Non-renal-Related Mechanisms of FGF23 Pathophysiology

Purpose of reviewWe will review non-renal-related mechanisms of fibroblast growth factor 23 (FGF23) pathophysiology.Recent findingsFGF23 production and metabolism may be affected by many bone, mineral, and kidney factors. However, it has recently been demonstrated that other factors, such as iron status, erythropoietin, and inflammation, also affect FGF23 production and metabolism. As these non-mineral factors are especially relevant in the setting of chronic kidney disease (CKD), they may represent emerging determinants of CKD-associated elevated FGF23 levels. Moreover, FGF23 itself may promote anemia and inflammation, thus contributing to the multifactorial etiologies of these CKD-associated comorbidities. CKD-relevant, non-mineral-related, bidirectional relationships exist between FGF23 and anemia, and between FGF23 and inflammation. Iron deficiency, anemia, and inflammation affect FGF23 production and metabolism, and FGF23 itself may contribute to anemia and inflammation, highlighting complex interactions that may affect aspects of CKD pathogenesis and treatment

Treatment of Pediatric Chronic Kidney Disease-Mineral and Bone Disorder

Purpose of reviewIn this paper, we review the pathogenesis and treatment of chronic kidney disease-mineral and bone disorder (CKD-MBD), especially as it relates to pediatric CKD patients.Recent findingsDisordered regulation of bone and mineral metabolism in CKD may result in fractures, skeletal deformities, and poor growth, which is especially relevant for pediatric CKD patients. Moreover, CKD-MBD may result in extra-skeletal calcification and cardiovascular morbidity. Early increases in fibroblast growth factor 23 (FGF23) levels play a key, primary role in CKD-MBD pathogenesis. Therapeutic approaches in pediatric CKD-MBD aim to minimize complications to the growing skeleton and prevent extra-skeletal calcifications, mainly by addressing hyperphosphatemia and secondary hyperparathyroidism. Ongoing clinical trials are focused on assessing the benefit of FGF23 reduction in CKD. CKD-MBD is a systemic disorder that has significant clinical implications. Treatment of CKD-MBD in children requires special consideration in order to maximize growth, optimize skeletal health, and prevent cardiovascular disease

Fractures and Osteomalacia in a Patient Treated With Frequent Home Hemodialysis

Bone deformities and fractures are common consequences of renal osteodystrophy in the dialysis population. Persistent hypophosphatemia may be observed with more frequent home hemodialysis regimens, but the specific effects on the skeleton are unknown. We present a patient with end-stage renal disease treated with frequent home hemodialysis who developed severe bone pain and multiple fractures, including a hip fracture and a tibia-fibula fracture complicated by nonunion, rendering her nonambulatory and wheelchair bound for more than a year. A bone biopsy revealed severe osteomalacia, likely secondary to chronic hypophosphatemia and hypocalcemia. Treatment changes included the addition of phosphate to the dialysate, a higher dialysate calcium concentration, and increased calcitriol dose. Several months later, the patient no longer required a wheelchair and was able to ambulate without pain. Repeat bone biopsy revealed marked improvements in bone mineralization and turnover parameters. Also, with increased dialysate phosphate and calcium concentrations, as well as increased calcitriol, circulating fibroblast growth factor 23 levels increased

Clinical experience with the use of ferric citrate as a phosphate binder in pediatric dialysis patients

BackgroundFerric citrate, an iron-based phosphate binder, has been shown to improve both hyperphosphatemia and iron deficiency in adult chronic kidney disease patients, but its use in the pediatric dialysis population has not been described.MethodsThis is a retrospective analysis of 11 unselected pediatric dialysis patients who received ferric citrate as a phosphate binder between 2015 and 2017. Time-averaged laboratory values were compared pre- and post-ferric citrate initiation using the Wilcoxon signed-rank test.ResultsThe median age of this cohort was 13 years old (range 4-17 years old). Five patients were on hemodialysis, and six patients were on peritoneal dialysis. The median duration of ferric citrate therapy was 214 days (range 39-654 days), with a median time-averaged ferric citrate dose of 3.5 tablets per day (range 1.5-8.4 tablets per day). Compared to the pre-ferric citrate period, ferric citrate treatment was associated with decreased serum phosphate (6.5 to 5.2 mg/dl, p = 0.014), decreased phosphate age-related standard deviation score (SDS) (2.3 to 0.9, p = 0.019), increased transferrin saturation (26 to 34%, p = 0.049), increased ferritin (107 to 230 ng/ml, p = 0.074), and maintenance of hematocrit.ConclusionsIn pediatric dialysis patients, ferric citrate may be able to concurrently lower phosphate levels and treat iron deficiency. However, larger studies are needed to further evaluate safety and efficacy in the pediatric chronic kidney disease population