Effects of ferric citrate and intravenous iron sucrose on markers of mineral, bone, and iron homeostasis in a rat model of CKD-MBD

AUTHORS

Annabel Biruete, Corinne E Metzger, Neal X Chen, Elizabeth A Swallow, Curtis Vrabec, Erica L Clinkenbeard, Alexander J Stacy, Shruthi Srinivasan, Kalisha O'Neill, Keith G Avin, Matthew R Allen, Sharon M Moe

ABSTRACT

Background

Anemia and chronic kidney disease-mineral and bone disorder (CKD-MBD) are common and begin early in CKD. Limited studies have concurrently compared the effects of ferric citrate (FC) vs. IV iron on CKD-MBD and iron homeostasis in moderate CKD.

Methods

We tested the effects of 10 weeks of 2% FC vs. IV iron sucrose in rats with moderate CKD (Cy/+ male rat) and untreated normal (NL) littermates. Outcomes included a comprehensive assessment of CKD-MBD, iron homeostasis, and oxidative stress.

Results

CKD rats had azotemia, elevated phosphorus, PTH, and FGF23. Compared to untreated CKD rats, treatment with FC led to lower plasma phosphorus, intact FGF23, and a trend (p = 0.07) towards lower C-terminal FGF23. FC and IV iron equally reduced aorta and heart calcifications to levels similar to NL animals. Compared to NL animals, CKD animals had higher bone turnover, lower trabecular volume, and no difference in mineralization; these were unaffected by either iron treatment. Rats treated with IV iron had cortical and bone mechanical properties similar to NL animals. FC increased transferrin saturation rate compared to untreated CKD and NL rats. Neither iron treatment increased oxidative stress above that of untreated CKD.

Conclusions

Oral FC improved phosphorus homeostasis, some iron-related parameters, and the production and cleavage of FGF23. The intermittent effect of low-dose IV iron sucrose on cardiovascular calcification and bone should be further explored in moderate-to advanced CKD.

Clinical Prediction of High-Turnover Bone Disease After Kidney Transplantation

AUTHORS

Satu M. Keronen, Leena A. L. Martola, Patrik Finne, Inari S. Burton, Xiaoyu F. Tong, Heikki P. Kröger & Eero O. Honkanen

ABSTRACT

Bone histomorphometric analysis is the most accurate method for the evaluation of bone turnover, but non-invasive tools are also required. We studied whether bone biomarkers can predict high bone turnover determined by bone histomorphometry after kidney transplantation. We retrospectively evaluated the results of bone biopsy specimens obtained from kidney transplant recipients due to the clinical suspicion of high bone turnover between 2000 and 2015. Bone biomarkers were acquired concurrently. Of 813 kidney transplant recipients, 154 (19%) biopsies were taken at a median of 28 (interquartile range, 18–70) months after engraftment. Of 114 patients included in the statistical analysis, 80 (70%) presented with high bone turnover. Normal or low bone turnover was detected in 34 patients (30%). For discriminating high bone turnover from non-high, alkaline phosphatase, parathyroid hormone, and ionized calcium had the areas under the receiver operating characteristic curve (AUCs) of 0.704, 0.661, and 0.619, respectively. The combination of these markers performed better with an AUC of 0.775. The positive predictive value for high turnover at a predicted probability cutoff of 90% was 95% while the negative predictive value was 35%. This study concurs with previous observations that hyperparathyroidism with or without hypercalcemia does not necessarily imply high bone turnover in kidney transplant recipients. The prediction of high bone turnover can be improved by considering alkaline phosphatase levels, as presented in the logistic regression model. If bone biopsy is not readily available, this model may serve as clinically available tool in recognizing high turnover after engraftment.