scholarly journals Μελέτη της παθογένειας των αγγειακών αλλοιώσεων και των διαταραχών οστικού μεταβολισμού σε ασθενείς με χρόνια νεφρική νόσο τελικού σταδίου

2013 ◽  
Author(s):  
Παναγιώτης Πατεινάκης
Keyword(s):  
Standard Beta ◽  
Fgf 23

Σκοπός της παρούσας μελέτης ήταν η διερεύνηση σε αιμοκαθαιρόμενους ασθενείς της συσχέτισης των επιπέδων στον ορό της φετουΐνης-Α, της οστεοπροτεγερίνης και του FGF-23, με τη σκλήρυνση του αρτηριακού τοιχώματος και την αρχόμενη αθηροσκλήρωση.Στη μελέτη εντάχθηκαν 81 ασθενείς υπό χρόνια αιμοκάθαρση. Τα επίπεδα φετουΐνης-Α, οστεοπροτεγερίνης, άθικτου μορίου FGF-23 (iFGF-23) και καρβοξυτελικού τμήματος (cFGF-23) προσδιορίστηκαν στον ορό με ανοσοενζυμική μέθοδο. Η σκλήρυνση του αρτηριακού τοιχώματος εκτιμήθηκε με τη μέτρηση της ταχύτητας αγωγής σφυγμικού κύματος (PWV) μεταξύ καρωτίδας και μηριαίας αρτηρίας. Η αρχόμενη αθηροσκλήρωση εκτιμήθηκε με την υπερηχογραφική μέτρηση του πάχους του έσω-μέσου χιτώνα (ΙΜΤ) της κοινής καρωτίδας. Η PWV παρουσίασε αρνητική συσχέτιση με την φετουΐνη-Α (p=0,001), και θετική με την οστεοπροτεγερίνη (p=0,000), ενώ δεν παρουσίασε γραμμική συσχέτιση με τα επίπεδα cFGF-23 και iFGF-23. Σε μοντέλο πολλαπλής γραμμικής παλινδρόμησης, τόσο η φετουΐνη-Α όσο και η οστεοπροτεγερίνη παρουσίασαν ανεξάρτητη συσχέτιση με την PWV (p=0,032, standard beta=-0197 και p=0,041, standard beta=0,227 αντίστοιχα). Σε υποομάδα 59 ασθενών χωρίς στεφανιαία νόσο ταχύτητες αγωγής σφυγμικού κύματος < 9,1m/sec, και >11,1m/sec παρουσίασαν θετική συσχέτιση με τα επίπεδα iFGF-23 (p=0,032), η οποία στην πολυπαραγοντική ανάλυση ήταν ανεξάρτητη από την ηλικία, την παρουσία σακχαρώδους διαβήτου, την πίεση σφυγμού και τα επίπεδα φετουΐνης-Α, οστεοπροτεγερίνης (p=0.049). Στη μονοπαραγοντική ανάλυση το ΙΜΤ παρουσίασε αρνητική συσχέτιση με την φετουΐνη-Α (p=0,005), και θετική με την οστεοπροτεγερίνη (p=0,000). Οι συσχετίσεις όμως αυτές δεν ήταν ανεξάρτητες από την ηλικία. Το ΙΜΤ δεν παρουσίασε γραμμική συσχέτιση με τα επίπεδα cFGF-23 και iFGF-23. Όμως υψηλότερα από το μέσο όρο επίπεδα iFGF-23 συσχετίσθηκαν με υψηλότερες τιμές ΙΜΤ (p=0,035). Η συσχέτιση αυτή ήταν ανεξάρτητη από την ηλικία. Στην πολυπαραγοντική ανάλυση ανεξάρτητη συσχέτιση με το ΙΜΤ παρουσίασαν η ηλικία (p=0,000, standard beta=0,570), η παρουσία καρδιαγγειακής νόσου (p=0,031, standard beta=0,166), και τα υψηλότερα σε σχέση με το μέσο όρο επίπεδα iFGF-23 (p=0,028, standard beta=0,164). Σε μοντέλο που περιελάμβανε μόνο τους ορολογικούς δείκτες που συσχετίσθηκαν με το ΙΜΤ ανεξάρτητη συσχέτιση με το ΙΜΤ παρουσίασαν η οστεοπροτεγερίνη (p=0.000, standard beta=0,420), τα επίπεδα iFGF-23 (p=0.016, standard beta=0,232) και η φετουΐνη-Α (p=0.032, standard beta=-0,223). Συμπερασματικά σε ασθενείς υπό χρόνια αιμοκάθαρση η φετουΐνη-Α και η οστεοπροτεγερίνη παρουσίασαν ανεξάρτητη γραμμική συσχέτιση, αρνητική και θετική αντίστοιχα, με τη σκλήρυνση του αρτηριακού τοιχώματος, ως ταχύτητα αγωγής σφυγμικού κύματος (PWV). Η συσχέτισή τους με την αρχόμενη αθηροσκλήρωση ως πάχυνση του αρτηριακού τοιχώματος (IMT) δεν ήταν ανεξάρτητη από την ηλικία.

