Calcium-phosphorus Metabolism Research Articles

Etiopathogenetic features of bone metabolism in patients with diabetes mellitus and Charcot foot

Diabetic neuropathy is one of the most common diabetes mellitus complications associated with mediocalcinosis of the lower extremities, a significant decrease in feet bone mineral density, and a high incidence of cardiovascular disease. In most cases, calcium-phosphorus metabolism changes occur in patients with diabetic neuroarthropathy, or Charcot foot, when we can observe feet local osteoporosis, which in 90% of cases associated with a vessel’s calcification of the lower extremities in the majority of diabetes population. A large number of studies presented literature have demonstrated that patients with Charcot foot can have accelerated bone metabolism and increased bone resorption. Patients with Charcot foot often have crucial abnormalities in the calcium-phosphorus parameters, bone metabolism, and levels of vitamin D and its metabolites. In addition, the duration of diabetes mellitus, the degree of its compensation widely affects the development of its micro- and macrovascular complications, which could also accelerate the development of mineral and bone disorders in these types of patients. Multifactorial pathogenesis of these disorders complicates the management of patients with a long and complicated course of diabetes mellitus. This review discusses the peculiarities of vitamin D metabolism, the importance of timely diagnosis in phosphorus-calcium disorders, and the specifics of therapy in these patients. Special attention is paid to the timely diagnosis of the Charcot’s foots acute stage based on the bone marrow edema by MRI evaluation and the possibility of reducing the immobilization period.

Calcium-Phosphorus Metabolism in Females with Autoimmune Thyroiditis and Hypothyroidism

Thyroid dysfunction is frequently associated with disturbances of calcium and phosphorus homeostasis. Previous studies on bone and mineral metabolism in women with autoimmune thyroiditis (AIT) and hypothyroidism have conflicting results. The aim of the present work was to study the parameters of calcium-phosphorus metabolism in women with newly diagnosed autoimmune hypothyroidism and to compare them with those of the control group of healthy women. The study included 64 women with newly diagnosed autoimmune hypothyroidism. A comparison was made with the data of 75 age-, BMI- and menopausal state-matched healthy women. FT3, FT4, TSH, TPO-Ab, TG-Ab, total and ionized serum calcium, inorganic phosphate, magnesium, parathyroid hormone (PTH) and 25(OH) vitamin D were studied. Total and ionized calcium were lower in hypothyroid women in the absence of statistically significant difference compared to the controls. Intergroup analysis revealed no differences in serum phosphorus and 25(OH)D levels. Serum magnesium and PTH were significantly higher in hypothyroid group. These results coincide with some of the studies that examine the parameters of bone and mineral metabolism in hypothyroidism. Bone turnover is suppressed due to impaired mobilization of calcium from the bone, leading to decreased serum calcium levels and elevated PTH. We found a significant effect of thyroid hormones on magnesium homeostasis. The study did not find differences in vitamin D status between the groups. The observed inverse correlation between 25(OH)D and TgAb supports the concept of pathogenic relationship between vitamin D and the development of AIT.

ДИФФЕРЕНЦИАЛЬНАЯ ДИАГНОСТИКА БОЛЕЗНИ БЛАУНТА: КЛИНИЧЕСКОЕ НАБЛЮДЕНИЕ

Lower extremities deformation is observed quite often in infants. One of the Blount's disease diagnosis features is the difficulty of its differential diagnosis of when excluded from other conditions such as rickets, rickets-like diseases and physiological curvature of the lower extremities in infants. Article represents the main diagnostic criteria for the abovementioned diseases. A clinical case of a patient with Blount's disease who had deviations in calcium-phosphorus metabolism that in their turn are uncommon for this pathology is described. The entire set of clinical and laboratory signs analysis was carried out in details, which then made it possible to carry out a differential diagnosis and exclude hereditary forms of rickets, primarily hypophosphatemic rickets as the reason for pronounced varus deformity of the legs in a 2.5 y/o pediatric patient. The tactics for further treatment by a specialized practitioner had been determined as well.

