Phosphate and FGF-23 homeostasis after kidney transplantation

Abstract

Dysregulated phosphate metabolism is a common consequence of chronic kidney disease, and is characterized by a high circulating level of fibroblast growth factor (FGF)-23, hyperparathyroidism, and hyperphosphataemia. Kidney transplantation can elicit specific alterations to phosphate metabolism that evolve over time, ranging from severe hypophosphataemia (<0.5 mmol/l) to hyperphosphataemia (>1.50 mmol/l) and high FGF-23 levels. The majority of renal transplant recipients develop hypophosphataemia during the first 3 months after transplantation as a consequence of relatively slow adaptation of FGF-23 and parathyroid hormone levels to restored renal function, and the influence of immunosuppressive drugs. By 3-12 months after transplantation, phosphate homeostasis is at least partially restored in the majority of recipients, which is paralleled by a substantially reduced risk of cardiovascular-associated morbidity and mortality compared with the pre-transplantation setting. Many renal transplant recipients, however, exhibit persistent abnormalities in phosphate homeostasis, which is often due to multifactorial causes, and may contribute to adverse outcomes on the cardiovascular system, kidney, and bone. Dietary and pharmacologic interventions might improve phosphate homeostasis in renal transplant recipients, but additional insight into the pathophysiology of transplantation-associated abnormalities in phosphate homeostasis is needed to further optimize disease management and improve prognosis for renal transplant recipients.

Timing of Parathyroidectomy Does Not Influence Renal Function After Kidney Transplantation

“…Despite the larger sample size in our study We found that pre-PTx PTH levels were significantly lower in the group of patients who underwent PTx after KTx. This could be partly explained by improved renal function resulting in at least partly restored mineral homeostasis [23]. Alternatively, the difference in pre-KTx PTH values could result from the fact that patients with more severe HPT were more likely to undergo PTx prior to receiving a kidney transplant.…”

Bone health in chronic kidney disease‐mineral and bone disorder: a clinical case seminar and update

“…It acts on the sodium phosphate transporters in the renal tubules to promote phosphaturia and inhibits the action of 1-alpha hydroxylase, further reducing 1, 25-hydroxyvitamin D levels, with an additive effect of potentiating SHPT. 13 Prolonged stimulation of the parathyroid glands may lead to tertiary hyperparathyroidism as a result of parathyroid tissue hyperplasia and downregulation of the calcium-sensing and vitamin D receptors. 14 This is a state of autonomously functioning parathyroid glands without appropriate responsiveness to plasma calcium concentrations.…”

“…FGF‐23 is a phosphaturic hormone secreted by osteocytes, rising early in the development of CKD in response to phosphate retention. It acts on the sodium phosphate transporters in the renal tubules to promote phosphaturia and inhibits the action of 1‐alpha hydroxylase, further reducing 1, 25‐hydroxy‐vitamin D levels, with an additive effect of potentiating SHPT . Prolonged stimulation of the parathyroid glands may lead to tertiary hyperparathyroidism as a result of parathyroid tissue hyperplasia and downregulation of the calcium‐sensing and vitamin D receptors .…”

Response of fibroblast growth factor 23 to volume interventions in arterial hypertension and diabetic nephropathy

“…[3,18–21] In these observational studies, FGF-23 was more compellingly associated with acute heart failure than with atherosclerotic events. Given the consistent associations between FGF-23 and markers of volume status in previous studies, [22–24] and the implicated role for FGF-23 in volume homeostasis, [11,13,22] we sought to investigate whether, conversely, an acute increase in volume status influences FGF-23 concentrations. We found that acute expansion of extracellular volume by sodium-chloride infusion did not reduce FGF-23 concentrations in patients with arterial hypertension.…”