Carbonyl iron and iron dextran therapies cause adverse effects on bone health in juveniles with chronic kidney disease

Abstract

The Nijmegen Biomedical Study is a population-based cross-sectional study conducted in the eastern part of the Netherlands. As part of the overall study, we provide reference values of estimated glomerular filtration rate (GFR) for this Caucasian population without expressed risk. Age-stratified, randomly selected inhabitants received a postal questionnaire on lifestyle and medical history. In a large subset of the responders, serum creatinine was measured. The GFR was then measured using the abbreviated Modification of Diet in Renal Disease (MDRD) formula. To limit possible bias, serum creatinine was calibrated against measurements performed in the original MDRD laboratory. The study cohort included 2823 male and 3274 female Caucasian persons aged 18-90 years. A reference population of apparently healthy subjects was selected by excluding persons with known hypertension, diabetes, cardiovascular-or renal diseases. This healthy study cohort included 1660 male subjects and 2072 female subjects, of which 869 of both genders were 65 years or older. The median GFR was 85 ml/min/1.73 m 2 in 30-to 34-year-old men and 83 ml/min/1.73 m 2 in similar aged women. In these healthy persons, GFR declined approximately 0.4 ml/min/year. Our study provides age-and gender-specific reference values of GFR in a population of Caucasian persons without identifiable risk.

The HIF-PHI BAY 85-3934 (Molidustat) Improves Anemia and Is Associated With Reduced Levels of Circulating FGF23 in a CKD Mouse Model

“…However, iron suppressed bone formation markers, reduced trabecular parameters, and caused cortical thinning. ( 63 ) Bone properties are not currently being examined as primary endpoints in ongoing HIF‐PHI clinical trials but may be an important outcome to examine in the future as these drugs become fully available. Several in vitro studies have shown that stabilized HIF, through genetic or chemical treatment, induced FGF23 expression.…”

Iron therapy mitigates chronic kidney disease progression by regulating intracellular iron status of kidney macrophages

“…We used a high-adenine diet mouse model of CKD ( 8 ) ( Figure 1A ). CKD mice developed severe kidney fibrosis ( Figure 1B ) and displayed systemic hypoferremia with low serum iron, low transferrin saturation, and high serum soluble transferrin receptor levels, ( Supplemental Figure 1 ; supplemental material available online with this article; https://doi.org/10.1172/jci.insight.159235DS1 ).…”

“…Recently, we reported that chronic parenteral administration of iron dextran improves kidney function in juvenile mice with adenine-induced CKD ( 8 ). Similarly, ferric citrate coordination complex improved kidney function in 5/6-nephrectomized rats ( 9 ) and in juvenile mice with Alport syndrome ( 10 ).…”

“…Although iron therapy is being widely used in patients with CKD, the effects of iron on kidney macrophage behavior in the context of CKD remain largely unexplored ( 6 ). Owing to elevated hepcidin, macrophages may accumulate iron intracellularly in CKD ( 8 ). In macrophages, iron can join the labile iron pool (LIP), a cytosolic pool of free redox-active ferrous iron (Fe 2+ ) ( 21 ).…”

Renoprotective effects of ferric citrate in a mouse model of chronic kidney disease

“…In pre-clinical CKD models, differential effects of iron therapy on kidney function and fibrosis have been observed, depending on the specific iron preparation and the route of administration 70 . For instance, in one study of mice with adenine diet-induced CKD, oral carbonyl iron worsened kidney function, but intraperitoneal iron dextran improved kidney function, a difference possibly contributed to by the systemic pro-inflammatory effect of chronic oral carbonyl iron administration 71 .…”