Measurement of Vitamin D Level among Covid-19 Patients and its Correlation with Severity of the Disease

Abstract Background Coronavirus disease 2019 (covid-19) is defined as illness caused by a novel coronavirus now called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which was first identified among an outbreak of respiratory illness cases in Wuhan City, China. Vitamin D is known to play a key role in the maintenance of bone health and calcium–phosphorus metabolism, yet many other functions of this vitamin have been recently postulated, such as modulation of the immune response in both infectious and autoimmune diseases. Different studies showed that severity of covid-19 infection is directly related to vitamin D level. Methods This is an observational cross-sectional study, which includes 80 COVID-19 patients, and admitted in the ward and ICU of EL Medany Hospital, EL Demerdash and EL Obour specialized hospital. All patients had positive PCR for COVID-19. Chest CT without contrast was done for all patients and categorized according to CORAD staging. Serum vitamin D level was measured, besides laboratory inflammatory markers (CRP, ferritin, d-dimer), kidney and liver function tests, and complete blood picture. Results Our study included 80 patients; 33 males and 47 females with mean age of (51±10.5 years). Measured Vitamin D level range was (10±9 ng/mL). It was found that male patients had higher level of serum vitamin D (12.6±8.6 ng/mL) than female patients (11.5±9.5 ng/mL) but with no statistically significant difference. The commonest presentations were sore throat (97.5%), and fever (93.75%). COVID-19 patients presenting with cough and fever had highly significantly lower levels of vitamin D than patients not presenting by these symptoms (P-value 0.006, 0.032) respectively. In the current study, patients with CORAD 5 in chest CT had the lowest vitamin D level (9.6±7.8 ng/mL), compared to patients with CORAD 3 (13.6±9.7 ng/mL), and CORAD 4 (11.8 ±8.8 ng/mL). According to the correlation analysis, a decrease in vitamin D levels was associated with more severe COVID-19 cases, with significantly higher blood levels of inflammatory markers CRP and ferritin (P-value 0.02, 0.01). No correlation was found between vitamin D levels and hemoglobin level, white cell count, platelet count, or D-Dimer. Conclusion Our findings suggest that the COVID-19-positive individuals with lower vitamin D levels, had significantly higher blood levels of inflammatory markers (Ferritin and CRP), and increased frequencies of ground-glass opacity appearance in chest CT scans. Accordingly, vitamin D deficiency may be a marker of poor prognosis in COVID-19 patients.

Features of Bone Mineral Density, Calcium-Phosphorus Metabolism and Bone Remodeling in Patients with Systemic Lupus Erythematosus

Introduction. Systemic lupus erythematosus (SLE) is a complex autoimmune disease with variable clinical manifestations associated with multiple autoantibodies formation and deposition of immune complexes, and other immune processes. Despite significant advances in treatment, the disease remains disabling, in particular, due to increased bone fragility and low-energy fractures. The study of bone remodeling in patients with SLE should help to improve the therapy and quality of their treatment. The aim of the study. To investigate the features of bone mineral density, calcium-phosphorus metabolism and bone remodeling in patients with systemic lupus erythematosus. Materials and methods. The study involved 123 women with SLE aged 21-51 years. The comparison group (CG) consisted of 25 women without SLE in premenopausal status of the appropriate age. The control group included 25 practically healthy women. In order to study bone mineral density (BMD), dual-energy X-ray densitometry (DXA) of the lumbar spine was performed using a dual-energy X-ray absorptiometer. For the study of calcium-phosphorus metabolism (CPM), total calcium (Ca), ionized Ca, phosphorus (P) in blood and Ca, P, creatinine in daily urine, as well as parathyroid hormone (PTH) and 25-hydroxyvitamin D in serum were determined. Markers of bone remodeling (osteocalcin, procollagen type 1 amino-terminal propeptide (P1NP) and isomerized C-terminal telopeptide (β-crosslaps) in serum were measured. To achieve the stated goal, the first step included the determination of bone damage prevalence in patients with the diagnosed SLE; the second step was directed towards the characterization the particular bone condition in patients with SLE based on the results of BMD, CPM indices and markers of bone remodeling assessment. Results and discussion. According to the results of DXA of the lumbar spine, 88 (71.54 %) women of the SG and only 8 (32.00 %) women of the CG had a decrease in BMD (p < 0.001). According to the mean values, the studied CPM indices of the SG patients, CG and control group wemen exposed no significant differences. Similarly, no significant differences were detected in the mean values of urinary phosphorus and in between blood PTH values in SG, CG, and control. The level of 25-hydroxyvitamin D was significantly lower in SG (15.14 ± 0.80 ng/ml) than in CG (19.62 ± 0.46 ng/ml) and control (22.38 ± 1.34 ng/ml) p < 0.05. The mean value of osteocalcin in woman with SLE was significantly lower than in CG and control (11.81 ± 0.49 ng/ml versus 18.61 ± 0.75 ng/ml and 19.28 ± 1.88, p < 0.001). No significant difference were detected in between the mean values of P1NP in SG, CG and control. The mean values of β-cross laps were significantly higher in patients with SLE (0.51 ± 0.02 ng/ml) compared to GC (0.26 ± 0.02 ng/ml) and control (0.28 ± 0.02 ng/ml), p < 0.001. Conclusions. Bone mineral density, calcium-phosphorus metabolism and bone remodeling in patients with systemic lupus erythematosus have peculiarities as follows: a significant decrease in bone mass in 71.54 % of patients, namely 18, 70 % - grade I osteopenia, 21.14 % - grade II osteopenia, 14.63 % - grade III osteopenia; 17.07 % - osteoporosis, increased calcium excretion, vitamin D deficiency, decreased osteoblastic and enhansed osteoclastic functions.

