In the JournalsPerspective

Vitamin D increases fibroblast growth factor 23 in children with advanced CKD

In children with mild to moderate chronic kidney disease, vitamin D supplementation normalized Klotho and sclerostin, according to a study published in Nephrology Dialysis Transplantation. However, the supplements increased fibroblast growth factor 23 in children with advanced CKD.

“Vitamin D deficiency is widely prevalent in children with chronic kidney disease (CKD) and contributes to mineral and bone disorder (MBD),” the authors wrote. “Normal 25-hydroxyvitamin D [25(OJ)D] levels may also reduce proteinuria and attenuate renal failure progression in children with CKD.”

To determine the effects of vitamin D supplementation in children with CKD, researchers selected 80 vitamin D-deficient children for this post-hoc analysis. Investigators studied the effects of vitamin D supplementation on fibroblast growth factor 23 (FGF23), bone alkaline phosphate (BAP), Klotho and sclerostin levels. Half of the patients included were from the randomized trial of ergocalciferol supplementation (ERGO) study and the rest from the Cardiovascular comorbidity in Children with Chronic Kidney Disease (4C) study. In each study, 20 matched children did not receive vitamin D supplementation and served as controls.

Researchers found that in patients with mild to moderate CKD in the ERGO cohort, vitamin D supplementation had no effect on FGF23 or BAP, but normalized Klotho and increased sclerostin levels. Final sclerostin however, did not differ from normal, healthy levels.

In children with advanced CKD in the 4C cohort, vitamin D supplementation increased FGF23 levels, but serum Klotho, BAP and sclerostin remained unaffected.

“This is the first report on the effects of vitamin D supplementation on markers of bone and mineral metabolism beyond PTH in children with CKD,” the authors wrote. “As expected, serum FGF23 was largely in the normal range in the ERGO cohort, but was elevated nine-fold in C4 patients, whose eGFR averaged 24 mL/min/1.73 m2.”

Researchers concluded that the consequences of increased FGF23 levels in patients with advanced CKD receiving vitamin D supplements should be addressed in future interventional trials.

“This observation is at odds with two studies in adult CKD and hemodialysis patients that failed to show a significant increase in circulating Klotho with vitamin D,” the authors wrote. This discrepancy may be at least partly due to an already diminished renal capacity for Klotho synthesis in patients with advanced CKD.” – by Scott Buzby

Disclosures: The authors report no relevant financial disclosures.

 

 

In children with mild to moderate chronic kidney disease, vitamin D supplementation normalized Klotho and sclerostin, according to a study published in Nephrology Dialysis Transplantation. However, the supplements increased fibroblast growth factor 23 in children with advanced CKD.

“Vitamin D deficiency is widely prevalent in children with chronic kidney disease (CKD) and contributes to mineral and bone disorder (MBD),” the authors wrote. “Normal 25-hydroxyvitamin D [25(OJ)D] levels may also reduce proteinuria and attenuate renal failure progression in children with CKD.”

To determine the effects of vitamin D supplementation in children with CKD, researchers selected 80 vitamin D-deficient children for this post-hoc analysis. Investigators studied the effects of vitamin D supplementation on fibroblast growth factor 23 (FGF23), bone alkaline phosphate (BAP), Klotho and sclerostin levels. Half of the patients included were from the randomized trial of ergocalciferol supplementation (ERGO) study and the rest from the Cardiovascular comorbidity in Children with Chronic Kidney Disease (4C) study. In each study, 20 matched children did not receive vitamin D supplementation and served as controls.

Researchers found that in patients with mild to moderate CKD in the ERGO cohort, vitamin D supplementation had no effect on FGF23 or BAP, but normalized Klotho and increased sclerostin levels. Final sclerostin however, did not differ from normal, healthy levels.

In children with advanced CKD in the 4C cohort, vitamin D supplementation increased FGF23 levels, but serum Klotho, BAP and sclerostin remained unaffected.

“This is the first report on the effects of vitamin D supplementation on markers of bone and mineral metabolism beyond PTH in children with CKD,” the authors wrote. “As expected, serum FGF23 was largely in the normal range in the ERGO cohort, but was elevated nine-fold in C4 patients, whose eGFR averaged 24 mL/min/1.73 m2.”

Researchers concluded that the consequences of increased FGF23 levels in patients with advanced CKD receiving vitamin D supplements should be addressed in future interventional trials.

“This observation is at odds with two studies in adult CKD and hemodialysis patients that failed to show a significant increase in circulating Klotho with vitamin D,” the authors wrote. This discrepancy may be at least partly due to an already diminished renal capacity for Klotho synthesis in patients with advanced CKD.” – by Scott Buzby

Disclosures: The authors report no relevant financial disclosures.

 

 

    Perspective

    This is a complex study regarding a complex issue. I think that this study was well designed. However, within pediatrics, we have trouble with getting the numbers; it’s a low number of children involved in [this] study. What was interesting to me was the advanced CKD group (4C cohort) and looking at some of the changes that happened in that group most notably, the increase in FGF23. High levels of FGF23 are associated with left ventricular hypertrophy in patients with CKD. However, again, I think the numbers of patients involved is a factor and there are also other things in the study that were not controlled for that may need to be looked at as well.

    Vitamin D deficiency is prevalent in children with CKD and contributes to their mineral and bone disorder. When looking at the advanced CKD group (4C cohort), it was interesting that the children that were supplemented with vitamin D had less incidents of hypocalcemia, which is one of the things we’re trying to address with vitamin D supplementation.  [It was] also noted that their PTH levels and phosphorus levels were stable vs. the control group of the 4C cohort, which did not get any vitamin D supplementation and appeared to have increases in phosphorus levels, increases in PTH levels and also increases in the incidence of patients with hypocalcemia. It appears that vitamin D supplementation is helping address the issues that we're trying to address, which are related to bone mineralization, however the increase in FGF 23 is concerning as we don’t want to be contributing to an elevation or a further elevation in the FGF23 levels.

    I think, practically thinking, [there’s] probably not enough evidence to stop using vitamin D in advanced CKD, that we probably need more studies, further studies, larger numbers of patients [and] larger groups. But it definitely is something that will make us stop and think about what’s happening. Perhaps, making sure we follow vitamin D levels closer and that when children are sufficiently repleted in their vitamin D levels, that we adjust vitamin D dosing appropriately and not continue to give excessive doses.

    The impact, I think, in clinical practice would be to avoid excessive supplementation and, as needed, improve the vitamin D level, making sure that vitamin D dosing is adjusted appropriately.

    I would say that the study did make me think about the importance of vitamin D supplementation in the earlier stages of CKD to help delay the onset of secondary hyperparathyroidism.

    • Jennifer House, MS, RD, CNSC
    • Georgia Dialysis for Adolescents and Pediatrics
      Tucker, Georgia

    Disclosures: House works for DaVita Kidney Care and reports no relevant financial disclosures.