scholarly journals Assessment of the Concentration of Bone Metabolism Markers: Sclerostin and FGF-23 in Children with Idiopathic Nephrotic Syndrome Treated with Glucocorticosteroids

2019 ◽  
Vol 2019 ◽  
pp. 1-7 ◽  
Author(s):  
Agnieszka Pukajło-Marczyk ◽  
Anna Jakubowska ◽  
Agnieszka Bargenda-Lange ◽  
Katarzyna Kiliś-Pstrusińska ◽  
Danuta Zwolińska

Recurring nature of idiopathic nephrotic syndrome (INS) and steroid dependence imply a long-term treatment with glucocorticosteroids (GCSs), which increases the risk of bone metabolism disorders. The search for new markers of that process is essential. The aims of this study were to assess the concentrations of sclerostin (Scl) and fibroblast growth factor-23 (FGF-23) in the plasma of children with INS and compare Scl and FGF-23 to existing markers of bone metabolism, mainly parathyroid hormone (PTH). The study involved 70 children, 50 with INS and 20 healthy children. Patients with INS were divided into 4 groups depending on the number of relapses and applied therapy. Significantly higher concentrations of FGF-23 and Scl were found in all patient groups with INS compared to the control group, and increase in the concentrations of examined parameters depending on the number of NS relapses was showed. In patients from the group with numerous relapses, higher concentrations of FGF-23 and Scl in the relapse phase than those in the remission phase were found. We observed positive correlation in these proteins with parathyroid hormone. Positive correlation of FGF-23 and Scl in the examined group was noted. Children having relapsing INS treated with steroids have higher levels of Scl and FGF-23 that can indicate the bone metabolism disorders. The significance of these observations requires further research.

2019 ◽  
Vol 21 (4) ◽  
pp. 271-278
Author(s):  
Maciej Brzęczek ◽  
Lidia Hyla-Klekot ◽  
Franciszek Kokot ◽  
Marek Synder

Background. The multifactor aetiology of adolescent idiopathic scoliosis is commonly acknowledged. Both multivariate analyses of large study groups and the search for causes of adolescent idiopathic scoliosis and its progression in individual patients indicate that the aetiopathogenesis of this disorder is remarkably complex. The discovery of novel bone turnover markers, such as Klotho protein and FGF-23, means that their role in this condition also has to be considered. The aim of this paper is to evaluate the FGF-23 and Klotho protein concentration profiles as new contributors to the regulation of calcium and phosphate metabolism in children with adolescent idiopathic scoliosis and compare them with the values seen in healthy children. Material and methods. The study assessed a total of 70 children, including 35 children treated at the postural defects clinic of the Health Care Facility in Oleśno following a diagnosis of adolescent idiopathic scoliosis and 35 healthy children who constituted a control group. The levels of classic bone turnover markers, such as calcium and phosphorus concentration, alkaline phosphatase, 25-OH-D, and parathyroid hormone (PTH) activity, and of newly discovered contributors to calcium and phosphate metabolism regulation, namely Klotho protein and FGF-23, were determined in both groups. Results. There were statistically significant differences in the levels of basic parameters of calcium and phosphate metabolism between children with scoliosis and the control group, with scoliotic patients showing elevated calcium and 25-OH-D levels and reduced parathyroid hormone levels. Klotho protein levels in children with scoliosis were significantly lower than in the control group. Moreover, the scoliotic patients showed a marked trend towards higher FGF-23 levels as compared to the control group. Conclusions. 1. Adolescent idiopathic scoliosis is characterised by multi-level abnormalities of calcium and phosphate metabolism. 2. The increased FGF-23 levels and reduced Klotho protein concentrations found in serum samples collected from children with ado­lescent idiopathic scoliosis may suggest that these hormones play a role in the aetiopathogenesis of the disorder.