scholarly journals THU0421 TUMOR-INDUCED OSTEOMALACIA: DATA FROM A MONOCENTRIC EXPERIENCE ON 16 PATIENTS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 448.2-449
Author(s):  
C. Crotti ◽  
F. Bartoli ◽  
M. Manara ◽  
P. A. Daolio ◽  
F. Zucchi ◽  
...  
Keyword(s):  
Functional Imaging ◽  
Serum Alkaline Phosphatase ◽  
Fibroblast Growth Factor 23 ◽  
Diagnostic Delay ◽  
The Body ◽  
Definitive Treatment ◽  
Surgical Removal ◽  
Tumor Biopsy ◽  
Pet Ct ◽  
Fgf 23

Background:Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome due to a phosphaturic tumor, which overproduces fibroblast growth factor-23 (FGF-23), causing hyperphosphaturia, hypophosphoremia, low 1,25(OH)2VitD3and osteomalacia. Locating the tumor is critical, because lesions are typically small, benign mesenchymal tumors, anywhere in the body; the delay between onset of symptoms and diagnosis ranges from 2.5–28 years. Surgical removal is the only effective therapeutic approach.Objectives:To retrospectively evaluate patients affected by TIO, investigating clinical management and disease outcome.Methods:We retrospectively collected data of patients affected by TIO referred to a tertiary Rheumatology Center between Sep 2000 and Jan 2020.Results:We included 16 patients with a definite diagnosis of TIO, mean age±standard deviation 62.4±14.6 yrs, 56.2% females, mean age at symptoms onset 48.0±14.3 yrs (53.8±13.1 at diagnosis). Mean diagnostic delay between symptoms onset and tumor detection was 6.8±6.4 yrs. All patients complained bone pain, muscle weakness, and fractures before diagnosis of TIO. Biochemical findings were: mean serum Phosphorus (PS) 1.4±0.4 mg/dL (reference range (RR) 2.5-4.6), mean serum Calcium 9.4±0.7 mg/dL (RR 8.4-10.2), mean serum 1,25(OH)2VitD330.5±23.4 ng/L (RR 25-86). Intact-FGF-23 was dosed in 9 patients, always resulting elevated: mean 396.6±707.3 pg/mL (RR 25-45). PTH was increased in 30% of cases, while serum alkaline phosphatase was increased in 87.5%. 24h-Urine Phosphorus (PU) was increased in only 13% of patients, but, when renal phosphate wasting by tubular reabsorption of phosphate (TRP) was calculated, PU resulted increased in all.Tumor was localized in all cases (Fig.1) and were localized in bone and soft tissue, by using functional imaging, followed by anatomical techniques. Before the introduction in routinely practice of68Ga-DOTATATE-PET-CT in 2013, Octreoscan-SPECT/CT and18F FDG-PET were used as imaging modalities. Since 2013, diagnostic delay consistently reduced, from 8.6±8.3 yrs (7 patients) to 4.5±2.6 yrs (9 patients), confirming higher diagnostic accuracy of68Ga-DOTATATE-PET-CT.Figure 1.13 patients underwent surgery; in two cases surgery was not possible due to tumor location, so pharmacological support with phosphate supplements and calcitriol was started; a patient underwent to TC-guided radiofrequency ablation. After surgery, 7 patients experienced a complete remission, 3 had a persistence of the disease, and 3 an overtime relapse, even after a longstanding normalization of PS (6 years). After surgical tumor removal, PS significantly increased in few days (from 1.36±0.39 to 2.9±1.1, p=0.0001), while iFGF-23 levels tended to rapidly decreased (from 396.6±707.3 to 62.8±78.4). Before the introduction of68Ga-DOTATATE-PET-CT, 6 patients underwent to imaging-guided closed biopsy to confirm tumor localization; by using68Ga-DOTATATE-PET-CT only 2 subjects had closed biopsy. Furthermore, in our population only patients who had biopsy to detect the lesion (7 patients) had relapses compared to patients who did not.Conclusion:To our knowledge, this is the widest European cohort of patients affected by TIO reported in the last two decades. We confirm an important delay between symptoms onset and diagnosis. To locate tumor, a stepwise approach is recommended, starting with a thorough medical history and physical examination, followed by functional imaging, preferring68Ga-DOTATATE-PET-CT. Tumor biopsy is not recommended due to the potential cell spilling. Surgery is considered the only definitive treatment, aiming to a wider excision. Active surveillance is always needed, due to the possible relapses, even after a long period of complete clinical and biochemical remission.Disclosure of Interests: :Chiara Crotti: None declared, Francesca Bartoli: None declared, Maria Manara Consultant of: Consultant and/or speaker for Eli-Lilly, MSD, Sanofi-Genzyme, Novartis, Alfa Wasserman and Cellgene, Speakers bureau: Consultant and/or speaker for Eli-Lilly, MSD, Sanofi-Genzyme, Novartis, Alfa Wasserman and Cellgene, Primo Andrea Daolio: None declared, Francesca Zucchi: None declared, Roberto Caporali Consultant of: AbbVie; Gilead Sciences, Inc.; Lilly; Merck Sharp & Dohme; Celgene; Bristol-Myers Squibb; Pfizer; UCB, Speakers bureau: Abbvie; Bristol-Myers Squibb; Celgene; Lilly; Gilead Sciences, Inc; MSD; Pfizer; Roche; UCB, Luigi Sinigaglia: None declared, Massimo Varenna: None declared