Effect of high-flux hemodialysis plus compound-α Ketoacid tablets under humanistic care on calcium-phosphorus metabolism in uremia patients.

Uremia (UR) is a terminal renal failure manifestation with a very high risk of death, high-flux hemodialysis (HFHD) is currently the most common treatment for UR in clinical practice. In this study, we analysed the therapeutic efficacy of HFHD plus Compound-α Ketoacid Tablets for UR under humanistic care. Firstly, we randomised 100 patients with UR into a research group (RG) for HFHD plus Compound-α Ketoacid Tablets therapy and a control group (CG) for HFHD treatment, with both therapies implemented under humanistic care. By way of comparison, we found that the study group had significantly better renal function after treatment and they had a lower inflammatory response. Also, the study group showed lower calcium and phosphorus metabolism and better immune function. Based on these results, we believe that HFHD + Compound-α Ketoacid Tablets under humanistic care have high clinical value.

#1552 The role of osteocytes in bone remodeling: comparison between biopsies from patients with osteitis fibrosa and mixed uremic osteodystrophy disease

Abstract Background and Aims Osteocytes represent about 95% of bone cells. They are located in mineralized bone tissue and connect with each other, with osteoblasts, osteoclasts, blood vessels and bone marrow cells. These cells express several proteins that regulate phosphorus-calcium metabolism and bone remodeling. Disorders of mineral metabolism resulting from chronic kidney disease – mineral bone disorder (CKD-MBD) alter tissue function leading to histological changes known as renal osteodystrophy (ROD). ROD is classified: in high turnover – osteitis fibrosa (OF) and mixed uremic osteodystrophy (MUO) and low turnover – adynamic bone disease and osteomalacia. The participation of osteocytes proteins in ROD pathogenesis is not fully explained. The aim of this study was to evaluate the expression of osteocytic proteins in bone biopsies from patients with OF and MUO and analyze clinical, biochemical and bone histomorphometric results. Method We evaluated patients with CKD on hemodialysis, who underwent bone biopsy to elucidate the diagnosis of ROD. Static and dynamic parameters by histomorphometry, including quantification of osteocytes, and the expression of proteins by immunohistochemistry (Sclerostin; Nuclear factor Kappa B ligand – RANKL; Osteoprotegerin – OPG; Dickkopf-related protein 1 - DKK1; Fibroblast growth factor 23 - FGF23; Dentin matrix protein 1 - DMP1; Matrix extracellular phosphoglycoprotein – MEPE; Phosphate regulatory gene with homologies to endopeptidases on the X chromosome – PHEX; podoplanin - E11; and CD44). Results We included 47 patients (24 with OF and 23 with MUO). Table 1 describes the results from the comparison between both groups. Patients with MUO were older and had lower serum P levels compared to patients with OF. Histomorphometric results showed that the structural parameter trabecular number was greater in patients with OF. The formation parameters, as osteoid volume, thickness and surface were greater in patients with MUO. Regarding mineralization, these patients also have lower bone formation rate, and mineralizing surface and a longer mineralization lag time. The expression of osteocytic proteins in both groups showed that DMP-1 was approximately 50% lower, near to statistical significance (p = 0.07) and RANKL was 23% lower in patients with MUO. In Table 2 are described the association found between proteins and histomorphometric parameters. The majority of the proteins involved in bone remodeling are negatively associated with histomorphometric parameters. Conclusion The clinical symptoms of CKD-BMD in patients with OF and MD are similar, and, except for serum P levels, other biochemical parameters did not contribute to differentiate Of and MUO. Bone biopsy, despite being an invasive procedure, revealed differences between the two pathologies, which could better guide clinical treatment, such as, vitamin D supplementation and VD analogs in patients with MUO who present an increase in osteoid parameters, which could improve bone mineralization. Regarding the expression of proteins in osteocytes, we found few differences between the two groups. However, several associations were observed between the expression of these proteins and structural, formation, reabsorption and mineralization parameters in high turnover bone disease.