2021 ◽  
Vol 8 (2) ◽  
pp. 207
Author(s):  
Ozohu A. Aliyu ◽  
Shamsudeen Mohammed ◽  
Yakubu Abdullahi

Background: Nephrotic syndrome is a clinical condition caused by alteration of glomerular membrane permeability resulting in a net loss of protein, and vitamin D binding proteins in urine leading to hypoalbuminaemia and hypocalcaemia. A positive correlation between serum albumin and ionized calcium in childhood nephrotic syndrome has been described but the correlation between total serum calcium or corrected serum calcium and serum albumin has not been extensively described.Methods: This study was carried out at Dalhatu Araf Specialist Hospital, Lafia Nigeria. Fifteen children with idiopathic nephrotic syndrome were recruited consecutively as the cases, 15 age and gender matched healthy children were recruited as the controls. Total serum calcium and albumin was assayed in all these children. Corrected serum calcium was calculated for the cases. Tests of correlation was carried out to see if there was any relationship between corrected or total serum calcium and serum albumin.Results: The mean total serum calcium and serum corrected calcium levels in the cases was 2.04±0.34 mmol/l and 2.5 mmol/l respectively. The mean total serum calcium was 2.12±0.32 mmol/l for the controls. The mean serum albumin level was 14.7±4.1 g/l and 34.6±2.7 mmol/l for the cases and controls respectively. A negative and weak correlation was found between serum albumin and corrected serum calcium and a similar negative correlation between serum albumin and total serum calcium.Conclusions: The common reports of a positive correlation between serum ionized calcium and serum albumin cannot be applied to total or corrected serum calcium and serum albumin.


2019 ◽  
Author(s):  
Forough Saki ◽  
Seyed Reza Kassaee ◽  
Azita Salehifar Salehifar ◽  
gholamhossein Ranjbar omrani

Abstract Background:phosphate homeostasis is mediated through complex counter regulatory feed-back balance between parathyroid hormone, FGF-23 and 1,25(OH)2D. Both parathyroid hormone and FGF-23 regulate proximal tubular phosphate excretion through signaling on sodium- phosphate cotransporters II a and II c . However, the interaction between these hormones on phosphate excretion is not clearly understood. We performed the present study to evaluate whether the existence of sufficient parathyroid hormone is necessary for full phosphaturic function of FGF-23 or not. Methods:In this case-control study, 19 patients with hypoparathyroidism and their age- and gender-matched normal population were enrolled. Serum calcium, phosphate, alkaline phosphatase,parathyroid hormone, FGF-23, 25(OH)D, 1,25(OH)2D and Fractional excretion of phosphorous were assessed and compared between the two groups, using SPSS software. Results:The mean serum calcium and parathyroid hormone level was significantly lower in hypoparathyroid patients in comparison with the control group(P<0.001 and P<0.001, respectively). We found high serum level of phosphate and FGF-23 in hypoparathyroid patients compared to the control group (P<0.001 and P<0.001,respectively). However, there was no significant difference in Fractional excretion of phosphorous or 1,25OH2D level between the two groups. There was a positive correlation between serum FGF-23 and Fractional excretion of phosphorous just in the normal individuals (P <0.001, r = 0.79). Conclusions:Although the FGF-23 is a main regulator of urinary phosphate excretion but the existence of sufficient parathyroid hormone is necessary for the full phosphaturic effect of FGF-23.


2018 ◽  
Vol 47 (3) ◽  
pp. 164-170 ◽  
Author(s):  
Shoji Tsuji ◽  
Chikushi Suruda ◽  
Masaki Hashiyada ◽  
Takahisa Kimata ◽  
Sohsaku Yamanouchi ◽  
...  

