What Kind Of Vitamin D Should CKD Patients Take?

As we all know, the common complication of chronic kidney disease (CKD) is chronic kidney disease mineral and bone abnormalities (CKD-MBD), which is one of the important causes of disability, death and other adverse outcomes of CKD patients. Studies have confirmed that vitamin D can effectively reduce the level of parathyroid hormone (PTH) and reduce the risk of vascular calcification progression in patients with CKD with vitamin D deficiency, thereby delaying the progression of CKD-MBD and improving the final prognosis. However, vitamin D is a large family that includes a series of members such as natural vitamin D, calcidiol, and calcitriol. Are these members all equally effective in CKD/CKD-MBD patients with vitamin D deficiency?

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On November 11, 2022, a research team from the United States published a study in BMC Nephrology. This study showed that calcifediol extended-release (ERG) was effective in increasing 25-hydroxyvitamin D levels and reducing PTH levels compared with active vitamin D and its analogs (AVD) and natural dietary vitamin D (NVD), and Does not increase blood calcium.

Methods

This is a real-world study using data from a clinical database of nephrology clinics in 15 different regions of the United States. The enrolled patients meet the following four conditions: ①adult patients with CKD stage 3-4, that is, the estimated glomerular filtration rate (eGFR) is between 15-60ml/min/1.73㎡; ②patients have secondary parathyroid function Hyperactivity (SHPT) and vitamin D deficiency; ③Patients have a history of ERC, NVD or AVD treatment, and have medical records for ≥6 months before and after enrollment; ④Do not receive renal replacement therapy. A total of 1917 patients were screened, and finally, a total of 376 patients were included. Patients were divided into ERC (n = 174), AVD (n = 55), and NVD (n = 147) groups according to the type of vitamin D they were taking.

The primary endpoints of the study were changes in 25-hydroxyvitamin D and PTH levels. Secondary endpoints were changes in serum calcium and phosphorus levels.

Results

The baseline age of all patients was 69.5 (SD: 13.2) years old, 185 cases (49.2%) were male, body mass index (BMI) was 32.8 (SD: 15.2) kg/㎡, most (55.6%) of the patients had CKD etiology Hypertension, followed by diabetes (38.9%). 204 (54.3%) patients had CKD stage 3, and 172 (45.7%) patients had CKD stage 4. The baseline characteristics of patients in each group and the dosage information of vitamin D and its analogs are shown in the table below (Table 1).

In terms of the primary endpoint, the baseline 25-hydroxyvitamin D and PTH levels of patients in the ERC group were 20.3±0.7ng/ml and 181.4±7.4pg/ml, respectively. After 23.4-28.8 weeks of follow-up, the 25-hydroxyvitamin D level rose to 23.7±1.6ng /ml (P ＜ 0.001), while PTH decreased by 34.1±6.6pg/ml (18.8%, P ＜ 0.001). At the same time, no significant changes were found in the blood calcium and phosphorus levels of the patients.

The baseline levels of 25-hydroxyvitamin D and PTH in the AVD group were 23.5±1.0ng/ml and 156.9±9.7pg/ml, respectively. After 21.3-24.5 weeks of follow-up, only 5.5±1.3ng/ml of 25-hydroxyvitamin D was found. However, PTH levels and serum phosphorus levels did not change significantly. Notably, blood calcium levels were significantly elevated by 0.2 ± 0.1 mg/dl (p < 0.001).

The baseline levels of 25-hydroxyvitamin D and PTH in the NVD group were 18.6±0.6ng/ml and 134.8±6.8pg/ml, respectively. After 18.3-21.1 weeks of follow-up, only 25-hydroxyvitamin D was found to increase by 9.7±1.5ng/ml ( p<0.001). However, PTH, blood calcium, and blood phosphorus levels had no significant changes.

Regardless of the percentage of patients with 25-hydroxyvitamin D > 30 ng/ml after follow-up, the percentage of patients with a decrease in PTH > 30%, and the percentage of patients with 25-hydroxyvitamin D > 30 ng/ml at the end of follow-up but < 20 ng/ml at baseline, the ERC group have significant advantages.

Discussion

In a real-world clinical setting, ERC was found to be the only treatment that significantly reduced mean PTH in non-dialysis CKD patients. The fact that AVD did not reduce PTH levels was somewhat unexpected and may have been related to under-prescribing. It is expected that NVD does not reduce PTH levels, and the reason is mainly related to the following two points: first, many Meta-analyses show that NVD cannot reduce PTH, and second, it is difficult for NVD to improve 25-hydroxyvitamin D in overweight/obese patients Level. In the United States, most CKD patients are overweight, and some patients in this study were overweight/obese.

It is worth noting that the average increase level of 25-hydroxyvitamin D in the ERC group (23.7 ng/ml) was the largest, which was significantly better than that in the AVD (5.5 ng/ml) and NVD groups (21.1 ng/ml). At the same time, in this study, if the dose of ERC is increased, not only will there be no safety issues, but the efficacy will also be improved. Although increasing the dose of AVD can also improve efficacy, patients in the AVD group had a significantly small increase in serum calcium levels, which may increase the risk of CKD-MBD progression.

The current research results show that for SHPT and vitamin D-deficient stage 3-4 CKD patients, ERC can significantly increase the level of 25-hydroxyvitamin D, reduce the level of PTH, and have no significant effect on the homeostasis of blood calcium and blood phosphorus.

for more information: Ali.ma@wecistanche.com