Mineral (Mal)Adaptation to Kidney Disease—Young Investigator Award Address

Abstract

In the short time since its initial discovery as the cause of rare hypophosphatemic disorders, fibroblast growth factor-23 (FGF-23) has emerged as a major regulator of mineral metabolism and critical component of the bone and mineral adaptation to CKD. However, because elevated FGF-23 levels are also a novel biomarker and possible molecular mediator of increased risks of cardiovascular disease and death in CKD, the initially adaptive response to increase FGF-23 levels to maintain neutral phosphate balance in CKD may ultimately become maladaptive. Incorporating FGF-23 into understanding the complex physiology that governs normal bone and mineral metabolism and its alterations in CKD has filled critical knowledge gaps and opened a new landscape of exciting hypotheses and novel therapeutic strategies to be tested in the continued quest to alleviate the burden of CKD.

Active Vitamin D in Chronic Kidney Disease: Getting Right Back Where We Started from?

“…Thirteen percent of patients with an estimated glomerular filtration rate (eGFR) > 80 mL/min have calcitriol levels < 22 pg/mL, and 13% patients with an eGFR > 80 mL/min have PTH levels > 65 pg/dL [1]. Further, studies in CKD patients suggested that serum levels of fibroblast growth factor 23 (FGF23), a phosphaturic hormone, increases before PTH in the course of renal function decline [2]. Serum calcium and phosphorus remain normal until eGFR declines below 40 mL/min [1].…”

Moderate chronic kidney disease impairs bone quality in C57Bl/6J mice

“…Bone quality is the comprehensive state of tissue microarchitecture and bone material properties including mechanical response, mineralization, collagen cross-linking, and accumulation of microdamage [Donnelly 2011, Seeman & Delmas, 2006]. CKD is a disease of profoundly dysregulated mineral homeostasis, and thus, changes in bone mineralization and other parameters of bone quality may be expected [Moe et al, 2006, Wolf 2015]. …”

Bone in CKD: why the ERA EDTA CKD-MBD working group organized a dedicated meeting?

“…It is not known how exactly, but an increased expression of sclerostin in bone in early CKD could be responsible of low TO, with or without contribution from uremic toxins. If confirmed, this hypothesis would indicate that adynamic bone is not (or is not necessarily) the result of our inadequate therapies, rather, it would indicate that we need to know when and how this adaptive response becomes maladaptive [6]. This increased importance of early recognition and identification of bone disease rises the need to perform bone biopsies as outlined above, but also prompts renewed efforts for noninvasive identification of ROD types and of fracture risk by means of old and/or new radiologic techniques, as examined in the papers by Jannot et al and by Urena-Torres et al In addition to bone histology and radiological techniques less invasive biochemical assays may assist in diagnosing bone disease in CKD.…”