Background: While the etiology of idiopathic nephrotic syndrome (idiopathic nephrotic syndrome [INS]; characterized by repeated relapses and comorbid allergic conditions) remains unknown, recent evidence suggests that dysfunction in regulatory T cells (Tregs) plays an important role in the development of INS as well as allergic diseases. We hypothesized that dysbiosis involving decreased butyric acid-producing gut microbiota leads to defective induction and differentiation of peripherally induced Tregs, resulting in INS relapse. Methods: Study subjects were 12 children with INS, 8 classified as relapsing (R group; median age: 3.0 years) and 4 as non-relapsing (NR group; median age: 4.3 years), and 11 healthy children (HC group; median age: 5.1 years) serving as normal controls. Measurement of microbiota was performed using 16S ribosomal RNA metagenomic analysis, and fecal butyric acid was measured using high performance liquid chromatography. Flow-cytometric analysis of Tregs and CD4-positive (CD4+) cells in peripheral blood was also performed. Results: Metagenomic analysis of gut microbiota using feces showed that the proportion of butyric acid-producing bacteria was significantly lower in R (median 6.36%) than HC (median 18.84%; p = 0.0013), but no different between NR (median 16.71%) and HC (p = 0.29). Fecal organic acid analysis revealed significantly lower butyric acid quantities in R than HC (medians: 0.48 vs. 0.99 mg/g, p = 0.042). Circulating Tregs as a proportion of CD4+ cells were decreased in 75% of R and NR. Conclusion: Pediatric relapsing INS patients show gut microbiota dysbiosis, characterized by a decreased proportion of butyric acid-producing bacteria and lower fecal butyric acid quantities, concomitant with reduced circulatory Tregs.


1987 ◽  
Author(s):  
T Gadelha-Parente ◽  
M Gouault-Heilmann ◽  
G Rostoker ◽  
M Levent ◽  
S Rafowicz ◽  
...  

25 consecutive patients (15M, 10F ; mean age 30 years) with nephrotic syndrome (NS) of different grade were studied. Control group consisted in 18 healthy adult volunteers. Total protein S antigen (TPS:Ag) and free protein S antigen (FPS:Ag) after precipitation of C4-BP-bound protein S by PEG 3-5 % final concentration were measured by Laurell's technique. PS:Ag was also searched in concentrated urine of 9 patients by ELISA method, more sensitive than the Laurell's technique. In the same plasma samples we measured C4-BP, Protein C Ag and AT III biological activity (all reagents from D.Stago). Serum albumin level, proteinuria, proteinuria selectivity index, triglycerides, cholesterol levels were recorded. TPS:Ag was found elevated in NS (1.30±0.3 U/ml) in comparison with control group (1.09±0.32 U/ml) and the difference was statistically significant (p<0.05). The mean values of FPS:Ag observed in patients and controls were not statistically different, but if we consider 95 % confidence limits (0.99-1-35 U/ml), 16 pts had normal or elevated FPS:Ag level, whereas 9 had decreased FPS:Ag level. A positive correlation was found between TPS:Ag and FPS:Ag in control group (r=0.66 ; p< 0.001) and in patients with NS (r=0.4l, p<0.05). C4-BP was significantly (p<0.01) increased in nephrotic patients ( 1.37 ± 0.36 U/ml) in comparison with control group (1.04±0.27 U/ml). A negative correlation was found between FPS:Ag and C4-BP levels in control group (r = −0.57, P< 0.01) but not in nephrotic patients. A positive correlation was found between FPS:Ag and albumin level and between FPS:Ag and cholesterol level. No correlation was found between TPS:Ag or FPS:Ag and proteinuria, proteinuria selectivity index, AT III and protein C levels. Traces of PS were found in urine (0. to 2.5 U/day) in 9 patients tested. 2/25 pts suffered thromboembolic events : one had a very low level of FPS:Ag in addition to a decreased level of AT III. The other one had normal FPS:Ag and AT III level but a borderline Protein C level. In conclusion. An acquired FPS:Ag deficiency was observed in 9/25 pts with NS despite an increased level of TPS:Ag. In this small series of patients the acquired FPS deficiency does not seem to be related either to an urinary loss of FPS or to an increased binding to C4-BP, as suggested by some authors.


2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Altynay Balmukhanova ◽  
Kairat Kabulbayev ◽  
Assiya Kanatbayeva ◽  
Harika Alpay ◽  
Aigul Balmukhanova ◽  
...  

