialysis patients, it has not been established that vitamin D (ergocalciferol or cholecalciferol) will be effective, since the ability to generate adequate levels of 1,25(OH)2 D3 is markedly reduced. Lately, there has been evidence that 1α hydroxylase enzyme is found in many other sites except the kidneys (such as the parathyroids, pancreas, adrenal medulla, endothelium, smooth vascular cells, skin, and cerebellum), which are intact in CKD patients. This locally produced 1,25(OH)2D is suspected to have “autocrine or paracrine” effects and most likely responsible for the roles for vitamin D, beyond its classical functions in mineral metabolism.
A study reported in the current volume of CJASN shows that vitamin d 25 OH (cholecalciferol) supplementation is safe and cost-effective in dialyisis patients and ‘allows reduction of vitamin D deficiency, better control of mineral metabolism with less use of active vitamin D, attenuation of inflammation, reduced dosing of erythropoiesis-stimulating agents, and possibly improvement of cardiac dysfunction’. However this was a small, short term, nonrandomized study which did not look at outcomes of mortality.Large, long term, prospective studies need to be done in future to prove its beneficial effect and the dose .
Although the evidence is not strong, but since the therapy is relatively safe (side effects being hypercalcemia and hyperphosphatemia), Vitamin 25 OH D levels should be evaluated and correction of 25(OH) D deficiency/insufficiency should probably be done in CKD 5 patients also, similar to the general population as suggested by the Kidney Disease: Improving Global Outcomes (KDIGO) recommendations.
- Vitamin D insufficiency and deficiency is highly prevalent in CKD patients
- Vitamin D 25 OH (either ergocaliciferol or cholecaliferol) should be given to treat vitamin d deficiency/insufficiency in CKD3-4 patients just like the general population.
- Stage 5 CKD patients can also be treated with vitamin D 25 OH for vitamin D deficiency, although the evidence is not strong and long-term studies are not available.
- These CKD patients should be monitored closely for adverse effecs like hypercalcemia and hyperphosphatemia while on vitamin D therapy.