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Managing mineral bone disease (MBD) could reduce cardiovascular risk and improve the survival of dialysis patients. Our study focuses on the impact of calcium bath exposure in dialysis patients by comparing peritoneal dialysis patients (PD, intervention group) and hemodialysis patients (HD, control group). We assessed various factors, including calcium, phosphorus, magnesium, PTH, vitamin D 25-OH, C-terminal telopeptide (CTX), and FGF-23 levels, as well as the calcium bath six hours before the blood sample and the length of daily calcium exposure. We enrolled 40 PD and 31 HD patients with a mean age of 68.7 ± 13.6 years. Our cohort had median PTH and FGF-23 levels of 194 ng/L (Interquartile range [IQR] 130-316) and 1296 pg/mL (IQR 396-2698), respectively. We identified the length of exposure to a 1.25 mmol/L calcium bath, phosphate levels, and CTX as independent predictors of PTH (OR 0.279, p = 0.011; OR 0.277, p = 0.012; OR 0.11, p = 0.01, respectively). In contrast, independent predictors of FGF-23 were phosphate levels (OR 0.48, p < 0.001) and serum calcium levels (OR 0.25, p = 0.015), which were affected by the calcium bath. These findings suggest that managing dialysate calcium baths impacts phosphaturic hormones and could be a critical factor in optimizing CKD-MBD treatment in PD patients, sparking a new avenue of research and potential interventions.

Phosphaturic mesenchymal tumors (PMT) are rare neoplasms, which can give rise to a multifaceted syndrome, otherwise called tumor-induced osteomalacia (TIO). Localizing these tumors is crucial to obtain a cure for the phosphate metabolism derangement, which is often the main cause leading the patient to seek medical help, because of invalidating physical and neuromuscular symptoms. A proportion of these tumors is completely silent and may grow unnoticed, unless they become large enough to produce pain or discomfort. FGF-23 can be produced by several benign or malignant PMTs. The phosphate metabolism, radiology and histology of these rare tumors must be collectively assessed by a multidisciplinary team aimed at curing the disease locally and improving patients’ quality of life. This narrative review, authored by multiple specialists of a tertiary care hospital center, will describe endocrine, radiological and histological features of these tumors, as well as present surgical and interventional strategies to manage PMTs.

Asymmetric dimethylarginine (ADMA) is a marker of endothelial damage. Research confirms the association of ADMA with an increased cardiovascular risk (CVR) among kidney transplant recipients (KTRs). Additionally, increased circulating levels of fibroblast growth factor 23 (FGF-23) are associated with pathological cardiac remodeling and vascular alterations. The aim of the study is the analysis of the relationship between ADMA, FGF-23, nutritional, biochemical parameters in healthy subjects and KTRs. 46 KTRs and 23 healthy volunteers at mean age of 50.8 ± 15.4 and 62.5 ± 10.7 years were enrolled. The anthropometric and biochemical parameters such as ADMA, FGF-23, albumin, prealbumin were assessed. Fat tissue mass among KTRs was 30.28 ± 9.73%, lean body mass 64.5 ± 14.8%. Overweight and obesity was presented by 65.2% of recipients. Albumin level was 38.54 ± 3.80 g/L, prealbumin 27.83 ± 7.30 mg/dL and were significantly lower than in the control (p < 0.05). Patients with ADMA > 0.66 µmol/L had a lower concentration of prealbumin, albumin and increased concentration of oxidized low density lipoprotein (oxLDL), high sensitive C-reactive protein (hsCRP) and FGF-23. FGF-23 was significantly higher in patients with higher hsCRP (p < 0.05). KTRs with elevated ADMA had a longer transplantation vintage, lower eGFR and higher albuminuria. Diabetes mellitus (DM) was associated with higher levels of ADMA and FGF-23. Even in stable KTRs a relationship between inflammatory state, nutritional status, graft function and endothelial dysfunction biomarkers was observed.