Abstract Background and Aims Chronic kidney disease (CKD) is considered a global medical and public health issue. CKD takes a special place among non-infectious diseases because of its prevalence (6-20% according to different surveys and studies) and is associated with a poor life quality, complications and high risk of mortality. In recent years, there have been new biomarkers requiring more research in this area. One of these biomarkers is Fibroblast growth factor-23 (FGF-23) which is found as a bone derived hormone and might be a predictor of progression. However, the role of FGF-23 in CKD progression in children has not been adequately studied, especially on the early stages. Nowadays, the study of FGF-23 in children and the question of the clinical importance of this marker are relevant. Therefore, the aim of our study was to establish the role of FGF-23 in CKD progression in children. Method A prospective study was conducted on 73 children with different stages of CKD and 14 healthy individuals (control group) matched by age and gender. There were approximately equal numbers of patients in study groups. An average age was 9.61±1.05 years. Exclusion criteria: active inflammatory, bone, infectious, oncological, immunological diseases, taking steroids and vitamin D supplements. Laboratory measurements included all common clinical and biochemical indicators. Serum concentration of intact FGF-23 was assessed by using the ELISA method (Biomedica Medizinprodukte GmbH, Austria). Statistical analysis was conducted in MS Excel 2016 and SPSS 18.0. Results The normal range of FGF-23 for this kit was 0.1-1.5 pmol/l. The average value of FGF-23 in the control group was 0.69±0.12 pmol/l. Further studies in the groups with different stages of CKD revealed that FGF-23 concentration gradually rose in parallel with stages of CKD, and it reached the maximum on the last stage. It should be noticed that the level of FGF-23 concentration on the first stage of CKD was normal (0.73±0.14 pmol/l) and the comparison with healthy individuals revealed no significant differences. What is remarkable, despite the fact that the average value of the second stage patients was normal (1.36±0.2 pmol/l), there was a statistically significant difference with the control group (p=0.008). The levels of FGF-23 on the next stages were 2.52±0.52 pmol/l, 5.42±1.61 pmol/l, and 12.16±1.55 pmol/l, respectively. The differences were considerable and proved by statistical analysis (p&lt;0.01). Conclusion Our study showed that there is an upward trend of FGF-23 as CKD progresses from early to advanced stages. The results on the second and third stages indicate that FGF-23 should be considered as one of early biomarkers of CKD progression in children. Thus, there is a need for more studies in this area.


Author(s):  
Fadhil Jawad Al-Tu'ma ◽  
Anaam Hato Kadhim ◽  
Anaam Hato Kadhim ◽  
Saif Sami Al-Mudhaffar

Coronary artery disease (CAD) is a clinical manifestation resulting from a narrowing of epicardial coronary arteries that supply blood and oxygen to the heart. Coronary artery disease is mostcommonlydue to atherosclerotic occlusion of the coronary arteries.Fibroblast growth factor 23 (FGF23) is a circulating peptide hormone secreted by bone cells,regulating phosphate and vitamin D metabolism. Several recent observational studies reported an independent association of circulating FGF23 with several cardiovascular disease (CVD) risk factors including left ventricular hypertrophy and vascular dysfunction,CVD progression and incident clinical CVD eventsand mortality.Apolipoprotein A1 (ApoA1) is the primary protein associated with high-density lipoprotein (HDL) particles,and plays a central role in reverse cholesterol transport. HDL cholesterol (HDL-C) and ApoA1 concentrations are inverlassely related to the risk for coronary artery disease. To find the role of fibroblast growth factor-23 in coronary artery disease and its associationwith Apolipoprotein-A1.This ccross –sectionalstudyincluded 42 elective patients attending the cardiology unit and the results of those patients were compared with 40 healthy control group. Blood samples were obtained for measurements of (FGF-23,troponin I,Apo-A1,total creatine kinase activity,urea,creatinine and lipid profile).The obtained results showed that there was a significant difference in serum FGF-23 in coronary artery disease (367.52 ± 128.52 pg/ml) as compared with the control (165.41 ± 53.65 pg/ml) (p< 0.05). There was a significant differences in Apo-A1 in coronary artery disease (2.03±0.90 mg/ml) as compared with the control (1.49 ± 0.25 mg/ml) (P = 0.014).There was a significant difference in age between CAD (58.66±8.85) and control group (51.125 ± 11.71) (P<0.005).There was a significant difference in TG where control (99.50 ± 21.59) differ from CAD (142.05 ± 66.24) (P = 0.006).According to the results that were shown in the tables, we can be conclude that higher levels of FGF23 and Apo-A1 may be associated with complications and mortality of CAD beside its associating with atherosclerosis in the Iraqi patients.


