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FGF-23 has arisen as an early biomarker of renal dysfunction, but at the onset of chronic kidney disease (CKD) data suggest that FGF-23 may be produced independently of the parathyroid hormone (PTH), 1,25(OH) -Vitamin D signaling axis. Iron status is inversely correlated to the level of circulating FGF-23, and improvement in iron bioavailability within patients correlates with a decrease in FGF-23. Alternately, recent evidence also supports a regulatory role of inflammatory cytokines in the modulation of FGF-23 expression. To determine the identity of the signal from the kidney inducing upregulation of osteocytic FGF-23 at the onset of CKD we utilized a mouse model of congenital CKD that fails to properly mature the glomerular capillary tuft. We profiled the sequential presentation of indicators of renal dysfunction, phosphate imbalance, and iron bioavailability and transport to identify the events that initiate osteocytic production of FGF-23 during the onset of CKD. We report here that elevations in circulating intact-FGF-23 coincide with the earliest indicators of renal dysfunction (P14), and precede changes in serum phosphate or iron homeostasis. Serum PTH was also not changed within the first month. Instead, production of the inflammatory protein IL-1β from the kidney and systemic elevation of it in the circulation matched the induction of FGF-23. IL-1β's ability to induce FGF-23 was confirmed on bone chips in culture, and within mice in vivo. Furthermore, neutralizing antibody to IL-1β blocked FGF-23 expression in both our congenital model of CKD and a second nephrotoxic serum-mediated model. We conclude that early CKD resembles a situation of primary FGF-23 excess mediated by inflammation. These findings do not preclude that altered mineral availability or anemia can later modulate FGF-23 levels, but find that in early CKD they are not the driving stimulus for the initial upregulation of FGF-23. This article is protected by copyright. All rights reserved.
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The role of monocyte lymphocyte ratio (MLR) in predicting the risk of chronic kidney disease (CKD) is unclear, although inflammation contributes to the development of CKD. This study aimed to investig...
Both chronic kidney disease (CKD) and kidney stones are major public health problems, which are closely interrelated. Recurrent kidney stones predispose to CKD although CKD seems to decrease risk of f...
In recent years, the use of proton pump inhibitors (PPI), especially omeprazole, has been associated with development of chronic kidney disease (CKD). These drugs are widely used worldwide. Although s...
Patients with chronic kidney disease (CKD) bear a substantial burden of comorbidities leading to the prescription of multiple drugs and a risk of polypharmacy. However, data on medication use in this ...
Higher statin intensity is associated with a lower risk of mortality in patients with cardiovascular disease. However, little is known about the relationship between statin intensity and chronic kidne...
The purpose of this study is to demonstrate that once weekly and once every-2-weeks treatment with epoetin alfa, a drug that increases red blood cell production, in patients with anemia as...
Protein energy wasting is an independent factor associated with morbi-mortality in chronic kidney disease. Wasting is particularly common in chronic diseases of organs such as kidney disea...
The purpose of this study is to learn more about how the kidneys control the blood levels of phosphorus in patients with early chronic kidney disease. The ultimate goal is to use this inf...
Foot ulceration is a risk factor that has been associated with early death in patients with chronic kidney disease. Little is known about the relationship between these risk factors that d...
The investigators aimed to evaluate the association between the duration and stage of acute kidney injury (AKI) and the development of chronic kidney disease during postoperative three yea...
Conditions in which the KIDNEYS perform below the normal level for more than three months. Chronic kidney insufficiency is classified by five stages according to the decline in GLOMERULAR FILTRATION RATE and the degree of kidney damage (as measured by the level of PROTEINURIA). The most severe form is the end-stage renal disease (CHRONIC KIDNEY FAILURE). (Kidney Foundation: Kidney Disease Outcome Quality Initiative, 2002)
The end-stage of CHRONIC RENAL INSUFFICIENCY. It is characterized by the severe irreversible kidney damage (as measured by the level of PROTEINURIA) and the reduction in GLOMERULAR FILTRATION RATE to less than 15 ml per min (Kidney Foundation: Kidney Disease Outcome Quality Initiative, 2002). These patients generally require HEMODIALYSIS or KIDNEY TRANSPLANTATION.
Mice selectively bred for hypersusceptibility to two-stage chemical skin carcinogenesis. They are also hypersusceptible to UV radiation tumorigenesis with single high-dose, but not chronic low-dose, exposures. SENCAR (SENsitive to CARcinogenesis) mice are used in research as an animal model for tumor production.
Decalcification of bone or abnormal bone development due to chronic KIDNEY DISEASES, in which 1,25-DIHYDROXYVITAMIN D3 synthesis by the kidneys is impaired, leading to reduced negative feedback on PARATHYROID HORMONE. The resulting SECONDARY HYPERPARATHYROIDISM eventually leads to bone disorders.
Rheumatoid arthritis of children occurring in three major subtypes defined by the symptoms present during the first six months following onset: systemic-onset (Still's Disease, Juvenile-Onset), polyarticular-onset, and pauciarticular-onset. Adult-onset cases of Still's disease (STILL'S DISEASE, ADULT-ONSET) are also known. Only one subtype of juvenile rheumatoid arthritis (polyarticular-onset, rheumatoid factor-positive) clinically resembles adult rheumatoid arthritis and is considered its childhood equivalent.
Nephrology - kidney function
Nephrology is a specialty of medicine and pediatrics that concerns itself with the study of normal kidney function, kidney problems, the treatment of kidney problems and renal replacement therapy (dialysis and kidney transplantation). Systemic conditions...