Fibroblast growth factor-23 (FGF-23) is a phosphaturic hormone used to monitor chronic kidney disease (CKD) in humans. The aims of this study were (1) to determine the intra- and interassay precision of the FGF-23 concentrations in dogs as measured via the Kainos ELISA FGF-23 kit, (2) to calculate a reference interval, and (3) to assess the correlation of the FGF-23 concentration with the hematological and biochemical parameters. The coefficient of variation was below 15% for both the intra- and interassay precision, indicating good reproducibility. The reference interval ranged between 95.8 (90% confidence interval: 44.6; 139.2) and 695.1 pg/mL (598.7; 799.1) based on 136 clinically healthy dogs, classified as such according to the information of treating veterinarians as well as the unremarkable results of hematology and biochemistry. The FGF-23 concentration differed significantly between dogs aged p = 0.045). Four groups of 10 dogs each were retrospectively formed based on the creatinine concentration classification according to the IRIS staging. Correlation was the strongest for the renal parameters. Statistically significant differences in the FGF-23 concentration were demonstrated between the study groups I and III (p < 0.001), I and IV (p < 0.001), and II and IV (p = 0.005). There was a trend for a rising FGF-23 concentration in older dogs. Due to the wide reference interval, diagnostic cut-offs and/or subject-based FGF-23 reference values in each dog are needed for monitoring and clinical interpretation.

Managing mineral bone disease (MBD) could reduce cardiovascular risk and improve the survival of dialysis patients. Our study focuses on the impact of calcium bath exposure in dialysis patients by comparing peritoneal dialysis patients (PD, intervention group) and hemodialysis patients (HD, control group). We assessed various factors, including calcium, phosphorus, magnesium, PTH, vitamin D 25-OH, C-terminal telopeptide (CTX), and FGF-23 levels, as well as the calcium bath six hours before the blood sample and the length of daily calcium exposure. We enrolled 40 PD and 31 HD patients with a mean age of 68.7 ± 13.6 years. Our cohort had median PTH and FGF-23 levels of 194 ng/L (Interquartile range [IQR] 130-316) and 1296 pg/mL (IQR 396-2698), respectively. We identified the length of exposure to a 1.25 mmol/L calcium bath, phosphate levels, and CTX as independent predictors of PTH (OR 0.279, p = 0.011; OR 0.277, p = 0.012; OR 0.11, p = 0.01, respectively). In contrast, independent predictors of FGF-23 were phosphate levels (OR 0.48, p < 0.001) and serum calcium levels (OR 0.25, p = 0.015), which were affected by the calcium bath. These findings suggest that managing dialysate calcium baths impacts phosphaturic hormones and could be a critical factor in optimizing CKD-MBD treatment in PD patients, sparking a new avenue of research and potential interventions.

Background: Fibroblast growth factor-23 (FGF-23) associates with decreased kidney function in patients with chronic kidney disease (CKD). However, the correlation between circulating FGF-23 levels and the rate of renal function decline in healthy individuals is largely unknown. We aimed to evaluate the predictive performance of FGF-23 for rapid kidney function decline (RKFD) in a community-based study. Methods: A total of 2963 people residing in northern Taiwan were enrolled from August 2013 to May 2018 for an annual assessment of kidney function for five years. The baseline estimated glomerular filtration rates (eGFR) were calculated using the 2009 and 2021 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation, which aggregates the values of serum creatinine and cystatin C (eGFRcr-cys). The outcome was RKFD—a 15% decrease in estimated glomerular filtration rate (eGFR) within the first four years, and a reduction in eGFR without improvement in the 5th year. A generalized additive model (GAM) was used to determine the cut-off value of FGF-23 to predict RKFD. Results: The incidence of RKFD was 18.0% (114/634). After matching for age and sex at a 1:1 ratio, a total of 220 subjects were analyzed. eGFRcr-cys was negatively correlated with total vitamin D level but seemed irrelevant to FGF-23. Multivariable logistic regression analysis showed that FGF-23, eGFRcr-cys, and urine albumin-to-creatinine ratio (UACR) were independent predictors of the possibility of RKFD. FGF-23 showed the best predictive performance for RKFD (AUROC: 0.803), followed by baseline eGFRcr-cys (AUROC: 0.639) and UACR (AUROC: 0.591). From the GAM, 32 pg/mL was the most appropriate cut-off value of FGF-23 with which to predict RKFD. The subgroup and sensitivity analyses showed consistent results that high-FGF-23 subjects had higher risks of RKFD. Conclusions: Circulating FGF-23 level could be a helpful predictor for RKFD in this community-based population.

