Assessment and management of magnesium and trace element status in children with CKD stages 2-5, on dialysis and post-transplantation: Clinical practice points from the Pediatric Renal Nutrition Taskforce.

Magnesium (Mg) and trace elements (TEs) are required for essential roles in body processes [1], and body stores can be affected by diet, supplements, kidney function, urine loss, exogenous sources, and dialysis. Deficiency and excess are more common in chronic kidney disease (CKD) and may cause adverse clinical consequences, such as poor growth [2]. Previous pediatric guidelines for mineral and TE management specific to children with CKD are over 15 years old [3, 4] and are based on limited evidence with the absence of attention to some key TEs. The principal messages from these guidelines are that dietary intake should provide 100% of the requirements for healthy children and that supplementation should be considered when there is inadequate intake or clinical evidence of deficiency.

We address the mineral Mg and the TEs chromium (Cr), copper (Cu), fluoride (Fl), iodine (“I”), manganese (Mn), selenium (Se), and zinc (Zn). We present a comprehensive position paper with six clinical practice points (CPPs) to address Mg and TE status, intervention, and monitoring for children with CKD stages 2–5, on dialysis and post-transplantation (CKD2–5D/T). This builds upon the 2009 Kidney Disease Outcomes Quality Initiative recommendations [4] using data from more recent literature and provides new guidance for Mg, Cu, Cr, Fl, “I”, Mn, Se, and Zn in children. These CPPs are based on available evidence, expert opinion and, where appropriate, extrapolation from adult studies. Calcium and phosphate [5], potassium [6], sodium, and iron are out of scope of this CPP and have either been addressed in previous documents or will be discussed in subsequent guidelines.

… Evidence and rationale

We first describe the requirements for healthy children as a comparator to understand the requirements for children with CKD. Table S2 summarizes internationally published recommended dietary intakes of Mg and TEs. Table S3 presents the requirements’ definitions.

The requirements of Mg and TEs for children and young people with CKD have not been determined. Therefore, as an initial guide, the requirements for healthy children should be used, with the exception of advanced CKD (stages 3b to 5D) when Mg and certain TEs, namely “I”, begin to accumulate, and others are lost through dialysis (see “What other factors influence magnesium and trace element status?” for details). The exception is Fl, which accumulates in earlier stages of CKD.

In the early stages of CKD, we recommend increasing intake of Mg and TEs via diet or supplementation, if dietary intake is lower than recommended for healthy children. Children on dialysis may benefit from a higher intake of TEs, but this depends on the quantity of TEs removed by dialysis, which again is dependent on dialysate concentration.

… Fluoride (Fl)

There is a lack of data on Fl status in children in recent years. Fl deficiency is rare in CKD, although there is historical evidence to suggest FI excess in children with CKD [77, 78]. Urinary Fl excretion decreases as GFR declines [77, 79]; according to one study in infants and toddlers receiving PD, blood Fl can be elevated [78], though this is rarely evaluated in practice (expert opinion). There is minimal Fl removal with PD relative to urinary excretion by healthy kidneys [78]. Infants and toddlers receiving PD have higher blood Fl concentrations than healthy controls [78]. There is no data regarding Fl removal by HD. Clinicians should be aware of the Fl content of water (if available from water companies or health authorities) [80, 81], since polyuric infants and children drinking large amounts of fluoridated water (and having their formula reconstituted with fluoridated water) may be at risk of excess Fl intake and elevated blood Fl concentration, especially if they also have a decreased GFR. In all children, Fl excess may occur secondary to Fl supplements, excessive swallowing of Fl-containing toothpaste, and dental Fl treatments; in children with CKD with impaired clearance accumulation could be accelerated [77,78,79].

…Intake of TEs is affected by water and soil contents. For example, location and soil composition of staple crops plays a role in population-level risk assessment of Cr, Se, and Zn status [123,124,125]. Water supplementation is typically the main source of dietary Fl; hence, as shown in a study of adolescents, the Fl concentration of local water largely determines Fl intake [79].

… In children with polyuria and polydipsia, consider risk of fluoride excess with well-fluoridated water.

… Blood Fl is rarely measured in CKD [78]. Measurement of blood Fl may be considered in a child with advanced CKD and a high intake of Fl due to polydipsia with a large intake of fluoridated water or fluoridated products.