Search Results (50)

Background/Objectives: Chronic kidney disease–mineral and bone disorder (CKD-MBD) and systemic inflammation contribute to mortality in hemodialysis (HD) patients. The primary aim of this study was to determine whether specific CKD-MBD markers and inflammatory biomarkers are associated with increased mortality risk in HD patients. Methods: We conducted a retrospective cohort study on 63 stage 5D CKD patients undergoing maintenance HD. Serum intact parathyroid hormone (iPTH), soluble Klotho, calcium, phosphorus, 25(OH)D (25-hydroxyvitamin D), transforming growth factor-beta (TGF-β), vascular endothelial growth factor (VEGF), C-reactive protein (CRP), and interleukin-6 (IL-6) were analyzed. A Cox regression analysis assessed mortality predictors, and linear regression analysis evaluated CKD-MBD–inflammation correlations. Results: Lower iPTH (<329.3 pg/mL) levels were the only significant mortality predictor (p = 0.042). Other CKD-MBD markers (calcium, phosphorus, 25(OH)D, VEGF, TGF-β) did not impact survival. Soluble Klotho correlated positively with IL-6 (r = 0.57, p < 0.001), suggesting a compensatory inflammatory response. Conclusions: Our findings demonstrate that low iPTH levels and advanced age are independent predictors of mortality in hemodialysis patients. The positive association between soluble Klotho and IL-6 suggests a potential compensatory inflammatory response. These results highlight the need for further research to clarify underlying mechanisms and to explore novel therapeutic strategies. Full article

Suboptimal vitamin D status is commonly observed in primary hyperparathyroidism but is rarely considered in management decisions. The present study aimed to bring additional insights on vitamin D status in primary hyperparathyroidism patients, particularly those presenting with the normocalcemic phenotype. A retrospective study was conducted on 53 confirmed primary hyperparathyroidism patients, stratified into hypercalcemic and normocalcemic groups, hospitalized at the “Pius Brînzeu” Emergency Clinical Country Hospital in Timișoara, Romania. Patients presenting with the normocalcemic phenotype had similar target-organ involvement compared to their counterparts. In this subgroup, 25 hydroxyvitamin D showed an inverse correlation with serum calcium (p = 0.048), and regression analysis identified iPTH and 25OH vitamin D as significant predictors of calcium levels (p < 0.0001; $R^2$ = 0.571). Adenoma volume showed a significant negative correlation with 25OH vitamin D levels (p = 0.021; r = −0.61) but was later found as insignificant after confounder analysis. Postoperative measurements of 25OH vitamin D levels confirmed increasing levels after parathyroidectomy. Our findings highlight a complex relationship between PTH and vitamin D in primary hyperparathyroidism, especially in the often-underdiagnosed normocalcemic phenotype. The inverse correlation between vitamin D and calcium suggests altered homeostasis, rather than true deficiency. Full article

Background/Objectives: In situ preservation is the primary strategy to preserve parathyroid gland (PG) function during thyroid surgery, while autotransplantation is used when inadvertent removal or devascularization occurs. Deciding on the optimal approach intraoperatively for exposed PGs remains challenging. This study evaluates intraoperative PG management strategies and long-term outcomes of PG function following total thyroidectomy. Methods: This retrospective study included 543 patients undergoing primary total thyroidectomy, excluding those with comorbid parathyroid disease. A stabbing test assessed the vascular supply of exposed PGs. PGs with fresh blood oozing after the test were preserved in situ; otherwise, they were autotransplanted. Intact parathyroid hormone (iPTH) and ionized calcium (iCa) were measured preoperatively and on postoperative day 1 (PO-1D), and during follow-up. Permanent hypoparathyroidism (PHPS) was defined as iPTH < 15 pg/mL, iCa < 4.2 mg/dL, or continued need for calcitriol or calcium supplementation after a postoperative period of 12 months (PO-12M). The PHPS rate was compared with the corresponding intraoperative PG status. Results: A total of 528 patients were enrolled in this study. At PO-1D, 434 patients (82.2%) had iPTH ≥ 15 pg/mL, 65 (12.3%) had iPTH between 4 and 15 pg/mL, and 29 (5.5%) had iPTH < 4 pg/mL. At PO-12M, 527 patients (99.81%) had iPTH ≥ 15 pg/mL, 1 (0.19%) had iPTH between 4 and 15 pg/mL, and none had iPTH < 4 pg/mL. Five patients (0.95%) were in PHPS after PO-12M. Among the 462 patients with at least one viable PG preserved in situ, the PHPS rate was 0.2%, compared to 6.1% (66 patients) for those without a viable PG preserved in situ (p < 0.001). Conclusions: Permanent hypoparathyroidism is rare when at least one viable PG is preserved in situ during total thyroidectomy. The stabbing test is a simple, useful, and cost-effective method to assess the vascular supply of exposed PGs, providing surgeons with essential information for intraoperative PG management. Full article