Molecular Insights into the Effects of F16L and F19L Substitutions on the Conformation and Aggregation Dynamics of Human Calcitonin.

Human calcitonin (hCT) regulates calcium-phosphorus metabolism, but its amyloid aggregation disrupts physiological activity, increases thyroid carcinoma risk, and hampers its clinical use for bone-related diseases like osteoporosis and Paget's disease. Improving hCT with targeted modifications to mitigate amyloid formation while maintaining its function holds promise as a strategy. Understanding how each residue in hCT's amyloidogenic core affects its structure and aggregation dynamics is crucial for designing effective analogues. Mutants F16L-hCT and F19L-hCT, where Phe residues in the core are replaced with Leu as in nonamyloidogenic salmon calcitonin, showed different aggregation kinetics. However, the molecular effects of these substitutions in hCT are still unclear. Here, we systematically investigated the folding and self-assembly conformational dynamics of hCT, F16L-hCT, and F19L-hCT through multiple long-time scale independent atomistic discrete molecular dynamics (DMD) simulations. Our results indicated that the hCT monomer primarily assumed unstructured conformations with dynamic helices around residues 4-12 and 14-21. During self-assembly, the amyloidogenic core of hCT14-21 converted from dynamic helices to β-sheets. However, substituting F16L did not induce significant conformational changes, as F16L-hCT exhibited characteristics similar to those of wild-type hCT in both monomeric and oligomeric states. In contrast, F19L-hCT exhibited substantially more helices and fewer β-sheets than did hCT, irrespective of their monomers or oligomers. The substitution of F19L significantly enhanced the stability of the helical conformation for hCT14-21, thereby suppressing the helix-to-β-sheet conformational conversion. Overall, our findings elucidate the molecular mechanisms underlying hCT aggregation and the effects of F16L and F19L substitutions on the conformational dynamics of hCT, highlighting the critical role of F19 as an important target in the design of amyloid-resistant hCT analogs for future clinical applications.

Innovative Treatments to Counteract Endothelial Dysfunction in Chronic Kidney Disease Patients.

In chronic kidney disease (CKD) patients, several risk factors contribute to the development of endothelial dysfunction (ED), which can be described as an alteration in the cell structure or in the function of the endothelium. Among the well-known CKD-related risk factors capable of altering the production of endothelium-derived relaxing factors, we include asymmetric dimethylarginine increase, reduced dimethylarginine dimethylamine hydrolase enzyme activity, low-grade chronic systemic inflammation, hyperhomocysteinemia, oxidative stress, insulin resistance, alteration of calcium phosphorus metabolism, and early aging. In this review, we also examined the most important techniques useful for studying ED in humans, which are divided into indirect and direct methods. The direct study of coronary endothelial function is considered the gold standard technique to evaluate if ED is present. In addition to the discussion of the main pharmacological treatments useful to counteract ED in CKD patients (namely sodium-glucose cotransporter 2 inhibitors and mineralocorticoid receptor antagonist), we elucidate innovative non-pharmacological treatments that are successful in accompanying the pharmacological ones. Among them, the most important are the consumption of extra virgin olive oil with high intake of minor polar compounds, adherence to a plant-dominant, low-protein diet (LPD), an adaptive physical activity program and, finally, ketoanalogue administration in combination with the LPD or the very low-protein diet.