There is a reduced intake of selenium in many countries due to low levels of selenium in the soil. This results in an increased cardiovascular risk. Fibroblast growth factor 23 (FGF-23) is active mainly in the metabolism of vitamin D and phosphorus. However, there are indications that FGF-23 may also provide information both on cardiovascular function and prognosis. The aim of the study was to evaluate the effect of supplementation with selenium and coenzyme Q10 on the FGF-23 concentration in an elderly population with low concentrations of both selenium and coenzyme Q10 and in which the supplementation improved cardiac function and mortality. In a randomised double-blind placebo-controlled trial, FGF-23 was measured in 219 individuals at the start and after 48 months. Selenium yeast (200 µg/day) and coenzyme Q10 (200 mg/day) (n = 118) or placebo (n = 101) were given as a dietary supplement. The intervention time was 48 months. t-Tests, repeated measures of variance, and ANCOVA analyses were used to evaluate the differences in FGF-23 concentration. Following supplementation with selenium and coenzyme Q10, a significantly lower level of FGF-23 could be seen (p = 0.01). Applying 10 years of follow-up, those who later died a cardiovascular death had a significantly higher FGF-23 concentration after 48 months compared with those who survived (p = 0.036), and a significantly lower FGF-23 concentration could be seen in those with a normal renal function compared to those with an impaired renal function (p = 0.027). Supplementation with selenium and coenzyme Q10 to an elderly community-living population low in both substances prevented an increase of FGF-23 and also provided a reduced cardiovascular risk.

Rickets refers to a deficient mineralization of the growth plate cartilage, predominantly affecting longer bones. Despite the fact that preventive measures are available, it is still a common disease worldwide; nutritional rickets, due to vitamin D deficiency or dietary calcium inadequate intake, remains the most common form. Medical history, physical examination, radiologic features and biochemical tests are essential for diagnosis. Although recent studies suggest hypophosphatemia as the leading alteration, rickets is classically divided into two categories: calcipenic rickets and phosphopenic rickets. Knowledge of this categorization and of respective clinical and laboratory features is essential for rapid diagnosis and correct management. The aim of this review is to analyze the epidemiological, pathogenetic, clinical, and therapeutic aspects of the different forms of rickets, describing the novelties on this “long-lived” disease.

A possible cause of hypophosphatemia is paraneoplastic secretion of fibroblast growth factor 23 (FGF-23). Tumors secreting FGF-23 are rare, mostly of mesenchymal origin, usually benign, and may be located anywhere in the body, including hands and feet, which are often not represented in conventional imaging. A 50-year-old woman presented with diffuse musculoskeletal pain and several fractures. Secondary causes of osteoporosis were excluded. Laboratory analysis revealed hypophosphatemia and elevated alkaline phosphatase, parathyroid hormone, and FGF-23. Thus, oncogenic osteomalacia due to neoplastic FGF-23 secretion was suspected. FDG-PET-CT and DOTATATE-PET-CT imaging demonstrated no tumor. Cranial MRI revealed a tumorous mass in the left cellulae ethmoidales. The tumor was resected and histopathological examination showed a cell-rich tumor with round to ovoid nuclei, sparse cytoplasm, and sparse matrix, resembling an olfactory neuroblastoma. Immunohistochemical analysis first led to diagnosis of olfactory neuroblastoma, which was later revised to phosphaturic mesenchymal tumor. Following the resection, FGF-23 and phosphate levels normalized. In conclusion, we here describe a patient with an FGF-23-secreting phosphaturic mesenchymal tumor with an unusual morphology. Furthermore, we emphasize diagnostic pitfalls when dealing with FGF-23-induced hypophosphatemia.

Background: The diagnosis of phosphaturic mesenchymal tumors (PMT) is easily delayed clinically, and their surgical treatment is unstandardized. This study aimed to evaluate our experience in the diagnosis and treatment of PMT and provide a research basis for the accurate and standardized treatment of PMT., Materials and Methods: Twelve patients diagnosed with PMT in our department and who underwent surgical treatment were included in this study. Preoperative demographic and clinical information were recorded. CT, MRI, and technetium-99m (Tc99m)-octreotide PET/CT imaging techniques were used to evaluate the general conditions and lesion boundaries of the tumors. Surgical treatment was performed using radical resection and microwave ablation-assisted extended curettage according to the lesion location and size. Patients were strictly followed up with and evaluated for oncological prognosis, radiological results, bone healing, serum ion levels, limb function, and pain level; the occurrence of complications was also recorded., Results: Three patients underwent radical resection, and nine underwent microwave ablation-assisted extended curettage. The average duration of symptoms in this group was 1.5 years (9-35 months) before diagnosis. Serum phosphate and AKP levels returned to normal one and two weeks postoperatively, respectively. There was no apparent specificity in the pathological findings; however, the immunohistochemistry of FGF-23 was positive, and the original fracture sites were effectively healed during the follow-up. The limb function and pain scores were significantly improved. The MSTS score increased from 15.3 to 29.0, and the VAS score decreased from 5.3 to 0.4. All patients recovered, and 90% resumed their original jobs., Conclusions: Accurate diagnosis and standardized surgical treatment are crucial to achieving a clinical cure for PMT. Combining clinical manifestations, biochemical examinations, imaging characteristics, and pathological findings is an effective way to diagnose PMT accurately. Radical resection and microwave ablation-assisted extended curettage are reliable surgical treatment methods for PMT.