scholarly journals P043 Fascinating phosphate: seek and you will find

Rheumatology ◽  
2021 ◽  
Vol 60 (Supplement_1) ◽  
Author(s):  
Jyoti Bakshi ◽  
Clare Batten
Keyword(s):  
Back Pain ◽  
Degenerative Change ◽  
Nasal Bone ◽  
Rare Condition ◽  
Whole Body ◽  
Excision Biopsy ◽  
Small Lesion ◽  
History Of ◽  
The Right ◽  
Fgf 23

Abstract Background/Aims  A 62-year-old accountant was referred to the metabolic bone clinic with a 2 year history of thoracic back pain and a persistently raised ALP. There were no associated red flags for her back pain. She had a history of a gluteal lump, thought to be benign, for which she had declined excision. She has hypertension and had a previous navicular fracture. Medications included bendroflumethiazide and Adcal D3. She had restriction in neck movements and was tender to percussion in the thoracic spine. There was no proximal weakness or focal neurology. Systems and joint exam were unremarkable. Methods  The case is discussed below. Results  Salient abnormal results on presentation were a raised ALP of 207 and corrected calcium of 2.34. PTH was elevated at 8.2 (NR:1.6-6.9), Vitamin D 79 and a low phosphate of 0.34 (NR:0.8-1.50). Alkaline phosphatase isoenzymes showed the raised level came from bone. Protein and urine electrophoresis were normal. A bone density scan was normal, and a recent thoracic MRI showed only degenerative change. An isotope bone scan was requested and was reported to show increased activity in the nasal bone, maxilla and both orbits, raising the possibility of Paget’s disease. However, when reviewed in the Radiology meeting with a skull x-ray, the appearances were not felt to be in keeping with Paget’s. Despite physiotherapy, hydrotherapy, acupuncture and neuropathic medication the patient’s back pain continued. Her phosphate remained low and her calculated tubular reabsorption of phosphate from a 24h urine collection (TmP/GFR) was low at 0.42mmol/l (NR 0.80-1.35). She was started on phosphate replacement and calcitriol, and Adcal D3 was continued. The Fibroblast Growth Factor (FGF) 23 levels were sent and came back significantly elevated at 1380 (NR &lt; 100). A 68Ga DOTA-TATE scan (whole body PET/CT scan), confirmed the right gluteal lump as the source of the FGF 23. The patient went on to have an excision biopsy and histology confirmed a mesenchymal tumour of the right buttock. Her phosphate replacement was gradually weaned, but on reducing the dose phosphate levels dropped and her symptoms returned. The repeat TmP/GFR was again low at 0.61, and FGF 23 levels were still raised at 204. A repeat 68Ga DOTA-TATE scan, 4 years after the first one, showed recurrence of the right gluteal lesion and a possible small lesion in the left gluteal muscle. She has been sent for further excision. Conclusion  Tumour induced osteomalacia (TIO) is a rare condition and should be considered in cases of hypophosphataemia. Classical symptoms are proximal weakness and muscle and bone pain. They are typically associated with small benign tumours (most commonly mesenchymal tumours) which may be difficult to find. Excision is curative but if small amounts of tumour remain, relapses may occur. Disclosure  J. Bakshi: None. C. Batten: None.