Benign paroxysmal positional vertigo: case developed with hyperparathyreoidism and vitamin D deficiency

The most common cause of spinning vertigo is benign paroxysmal positional vertigo (BPPV). Most cases are related to idiopathic BPPV, which pathogenesis is still not fully understood. In this manuscript the clinical case of recurrent benign paroxysmal positional vertigo is depicted. BPPV in this case was occurred primary in menopausal period. A clinical feature of this case is its combination not only with vitamin D deficiency and postmenopausal osteopenia (confirmed according to osteodensitometry), but also with secondary hyperparathyroidism, laboratory confirmed. The literature has accumulated data to link the development and recurrence of BPPV with vitamin D deficiency and osteoporosis, but few comprehensive studies of all crucial indicators of calcium-phosphorus metabolism in these patients have been published. Meanwhile, according to the author, a comprehensive endocrinological study of calcium-phosphorus metabolism in a patient with newly diagnosed BPPV can help optimize therapy for this category of patients.

Current approaches to the management of vitamin D deficiency and insufficiency in adults

The issue of optimal management of vitamin D deficiency and insufficiency is very topical. The role of vitamin D in the regulation of not only phosphorus-calcium metabolism, but also the relationship between its deficiency status and the risk of developing various diseases, including autoimmune, metabolic, oncological, cardiovascular, etc., has been well studied. Studies have shown that vitamin D deficiency and insufficiency are detected in 84.3% of examined population aged 18 to 50 years in Russia as a whole. According to the results of studies, the level of consumption of vitamin D foods in our country does not ensure adequate vitamin D intake, and the only effective method for managing its deficiency and maintaining 25(OH)D concentrations at the proper level may be supplemental vitamin D intake in the form of drugs or food additives. Given the importance of maintaining adequate vitamin D levels and high prevalence rates of vitamin D deficiency and insufficiency in people of different ages and genders in various geographical regions of our country, there is a growing interest in options for timely and adequate therapy. Domestic experts have developed various therapeutic options for the management of vitamin D deficiency and insufficiency. A single dose of 300,000 IU of oral cholecalciferol once weekly, which proved to be effective and safe for managing vitamin D deficiency in adults is the best option from the perspective of medication adherence and patient convenience. Presently, the first high-dose drug, a matrix tablet containing 50,000 IU colecalciferol, has been granted a marketing authorization in Russia. The drug is indicated for the treatment of vitamin D deficiency and insufficiency.

Association between preoperative cholecalciferol therapy and hypocalcemia after parathyroidectomy in patients with primary hyperparathyroidism

Primary hyperparathyroidism (PHPT) is a endocrine disorder characterized by excessive secretion of parathyroid hormone (PTH) from parathyroid gland tumors. Parathyroidectomy (PTE) is the main treatment for PHPT, but it can lead to hypocalcemia in up to 46% of cases. Hypocalcemia is associated with seizures and life-threatening cardiac arrhythmias, and vitamin D deficiency can exacerbate PHPT severity and contribute to «hungry bones syndrome,» resulting in severe and persistent postoperative hypocalcemia. To evaluate the association and determine the strength of the relationship between preoperative cholecalciferol therapy and the occurrence of hypocalcemia within 1-3 days after PTE in patients with PHPT. The study was conducted at the Endocrinology Research Centre, during the periods of 1993-2010 and 2017-2020. The inclusion criteria consisted of patients diagnosed with PHPT who required PTE, had a serum 25-hydroxyvitamin D (25(OH)D) level below 20 ng/mL, and a serum total calcium level below 3 mmol/L. The exclusion criterion was the use of medications that affect calcium-phosphorus metabolism, including cinacalcet, denosumab, or bisphosphonates, either as monotherapy or as part of combination therapy. There were 117 patients, including 110 (94%) females and 7 (6%) males. The median age and interquartile range were 58 [49; 65] years. Among the participants, 21 (18%) received cholecalciferol supplementation for a duration of 2 weeks to 2 months prior to PTE, aiming to address vitamin D deficiency. The remaining 96 (82%) participants did not receive -cholecalciferol supplementation. Both groups, i.e., participants receiving cholecalciferol and those who did not, were similar in terms of anthropometric factors (sex and age at the time of surgery), preoperative clinical characteristics (BMD decrease), and laboratory parameters (PTH, total calcium, phosphorus, ALP, OC, CTX-1, and 25(OH)D levels). The occurrence of postoperative hypocalcemia was significantly lower in participants who received cholecalciferol supplementation (10% vs. 63%, p<0,001, FET2). Cholecalciferol intake showed a negative association with hypocalcemia development (RR=0,15, 95% CI (0,03; 0,51)). Preoperative cholecalciferol supplementation for 2 weeks to 2 months before PTE reduces the risk of postoperative hypocalcemia in patients with PHPT by 2-33 times.

