Tatyana Simeonova

Fibroblast growth factor 23 (FGF23) and osteocalcin are involved in mineral and bone metabolism, but their relationship in chronic kidney disease (CKD) remains insufficiently characterized. This cross-sectional study investigated the association between FGF23 and undercarboxylated osteocalcin (Glu-OC) and whether this association persisted after accounting for kidney function. The study included 80 adults: 12 healthy controls and 68 patients with non-dialysis CKD stages G1–G4. Associations were assessed using Spearman correlation, partial correlation adjusted for estimated glomerular filtration rate (eGFR), and complementary multivariable linear regression models. Among patients with CKD, FGF23 was inversely correlated with eGFR (ρ = −0.346, p = 0.004) and Glu-OC (ρ = −0.344, p = 0.004), and positively correlated with serum creatinine (ρ = 0.299, p = 0.013). The inverse association between FGF23 and Glu-OC persisted after adjustment for eGFR (partial ρ = −0.475, p < 0.001). In the multivariable regression models, Glu-OC was inversely associated with FGF23 (standardized β = −0.258, p = 0.024), whereas alkaline phosphatase was positively associated with FGF23 (β = 0.369, p = 0.001). In the model with Glu-OC as the dependent variable, FGF23 (β = −0.266, p = 0.020) and serum calcium (β = −0.366, p = 0.002) were inversely associated with Glu-OC. Significant inverse correlations between FGF23 and Glu-OC were observed in CKD stages G1–G3, but not in stage G4 or the control group. These findings support an association between FGF23 and Glu-OC in non-dialysis CKD and provide a rationale for further investigation of a potential FGF23–Glu-OC axis in CKD-associated mineral and bone disorder (CKD-MBD). Longitudinal and mechanistic studies are needed to clarify the nature and clinical relevance of this association.

Introduction: FGF23 and osteocalcin are important regulators of mineral and bone metabolism. The association between FGF23 and undercarboxylated osteocalcin (Glu-OC) in chronic kidney disease (CKD) remains insufficiently understood. This study aimed to investigate the association between FGF23 and Glu-OC and assess whether it is independent of kidney function. Methods: This cross-sectional study included 80 adults: 12 healthy controls and 68 patients with non-dialysis CKD stages G1–G4. FGF23, Glu-OC, calcium, phosphate, PTH, and bone metabolism markers were measured. Associations were assessed using Spearman correlation, partial Spearman correlation adjusted for eGFR, and multivariable linear regression. Results: FGF23 was inversely correlated with eGFR (ρ = −0.346; p = 0.004) and positively correlated with creatinine (ρ = 0.299; p = 0.013). FGF23 was inversely associated with Glu-OC (ρ = −0.344; p = 0.004), with the association becoming stronger after adjustment for eGFR (partial ρ = -0.477; p < 0.001). In complementary multivariable models, the inverse association between FGF23 and Glu-OC persisted: Glu-OC was associated with FGF23 (β = −0.258; p = 0.024), along with ALP (β = 0.369; p = 0.001), while FGF23 was associated with Glu-OC (β = −0.266; p = 0.020), along with calcium (β = −0.366; p = 0.002). Conclusion: FGF23 is independently and inversely associated with Glu-OC in non-dialysis CKD, and this relationship persists after adjustment for kidney function. These findings support an association between FGF23 and Glu-OC in CKD–mineral and bone disorder (CKD-MBD).

Chronic kidney disease (CKD) affects over 10% of the global population, posing significant challenges due to its asymptomatic nature in early stages and progressive deterioration of renal function. The identification of reliable biomarkers for early diagnosis and monitoring of disease progression is crucial for improving prognosis and treatment. Neutrophil gelatinase-associated lipocalin (NGAL) is a promising candidate, already validated as a marker for acute kidney injury. Purpose: This study aimed to evaluate the potential of serum NGAL levels as a biomarker for diagnosis and monitoring the progression of CKD. Material/Methods: Seventy-one adult Caucasian patients at CKD stages G1–G4 according to the KDIGO criteria were divided into three groups: Group 1 (eGFR ≥90 mL/min/1.73m²), Group 2 (eGFR 45–89 mL/min/1.73m²), and Group 3 (eGFR 15–44 mL/min/1.73m²). Blood samples were collected and analyzed via standard biochemical and immunological techniques. Serum NGAL levels were measured using ELISA. Results: NGAL levels increased significantly with disease progression and strongly correlated with declining eGFR. Higher NGAL levels were linked to elevated serum creatinine and inflammatory markers, indicating progressive damage to the kidney tissue against the backdrop of persistent systemic inflammation. Conclusions: As a biomarker, NGAL has significant potential for identifying and monitoring kidney damage. Its application in clinical settings could complement and improve existing methods for diagnosing and observing CKD.