2020 ◽  
Vol 49 ◽  
Author(s):  
K. M. Koreshkova ◽  
Z. R. Khismatullina

Relevance: Psoriatic arthritis (PA) is a severe complication of psoriasis, leading to progressive damage to the musculoskeletal system, a decrease in the quality of life and early disability. CASPAR criteria, widely used for PA diagnosis, are highly sensitive and specific. However, some patients with psoriasis score ≥ 3 with CASPAR criteria without an established PA diagnosis. At present, there is a search for PA biomarkers, which could mirror the stages of pathogenesis of joint and enthesis destruction in this disease.Aim: To identify the most significant changes in biochemical parameters in patients with PA, that would be pathophysiologically associated with the disease.Materials and methods: We performed an open label comparative parallel group study in 60 patients with PA and 40 patients with psoriasis without PA. Clinical assessments included filling in the questionnaires, past history, dermatologist consultation, severity of psoriasis by PASI, and PA activity. Clinical chemistry examination included the levels of antibodies to citrullinated peptide, erythrocyte sedimentation rate, C-reactive protein (CRP), human leukocyte antigen HLA B27, immunoglobulins A, M, and G, complement system components C3, C4, circulating immune complexes (CIC), as well as bone metabolism parameters (calcium, phosphorus, magnesium, seromucoid, alkaline phosphatase (AP), osteocalcin, parathyroid hormone, vitamin D, matrix metalloproteinases MMP-1, MMP-3, MMP-8, and cartilage oligomeric matrix protein (СОМР).Results: Psoriasis was diagnosed in 86.6% (n = 52) of the patients with PA. Family history of psoriasis was confirmed in 55.0% (n = 22) of the patients with psoriasis without PA and in 60.0% (n = 36) of the patients with PA (p = 0.681). Compared to the patients with psoriasis without PA, the patients with PA had higher prevalence of psoriatic onychodystrophy (71.6%, n = 43, vs. 35.0%, n = 14, p = 0.0004), dactylitis (28.3%, n = 17, vs. 5.0%, n = 2, p = 0.004), extra-articular bone proliferation signs (26.6%, n = 16, vs. 5.0%, n = 2, p = 0.006). In the patients with PA, compared to those without PA, there was a significant increase in CRP levels (27.4 vs. 9.5 mg/l, p = 0.002), more than 2-fold increase in IgM and IgG (IgM, 2.35 vs. 1.2 g/l, p = 0.023; IgG, 17.7 vs. 8.45 g/l, p < 0.0001), and CIC (89.3 vs. 29.5 mU/ml, p = 0.0003). Serum phosphorus and magnesium levels in the patients with PA were lower than in the psoriasis patients without PA (phosphorus 0.8 vs. 1.6 mmol/l, respectively, p = 0.045, magnesium 0.5 vs. 1.0 mmol/l, respectively, p = 0.001), with somewhat higher parathyroid hormone levels (67.3 vs. 25.1 ng/ml, respectively, p = 0.013). Osteocalcin levels in the PA patients were by 37.3% lower than in the patients with psoriasis without PA (17.57 vs. 24.13 ng/ml, respectively, p = 0.004). MMP-1 levels in the PA group were 12.3-fold higher than in the non-PA group (37.68 vs. 3.05 ng/ml, respectively, p < 0.0001), and MMP-3 levels were 3.7-fold higher (42.35 vs. 11.36 ng/ml, respectively, p = 0.022). In the patients with PA, AP levels were 2.52-fold higher than in the control group (150.2 vs. 59.5 U/ml, respectively, p = 0.007), and COMP levels were 2.08-fold higher (415.2 vs. 199.5 ng/ml, respectively, p = 0.006).Conclusion: The patients with PA have higher serum CRP, IgM, IgG, CIC, MMP-1, MMP-3, AP, and COMP levels and lower osteocalcin, phosphorus, and magnesium concentrations, than the patients with psoriasis. These parameters are not PA-specific; however, the search for the most sensitive biomarkers of the systemic immune response and bone remodeling seems to be a promising area of research, since identification of such markers would allow for timely prediction and detection of PA in patients with psoriasis.