scholarly journals FGF-23 and Phosphate in Children with Chronic Kidney Disease: A Cross-Sectional Study in Kazakhstan

Medicina ◽  
2020 ◽  
Vol 57 (1) ◽  
pp. 15
Author(s):  
Altynay Balmukhanova ◽  
Kairat Kabulbayev ◽  
Harika Alpay ◽  
Assiya Kanatbayeva ◽  
Aigul Balmukhanova
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Fibroblast Growth Factor 23 ◽  
Cross Sectional Study ◽  
Sectional Study ◽  
Cross Sectional ◽  
Ckd Stage ◽  
Advanced Stages ◽  
Fgf 23 ◽  
Stage 1

Background and objectives: Chronic kidney disease (CKD) in children is a complex medical and social issue around the world. One of the serious complications is mineral-bone disorder (CKD-MBD) which might determine the prognosis of patients and their quality of life. Fibroblast growth factor 23 (FGF-23) is a phosphaturic hormone which is involved in the pathogenesis of CKD-MBD. The purpose of the study was to determine what comes first in children with CKD: FGF-23 or phosphate. Materials and Methods: This cross-sectional study included 73 children aged 2–18 years with CKD stages 1–5. We measured FGF-23 and other bone markers in blood samples and studied their associations. Results: Early elevations of FGF-23 were identified in children with CKD stage 2 compared with stage 1 (1.6 (1.5–1.8) pmol/L versus 0.65 (0.22–1.08), p = 0.029). There were significant differences between the advanced stages of the disease. FGF-23 correlated with PTH (r = 0.807, p = 0.000) and phosphate (r = 0.473, p = 0.000). Our study revealed that the elevated level of FGF-23 went ahead hyperphosphatemia and elevated PTH. Thus, more than 50% of children with CKD stage 2 had the elevating level of serum FGF-23, and that index became increasing with the disease progression and it achieved 100% at the dialysis stage. The serum phosphate increased more slowly and only 70.6% of children with CKD stage 5 had the increased values. The PTH increase was more dynamic. Conclusions: FGF-23 is an essential biomarker, elevates long before other markers of bone metabolism (phosphate), and might represent a clinical course of disease.

scholarly journals P0949EFFECT OF DIETARY PHOSPHORUS RESTRICTION ON FIBROBLAST GROWTH FACTOR,KLOTHO AND BODY COMPOSITION IN CHRONIC KIDNEY DISEASE PATIENTS

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Trisha Sachan ◽  
Anita Saxena ◽  
Amit Gupta
Keyword(s):  
Chronic Kidney Disease ◽  
Body Composition ◽  
Renal Function ◽  
Kidney Disease ◽  
Urinary Protein ◽  
Dietary Phosphorus ◽  
Ckd Stage ◽  
Significant Difference ◽  
The Mean ◽  
Fgf 23