Vitamin K2 plays a key role in calcium homeostasis through activation of VKDP, including matrix Gla protein, a potent inhibitor of vascular calcification. Impaired vitamin K2 status results in increased circulating levels of inactive dephosphorylated uncarboxylated MGP (dp-ucMGP), which serves as a marker for vitamin K2 deficiency. CKD patients are at particularly high risk of vitamin K2 deficiency and its related complications. Purpose: To assess vitamin K2 status indirectly by measuring plasma dp-ucMGP levels in patients with pre-dialysis CKD. Material/Methods: This cross-sectional study included 71 adult Caucasian patients with pre-dialysis CKD stages G1–G4, classified according to KDIGO criteria. Participants were divided into three groups based on estimated glomerular filtration rate (eGFR). Serum creatinine, calcium, inorganic phosphate, and plasma dp-ucMGP levels were measured. Statistical analyses were performed using appropriate parametric and non-parametric tests. Results: Significant differences were observed among the groups in age, renal function parameters, serum calcium, and phosphate levels (p < 0.05). Plasma dp-ucMGP concentrations did not differ significantly between CKD stages. However, when compared with recalculated reference values reported in the literature, dp-ucMGP levels in all groups were elevated, suggesting functional vitamin K2 deficiency. Sex-specific analysis revealed significantly higher dp-ucMGP levels in females with preserved to moderately reduced renal function, while no sex-related differences were observed in advanced CKD. Conclusion: Patients with pre-dialysis CKD demonstrated poor vitamin K2 status, as reflected by elevated dp-ucMGP levels. These findings support growing evidence that vitamin K2 deficiency is common and clinically relevant in the earlytages of CKD.

Chronic kidney disease (CKD) is associated with chronic inflammation and metabolic dysregulation. While endothelin-1 (ET-1) has been extensively studied, the role of endothelin-2 (ET-2) in CKD remains poorly understood. This cross-sectional study included 76 participants, 12 healthy controls and 64 CKD patients, stratified into three groups based on estimated glomerular filtration rate (eGFR): Group 1 (eGFR ≥ 90 mL/min/1.73 m²), Group 2 (eGFR 45–89 mL/min/1.73 m²), and Group 3 (eGFR 15–44 mL/min/1.73 m²). Serum concentrations of ET-1, ET-2, ET-3, uric acid (UA), and inflammatory markers (hsCRP and IL-6) were measured. ET-2 levels were significantly higher in the advanced CKD group (median 24.49 pg/mL) compared to controls (median 19.32 pg/mL; p = 0.030). No significant differences were observed for ET-1 or ET-3 across groups. ET-2 levels positively correlated with UA (rho = 0.243, p = 0.036), hsCRP (rho = 0.241, p = 0.039), and IL-6 (rho = 0.244, p = 0.038). These findings suggest that ET-2 may represent a potential biomarker reflecting metabolic and inflammatory dysregulation in CKD and highlight its possible relevance in disease severity assessment.

Въведение: Витамините К2 и Д играят централна роля в метаболизма на калция и си взаимодействат синергично в поддържането на здравето на костите и сърдечно-съдовата система. Витамин Д стимулира синтеза на протеини, които се активират от витамин К2-зависимо карбоксилиране. Ефектите на витамин К2 върху калциевия метаболизъм, костния търновър и потенциалната му роля в превенцията и лечението на остеопорозата не са напълно изяснени. Цел: Да изследваме нивата на витамините К2 и Д при пациентки с ОП и жени в менопауза и да проучим влиянието им върху костния търновър. Материали и методи: Изследвани бяха 48 жени в менопауза, разпределени в две групи след измерване на КМП на гръбнака с ДХА: работна група, 26 жени с ОП на възраст 65.62±9.2 г. и контролна група от 22 жени без ОП на възраст 63.55±8.7 г. Бяха измерени плазмените концентрации на калций, фосфати, АФ, витамин Д, ПТХ, OC, ucOC. Витамин К2 статуса беше оценен индиректно чрез съотношението ucOC/OC. Резултати: Измерените показатели не показват сигнификантни разлики в двете групи. И в двете групи съотношението ucOC/OC е високо и показва дефицит на витамин К2. Нивата на витамин Д показват недостатъчност. В групата с ОП, ОС показва позитивна корелация с витамин Д (p = 0.015) и с АФ (p = 0.025). UcOC показва позитивна корелация с витамин Д (p = 0.033). UcOC/OC показва висока негативна корелация с ОС (p < 0.001) и негативна корелация с АФ, (p = 0.043). Заключение: Данните ни показват лош витамин К2 и Д статус. В групата с постменопаузална ОП двата витамина повлияват костния търновър чрез взаимосвързаните нива на ПТХ, АФ и ОС, което подтиска функцията на остеобластите и нарушава баланса между костно образуване и резорбция в полза на резорбцията.

Background: The identification of reliable biomarkers for early diagnosis and monitoring of chronic kidney disease (CKD) progression is crucial for improving prognosis and treatment. Neutrophil gelatinase-associated lipocalin (NGAL) is a promising candidate, already validated as a marker for acute kidney injury. This study evaluates NGAL's potential as a biomarker for early diagnosis and monitoring the progression of CKD. Seventy-one patients at CKD stages G1–G4 according to the KDIGO criteria were divided into three groups: Group 1 (eGFR ≥90 mL/min/1.73m²), Group 2 (eGFR 45–89 mL/min/1.73m²), and Group 3 (eGFR 15–44 mL/min/1.73m²). Blood samples were collected and analyzed via standard biochemical and immunological techniques. Serum NGAL levels were measured using ELISA. Results: NGAL levels increased significantly with disease progression and strongly correlated with declining eGFR. Higher NGAL levels were linked to elevated serum creatinine and inflammatory markers, indicating progressive damage to the kidney tissue against the backdrop of persistent systemic inflammation. Conclusions: NGAL demonstrates considerable potential as a biomarker for early detection and monitoring of kidney damage progression. Its use in clinical practice could enrich the traditional methods of diagnosis and monitoring of patients with CKD.