2021 ◽  
Vol 64 (2) ◽  
pp. 37-41
Author(s):  
Angela Ciuntu ◽  

Background: Cytokines are functional class of tiny proteins and glycoprotein and fundamentally they are monomers that function as soluble mediators in an autocrine or paracrine manner. Cytokines are produced by a number of cell types, predominantly leukocytes, and their targets implicate both immune and non-immune cells. Material and methods: This study was performed on 75 children with glomerulonephritis (GN), aged from 2 up to 17 years. There were 20 children with steroid-sensitive nephrotic syndrome (SSNS), 15 children with steroid-resistant nephrotic syndrome (SRNS), 20 children with chronic glomerulonephritis (CGN) nephrotic form and 20 children with CGN mixed form. This study was performed on patients experiencing disease relapse and clinical remission. The control group consisted of 20 healthy children. Results: The results of this study demonstrated increased levels of cell signaling molecules (IL-8, TNF-α, MCP-1, MIP-1α) in the urine during clinical manifestations, valuable result due to their major role in the immunopathogenic mechanism of proteinuria in nephrotic syndrome. Conclusions: Determination of urinary concentrations of cellular signaling molecules may be useful as a predictive non-invasive method for estimating disease activity, monitoring disease progression, differentiating steroid-sensitive nephrotic syndrome from steroid-resistant nephrotic syndrome, and assessing the effectiveness of treatment in children with different variants of GN


2018 ◽  
Vol 58 (2) ◽  
pp. 84-9
Author(s):  
Partini Pudjiastuti Trihono ◽  
Deasy Grafianti ◽  
Irawan Mangunatmadja ◽  
Mulya Rahma Karyanti

Background Long-term treatment with antiepileptic drugs such as valproic acid (VPA) and carbamazepine (CBZ) may disrupt renal tubular function. Urinary N-acetyl-beta-D-glucosaminidase (NAG) may reflect tubular function and may be useful in detecting early-stage tubular injury. To date, no study has investigated the toxic effect of VPA and CBZ on renal tubules using urinary NAG in Indonesian children. Objectives To determine the toxicity of long-term VPA and/or CBZ treatment on renal tubules in children with epilepsy by measuring urinary NAG index (iNAG). Methods This cross-sectional study was conducted from January to March 2015 at Cipto Mangunkusumo Hospital and Anakku Clinic Pondok Pinang, Jakarta. We included children aged 3 to 16 years with epilepsy on VPA (n=36), CBZ (n=14), or VPA-CBZ combination (n=14) therapy. We measured urinary levels of creatinine and NAG. The urinary NAG reference value was obtained from age-matched healthy controls (n=30). To eliminate diurnal variations in NAG, iNAG was calculated by dividing urinary NAG by urinary creatinine. A urinary iNAG of more than two standard deviations above the mean for healthy children was considered elevated. Results Mean urinary iNAG values for the control, VPA, CBZ, and combination groups were 3.01, 5.9, 4.07, and 6.9 U/g, respectively. All treated groups had higher mean urinary iNAG values compared to the control group. Urinary iNAG was increased in 11/36 children on VPA, 2/14 children on CBZ, and 9/14 children on combination therapy. Conclusion Long-term VPA use may impair renal tubular function, as shown by the increased urinary iNAG. Combination therapy increases damage in the renal tubules.


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