Bone health in children with primary hyperoxaluria type 1 following liver and kidney transplantation.

Primary hyperoxaluria type 1 is characterized by hepatic oxalate overproduction, leading to nephrocalcinosis, kidney stones, kidney failure and systemic oxalosis, including oxalate osteopathy. Combined liver-kidney transplantation (CLKT) and kidney after liver transplantation (KALT) were established therapeutic options to stop the devastating consequences of oxalate bone disease. We describe a retrospective cohort of 10 children with PH1who were referred to our hospital from different countries for combined transplantation. Demographic and clinical data were collected and symptoms of bone disease, conventional radiological examinations, plasma oxalate levels and other determinants of calcium-phosphate metabolism were compared pre and post transplantation. Ten patients (7 male, median age 5.8 years, median follow-up time 8.1 years) were included in this study. Seven patients were diagnosed with infantile oxalosis and 9 patients received an intensified dialysis regime prior to transplantation. In one patient the transplanted kidney never achieved primary function and the boy remained on HD. All other patients remained without graft failure and retained stable kidney and liver function. Prior to transplantation, seven patients suffered from severe skeletal pain and three children presented with 1-3 series of pathological fractures. Pathological fractures did no longer occur in children who underwent successful CLKT or KALT. Plasma oxalate levels dropped within 6 months following Tx. Determinants of calcium-phosphorus metabolism did not differ significantly in comparison to other HD children. Seven of ten children showed a restricted growth at the time of transplantation and presented a moderate catch-up-growth at the time of last follow-up. Patients with PH1 suffer from severe consequences of a disturbed bone metabolism. However, bone health and growth can partially improve following CLKT/KALT.

Uraemia with imbalanced calcium phosphorus metabolism on [68Ga]Ga-FAPI versus [18F]F-FDGPET/CT.

Uraemia with imbalanced calcium phosphorus metabolism on [68Ga]Ga-FAPI versus [18F]F-FDGPET/CT.

Secondary hyperparathyroidity in patients with progressive chronic kidney disease

In patients with end-stage chronic kidney failure, there are a number of disorders that cause bone damage. In particular, secondary hyperparathyroidism (SHPT) is related to chronic kidney failure, a calcium-phosphorus metabolism disorder that causes bone disorder. Secondary HPT occurs when parathyroid hormone(PTH) is continuously produced in response to chronically low serum calcium levels, commonly seen in patients with progressive chronic kidney disease. In this article we present a case of secondary HPT causing facial and thoracic bone changes. Key words: end-stage chronic kidney failure, chronic kidney, secondary hyperparathyroidism (SHPT).

Calcium-phosphorus metabolism and assisted reproductive technologies: intersection points

Calcium-phosphorus metabolism and assisted reproductive technologies: intersection points

Hiperaldosteronismo e hiperparatiroidismo. Una amistad inquietante

Classically, aldosterone actions are associated with the stability of the effective circulating volume and with blood pressure control, while parathormone actions are linked to bone mineral metabolism, calcium, and phosphate homeostasis. Nevertheless, the relationship between these two hormonal axes surpasses these areas. A bidirectional interrelation between calcium-phosphorus metabolism and blood pressure control can lead to alterations in both. This can have significant implications for the evolution and treatment of patients. To illustrate this relationship, we present two clinical cases that demonstrate the pathophysiology involved.