Vitamin K2 deficiency is associated with arterial calcification, which is a significant problem in patients with chronic kidney disease. It occurs more rapidly and earlier and appears to be an independent risk factor for higher morbidity and mortality. The ucMGP is considered to be a biomarker for indirect measurement of vitamin K2 status. Purpose: Our study aimed to measure ucMGP levels in patients at different stages of CKD and to evaluate its potential role as a biomarker of vitamin K2 status. Material/Methods: Sixty-seven patients aged between 31 – 87 years took part in the study. They were divided into groups according to glomerular filtration rate: Group I, with GFR ≥90 ml/min, Group II, with GFR 89 – 45 ml/min, Group III, with GFR 44 – 15 ml/min. Venous blood was tested for calcium, phosphate, creatinine and ucMGP. Results: Serum calcium and phosphate levels were within the reference ranges across all groups. Phosphate levels showed a progressive increase, with significantly lower levels in Group III. Mean ucMGP levels decreased from Group I to Group III, although these differences did not reach statistical significance. In Group I, women had significantly lower ucMGP concentrations compared to men. The incidence of CVD increased significantly with the progression of renal failure. Participants with CVD in Group I demonstrated significantly higher ucMGP concentrations compared to Group III. Conclusions: Uncarboxylated MGP can provide information about vitamin K2 and its carboxylation, but it is not a specific or reliable marker of vitamin K2 status.

Introduction: Chronic kidney disease (CKD) patients are at high risk for cardiovascular disease, largely due to the presence of vascular calcification and its associated complications. Undercarboxylated matrix Gla protein (ucMGP), which inhibits vascular calcification, plays a crucial role in preventing this condition. Aim: Our study aimed to compare ucMGP levels in CKD patients with preserved and reduced renal function and to evaluate its role as a biomarker for cardiovascular risk. Materials and methods: We studied 84 patients with predialysis CKD. They were divided into two groups according to the kidney function: Group I – patients with preserved renal function (GFR ≥ 90 ml/min) and Group II – patients with mild to severely decreased renal function (GFR between 15 and 89 ml/min). Blood samples were analyzed using the Cobas E 311 automated analyzer and the ucMGP levels were measured using an ELISA kit from Abbexa, UK. Results: In Group I, CVD patients had significantly higher inorganic phosphates, blood urea nitrogen and serum creatinine. In Group II, CVD patients had significantly higher ucMGP concentrations. UcMGP levels were associated with age and CVD in Group II and highly correlated with inorganic phosphate and serum creatinine levels in Group I. Conclusions: UcMGP levels show a significant increase in CKD patients with CVD and are strongly connected to various renal function indices, indicating its potential as a biomarker for cardiovascular risk assessment.

Background: Chronic kidney disease (CKD) patients have an increased risk of cardiovascular disease (CVD), necessitating effective risk assessment methods. This study evaluates the calcium–phosphorus product (Ca × P) to estimated glomerular filtration rate (Ca × P/eGFR) ratio as a potential biomarker for predicting CV risk in pre-dialysis CKD patients. Methods: Eighty-four CKD patients in stages G1–G4, according to the KDIGO criteria, were classified into CVD (n = 43) and non-CVD (n = 41) groups. Biochemical parameters, including serum creatinine (SCr), blood urea nitrogen (BUN), calcium (Ca), inorganic phosphate (Pi), parathyroid hormone (PTH), alkaline phosphatase (ALP), Ca × P, eGFR, and the Ca × P/eGFR ratio, were measured and calculated. Statistical analyses were performed to identify predictors of CV risk and evaluate the diagnostic reliability of the Ca × P/eGFR ratio for predicting the risk. Results: Significant differences were observed in SCr, BUN, eGFR (p < 0.001), and the Ca × P/eGFR ratio (p = 0.007) between the groups. Regression analysis indicated the Ca × P/eGFR ratio as a significant CVD risk predictor (p = 0.012, OR = 1.206, 95% CI: 1.042–1.395). Receiver Operating Characteristic (ROC) curve analysis revealed an AUC of 0.751 (p < 0.001, 95% CI: 0.645–0.857), with a sensitivity and specificity of the method of 74.4% and 70.7%, respectively. Significant correlations were found between the Ca × P/eGFR ratio and SCr, BUN, UA, Ca, Pi, PTH, and ALP. Conclusions: The Ca × P/eGFR ratio may serve as a significant predictor of CVD risk in pre-dialysis CKD patients, suggesting that its integration into routine evaluations could enhance CV risk stratification and management.