The purpose of this study was to assess the clinical usefulness of assaying the fibroblast growth factor (FGF-23), Klotho, osteocalcin, N-terminal telopeptide of type I collagen (NTX), and sclerostin levels in patients with primary hyperparathyroidism (PHPT) as markers of bone damage as well as for surgical treatment success. Seventeen patients with hypercalcemic PHPT and normal kidney function were studied. In all patients, PTH (parathormone), serum calcium, and creatinine were performed before and six months after parathyroidectomy (PTX). The studied group included patients whose PTH and calcium concentrations normalized post-operatively and with confirmed histopathological diagnosis. The control group consisted of nine age-matched healthy volunteers. The PHPT patients had elevated concentrations of FGF-23, osteocalcin, and NTX and reduced levels of sclerostin, as compared to the control group. After PTX, osteocalcin, NTX, and sclerostin levels normalized. The plasma values of FGF-23 decreased significantly, but remained higher than in healthy subjects. Serum Klotho protein levels did not differ significantly in the two groups. These results suggest that osteocalcin and NTX may potentially be considered as markers of PHPT progression. Additionally, serum normalization of osteocalcin, NTX, and sclerostin might be considered as indicators of PTX success. On the other hand, FGF-23 can represent a parameter reflecting the degree of calcium-phosphate imbalance in PHPT patients, but its usefulness in monitoring the effects of PTX requires further research. The clinical utility of assaying Klotho in PHPT remains to be confirmed.

Rickets refers to a deficient mineralization of the growth plate cartilage, predominantly affecting longer bones. Despite the fact that preventive measures are available, it is still a common disease worldwide; nutritional rickets, due to vitamin D deficiency or dietary calcium inadequate intake, remains the most common form. Medical history, physical examination, radiologic features and biochemical tests are essential for diagnosis. Although recent studies suggest hypophosphatemia as the leading alteration, rickets is classically divided into two categories: calcipenic rickets and phosphopenic rickets. Knowledge of this categorization and of respective clinical and laboratory features is essential for rapid diagnosis and correct management. The aim of this review is to analyze the epidemiological, pathogenetic, clinical, and therapeutic aspects of the different forms of rickets, describing the novelties on this "long-lived" disease.

α-Klotho is a known anti-aging protein that exerts diverse physiological effects, including phosphate homeostasis. Klotho expression occurs predominantly in the kidney and is significantly decreased in patients with chronic kidney disease. However, changes in serum klotho levels and impacts of klotho on outcomes among kidney transplant (KTx) recipients and kidney donors remain unclear. A literature search was conducted using MEDLINE, EMBASE, and Cochrane Database from inception through October 2019 to identify studies evaluating serum klotho levels and impacts of klotho on outcomes among KTx recipients and kidney donors. Study results were pooled and analyzed utilizing a random-effects model. Ten cohort studies with a total of 431 KTx recipients and 5 cohort studies with a total of 108 living kidney donors and were identified. After KTx, recipients had a significant increase in serum klotho levels (at 4 to 13 months post-KTx) with a mean difference (MD) of 243.11 pg/mL (three studies; 95% CI 67.41 to 418.81 pg/mL). Although KTx recipients had a lower serum klotho level with a MD of = -234.50 pg/mL (five studies; 95% CI -444.84 to -24.16 pg/mL) compared to healthy unmatched volunteers, one study demonstrated comparable klotho levels between KTx recipients and eGFR-matched controls. Among kidney donors, there was a significant decrease in serum klotho levels post-nephrectomy (day 3 to day 5) with a mean difference (MD) of -232.24 pg/mL (three studies; 95% CI -299.41 to -165.07 pg/mL). At one year following kidney donation, serum klotho levels remained lower than baseline before nephrectomy with a MD of = -110.80 pg/mL (two studies; 95% CI 166.35 to 55.24 pg/mL). Compared to healthy volunteers, living kidney donors had lower serum klotho levels with a MD of = -92.41 pg/mL (two studies; 95% CI -180.53 to -4.29 pg/mL). There is a significant reduction in serum klotho levels after living kidney donation and an increase in serum klotho levels after KTx. Future prospective studies are needed to assess the impact of changes in klotho on clinical outcomes in KTx recipients and living kidney donors.