Abstract Background and Aims Changes in dietary phosphorus regulate serum FGF-23, parathyroid hormone, 1,25(OH)(2)D and Klotho concentrations . Cardiovascular disease (CVD) is the principal killer of patients with chronic kidney disease and hyperphosphetemia is a potent risk factor it. Of many causative factors for CVD in CKD, dietary interventions involving restriction of dietary phosphorous intake can help reduce onset of CVD at early stages of CKD with other corrective measures. Muscle wasting is a consequence of uremic syndrome which alters body composition. The aim of the study was to study effect of dietary phosphorous restriction on FGF-23, iPTH, Klotho, 1,25(OH)(2)D and body composition in chronic kidney disease patients. Method This is a longitudinal study with 12 months intervention, approved by Ethics Committee of the institute. A total 132 subjects were recruited (66 healthy controls, 66 CKD patient. of 66 patients 33 were in CKD stage 1 and 33 in stage 2. GFR was calculated with the help of MDRD formula. Biochemical parameters of subjects were evaluated at baseline, 6 and 12 months along with the anthropometric measurements (body weight, height, mid upper arm circumference (MUAC), and skin folds). Three days dietary recall was taken to evaluate energy, protein and phosphorous intake. CKD patients whose dietary phosphorous intake was more than 1000 mg/day, were given intense dietary counseling and prescribed dietary modifications by restricting dietary phosphorous between 800-1000 mg/day. Results The mean age of controls and patients was 37.01±9.62 and 38.27±12.06 and eGFR of 136.94±11.77 and 83.69±17.37 respectively. One way ANOVA showed significant difference among controls and the study groups in hemoglobin (p&lt;0.001), s albumin (p&lt;0.001), FGF-23 (p&lt;0.001), klotho (p&lt;0.001), urinary protein (p&lt;0.001) and Nephron Index (p&lt;0.001).The mean energy intake (p = 0.001) and dietary phosphorous intake (p&lt;0.001) of the CKD patients decreased significantly with the decline in the renal function along with the anthropometric measures i.e. BMI (p = 0.041),WHR (p = 0.015) and all four skin folds (p&lt;0.001). On applying Pearson’s correlation, eGFR correlated negatively with urinary protein (-0.739, 0.000), FGF-23 (-0.679, 0.000) and serum phosphorous (-0.697, 0.000) and positively with klotho (0.872, 0.000). FGF-23 correlated negatively with klotho (-0.742, 0.000). Dietary phosphorous was found to be positively correlated with urinary protein (0.496, 0.000), serum phosphorous (0.680, 0.000) and FGF-23 (0.573, 0.000) and negatively with Klotho (-0.602, 0.000). Nephron index revealed a positive correlation with eGFR (0.529, 0.000). Urinary protein correlated negatively with klotho (-0.810, 0.000). A multiple linear regression was run to predict eGFR from anthropometric variables such as BMI, WHR, MUAC, skin folds thickness and handgrip strength. All anthropometric variables predicted decline in eGFR (p&lt;0.05, R2 =0.223). At 6 and 12 months; repeated ANOVAs analysis showed a statistically significant difference in serum creatinine (p=0.000), serum phosphorous (p=0.000), FGF-23(p=0.000) and klotho (p=0.000). Conclusion Elevated levels of FGF-23 and decreased Klotho levels, with the moderate decline in renal function improved with the restricted phosphorous diet at 6 and 12 months emphasizing the importance of phosphorus restriction at an early stage.

scholarly journals Increased Levels of sRAGE in Diabetic CKD-G5D Patients: A Potential Protective Mechanism against AGE-Related Upregulation of Fibroblast Growth Factor 23 and Inflammation

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Elena Dozio ◽  
Valentina Corradi ◽  
Elena Vianello ◽  
Elisa Scalzotto ◽  
Massimo de Cal ◽  
...  
Keyword(s):  
Cardiovascular Risk ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Cardiac Remodeling ◽  
Glycated Albumin ◽  
Fibroblast Growth Factor 23 ◽  
Protective Mechanism ◽  
Fibroblast Growth ◽  
Increased Risk ◽  
Fgf 23

Advanced glycation end products (AGEs) may induce cardiac remodeling in kidney disease by promoting fibroblast growth factor 23 (FGF-23) expression. Since AGEs are increased in diabetes mellitus (DM), our first aim was to evaluate the existence of any potential association between AGEs, FGF-23, inflammation, and increased cardiovascular risk in DM patients on dialysis (CKD-G5D). Secondarily, we explored the potential role of the soluble receptor for AGEs (sRAGE) as a marker of heart failure. Levels of glycated albumin (GA), sRAGE, c-terminal FGF-23 (cFGF-23), brain natriuretic peptide (BNP), and inflammatory mediators were compared between DM and non-DM CKD-G5D patients. The levels of sRAGE, cFGF-23, BNP, and proinflammatory markers were over the ranges of normality in both DM and non-DM groups. Only GA and sRAGE levels were increased in DM compared to non-DM patients. Plasma levels of sRAGE and CRP were the only independent predictors of BNP concentration. In conclusion, in DM CKD-G5D patients, sRAGE appeared to be a marker of cardiac remodeling. Indeed, its increase could be a potential protective mechanism against the increased risk of cardiovascular complications related to AGEs and inflammation. The causal relationship between sRAGE and cardiovascular risk in these patients needs to be further confirmed by mechanistic studies.

Cinacalcet lowers FGF-23 level together with bone metabolism in hemodialyzed patients with secondary hyperparathyroidism

2011 ◽  
Vol 44 (5) ◽  
pp. 1479-1486 ◽  
Author(s):  
Tomasz Hryszko ◽  
Szymon Brzosko ◽  
Alicja Rydzewska-Rosolowska ◽  
Ewa Koc-Zorawska ◽  
Michal Mysliwiec
Keyword(s):  
Secondary Hyperparathyroidism ◽  
Bone Metabolism ◽  
Fgf 23
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