МАТЕМАТИЧЕСКАЯ МОДЕЛЬ ДЛЯ ПРОГНОЗИРОВАНИЯ СНИЖЕНИЯ РАСЧЕТНОЙ СКОРОСТИ КЛУБОЧКОВОЙ ФИЛЬТРАЦИИ ЧЕРЕЗ 12 МЕСЯЦЕВ ПОСЛЕ ПАРАТИРЕОИДЭКТОМИИ У ПАЦИЕНТОВ С ПЕРВИЧНЫМ ГИПЕРПАРАТИРЕОЗОМ

Background. Primary hyperparathyroidism (PHPT) is an endocrine disease characterized by excessive production of parathyroid hormone (PTH) and elevated or high-normal blood calcium levels caused by primary pathology of the parathyroid glands. The "classic" complication of PHPT is a decrease in the kidneys filtration function. Parathyroidectomy (PTE) reduces the risks of further deterioration in filtration function; however, in some cases, this is not achieved. Aim. To develop a mathematical model to predict the decline in estimated glomerular filtration rate (eGFR) 12 months after PTE in patients with PHPT, and implement it as a software. Methods. Retrospective study included 140 patients with PHPT who underwent PTE in 1993–2010 and 2018–2020 at the National Medical Research Center of Endocrinology. Analyzed variables included sex, age, indicators of calciumphosphorus, purine, lipid, and carbohydrate metabolism, presence of PHPT complications, treatment for PHPT, histological examination of removed parathyroid tissue, development of postoperative hypocalcemia and transient hypoparathyroidism, therapy for postoperative hypocalcemia. The random forest method was used to build the mathematical model. Results. To predict the decline in eGFR, a model using 24 predictors was built: sex, age, body mass index, PTH, ionized calcium, alkaline phosphatase, phosphorus, urea, eGFR, total cholesterol, diastolic blood pressure, SD(T-score)<-2.5/ SD(Z-score)<-2.0, CKD, duration of nephrolithiasis, use of angiotensin II receptor blockers and angiotensin-converting enzyme inhibitors, preoperative use of cholecalciferol and cinacalcet, parathyroid hyperplasia/adenoma, postoperative hypocalcemia, dose of alfacalcidol and calcium supplements, postoperative use of cholecalciferol. The resulting model (http://194.87.111.169/cfr) predicts a decline in eGFR in patients with PHPT after PTE with a probability of 56.8–86.3% and excludes – with a probability of 85.6–97.7%. Conclusion. A mathematical model to predict the decline in eGFR 12 months after PTE in patients with PHPT was developed, with an overall accuracy of 88%, 95% CI (79%; 93%). The model was implemented as a calculator that can be used in routine clinical practice.

Щелочная фосфатаза в диагностике заболеваний у детей

Alkaline phosphatase (ALP) is an enzyme that catalyzes the hydrolysis of phosphomonoesters (e.g., the endogenous substrate inorganic pyrophosphate) with optimal activity at alkaline pH values. The level of alkaline phosphate depends on both sex and age and the diagnostic system used. Objective. To compare the reference intervals (RI) of alkaline phosphorus in different commercial laboratories and to verify the existence of a lower limit. Results. When analyzing the obtained data, it was revealed that 8 out of 11 diagnostic laboratories have RI of ALP divided according to sex and age, and there is an indication of the lower limit of norm different from 0. At the same time, 2 laboratories have no division of indicators according to sex and age; one laboratory has no division according to sex (there is only division according to age), the lower limit of RI corresponds to 0. Conclusion. Currently, there are a sufficient number of laboratories determining the concentration of alkaline phosphorus by methods for which there are RIs that have a lower limit and standardized separation by age and sex. However, 3 out of 11 laboratories have RIs for ALP that do not meet accepted standards. This may lead to incorrect interpretation of the results of studies, complicate the diagnosis of disorders of calcium-phosphorus metabolism, in particular, hypophosphatasia, since a decrease in the concentration of ALP is the main biochemical marker of this disease. Key words: hypophosphatasia, reference intervals, alkaline phosphatase

Justification of The Need to Determine the Level Of 25(OH) D 3 In the Blood Serum of Children to Assess the Quality of Rickitis Prevention

It has been established that the formation of rickets is promoted by a low level of the main metabolite of vitamin D, calcium and phosphorus in the blood serum. This was evidenced by the study of the biochemical parameters of the main indicators of calcium-phosphorus metabolism and the content of 25(OH) D 3 in the examined children before vitamin D prophylaxis when compared with the data of healthy children. Treatment with vitamin D 3 , along with restorative therapy, has significantly increased the effectiveness of preventing rickets. At the same time, there was a decrease in alkaline phosphatase, an increase in the content of 25(OH) D 3 in the blood serum, as well as in the level of calcium and phosphorus.