Background/Objectives: Chronic kidney disease (CKD), the most common cause of which is hypertension and diabetes, is a recognized risk factor for cardiovascular disease (CVD). This study investigated the association between selected serum biomarkers in the context of intima-media thickness (IMT) changes, a common predictor of subsequent cardiovascular (CV) events. Methods: A total of 251 individuals were enrolled in the study, divided into groups based on the severity of CKD, the presence of CVD, and healthy controls. For this purpose, the data from the following groups of participants were analyzed: (1) end-stage renal disease (ESRD) (n = 106), (2) pre-dialyzed (PRE) (n = 48), (3) patients at stages 1 and 2 of CKD (CKD1-2) (n = 37), (4) patients with CVD and no kidney disease (CARD) (n = 28), and (5) healthy controls (HV) (n = 31). To find markers associated with elevated IMT, the each group with CVD (ESRD, PRE and CARD) was separated into two subgroups with normal and elevated IMT and compared in the relation of the studied serum biomarkers. Results: The findings identified glucose as the only marker exclusively associated with CVD. Markers uniquely linked to CKD included urea, creatinine, eGFR, total protein, CEL, neopterin, total calcium, phosphates, iPTH, sodium, iron, ferritin, and AST. All other markers reflected a combined influence of both CKD and CVD. By comparing patients with normal and elevated IMT, distinct types of CKD–CVD interactions were observed, i.e., independent (additive effects of CKD and CVD) for MPO, ALP, MMP-9, and MMP-9/TIMP-1; combined (enhanced effect due to interactions) for AOPPs and TIMP-1; and conditional (CVD impact specific to CKD patients) for AGEs, 3-NT, magnesium, UIBC, TIBC, ALT, and TIMP-1/MMP-9. However, certain markers, i.e., CML, sRAGEs, carbamylated protein groups, protein carbamylation, hsCRP, TC, HDL-C, LDL-C, TG, IL-18, klotho, FGF-23, klotho/FGF-23 ratio, potassium, NT-proBNP, and AIP were associated with both CKD and CVD, though the exact nature of their interaction could not be determined using IMT as a distinguishing factor. Conclusions: The results showed that relations between IMT and the remaining studied factors were not trivial, and most of the analyzed parameters were altered in CKD patients, especially if compared to patients with CVD but without CKD. IMT cannot be used as a universal CVD marker. Full article

Primary failure of tooth eruption (PFE) is a rare genetic disorder characterized by the failure of teeth to erupt in the absence of obvious physical obstructions, often resulting in a progressive open bite that is resistant to orthodontic treatment. While PFE can be caused by genetic or systemic factors (such as cysts, tumors, and endocrine imbalances), the non-syndromic causes are primarily genetic, with an autosomal dominant inheritance pattern with variable expressivity. Several genes have been closely associated with the non-syndromic PFE form. The PTH1R (parathyroid hormone 1 receptor) is the most commonly PFE-associated gene. Additional genes associated with minor frequency are Transmembrane protein 119 (TMEM119), which reduces the glycolytic efficiency of bone cells, limiting their mineralization capacity and causing bone fragility; Periostin (POSTN), which regulates the extracellular matrix and the bone’s response to mechanical stress; and Lysine (K)-specific methyltransferase 2C (KMT2C), which establishes histone methylation near the Wnt Family Member 5A (WNT5A) gene involved in dental development (odontogenesis). Syndromic forms of PFE are typically associated with complex multisystem disorders, where dental eruption failure is one of the clinical features of the spectrum. These syndromes are often linked to genetic variants that affect ectodermal development, craniofacial patterning, and skeletal growth, leading to abnormal tooth development and eruption patterns. Notable syndromes include GAPO syndrome, ectodermal dysplasia, and cleidocranial dysplasia, each contributing to PFE through distinct molecular mechanisms, such as disruptions in dental structure development, cranial abnormalities, or systemic developmental delays. The main aim of this review is to provide a comprehensive overview of the genetic basis underlying both syndromic and non-syndromic forms of PFE to facilitate precision diagnosis, foster the development of personalized therapeutic strategies, and offer new insights into managing this complex dental anomaly. Full article

Vitamin D, essential for growth and health, is often deficient in Taiwan despite abundant sunlight. Plant-derived vitamin D₂ (ergocalciferol) is bioavailable, environmentally friendly, and cost-effective. This study evaluated the efficacy of enhancing Pleurotus citrinopileatus (PC) mushrooms’ vitamin D₂ content through pulsed ultraviolet (PUV) light and its impact on vitamin D status in humans. In a four-week randomized parallel trial, 36 healthy participants were assigned to three groups: a control group, a group consuming 10 g/day PUV-treated PC (PC-10 g), and a group consuming 100 g/day PUV-treated PC (PC-100 g). Blood samples collected pre- and post-intervention measured serum 25(OH)D₂, 25(OH)D₃, and biochemical parameters. After four weeks, serum 25(OH)D₂ levels significantly increased in the PC-10 g group (1.47 ± 1.42 ng/mL to 9.50 ± 7.10 ng/mL, p = 0.001) and in the PC-100 g group (1.94 ± 2.15 ng/mL to 21.82 ± 16.75 ng/mL, p = 0.002), showing a 10.2-fold rise. The PC-100 g group also experienced a 37.6% reduction in serum intact parathyroid hormone (I-PTH) levels (26.26 ± 9.84 pg/mL to 16.38 ± 5.53 pg/mL). No adverse effects were reported. PUV-treated PC mushrooms significantly increase serum 25(OH)D₂ levels and reduce I-PTH, particularly at higher doses. These findings underscore the potential of vitamin-D-enriched PC as a sustainable, fungi-derived food source for addressing vitamin D deficiency. Full article

Background: Parathyroidectomy (PTX) is generally curative in renal hyperparathyroidism (RHPT) that is refractory to medical treatment in end-stage kidney disease (ESKD) patients. Severe hypocalcemia is a common complication of PTX and results in increased monitoring, interventions, lengths of stay, and costs of care. This study aimed to find the determinants and cutoff values of the biochemical determinants, if any, for severe post-operative hypocalcemia after PTX in adult patients with ESKD. Methods: Severe post-operative hypocalcemia was defined as a lowest adjusted serum calcium level < 2 mmol/L during a hospitalization stay following PTX. Receiver operating curves (ROCs) with area under the curve (AUC) values for pre-operative intact parathyroid hormone (iPTH) and pre-operative alkaline phosphatase (ALP) levels against hypocalcemia were used to determine cutoffs. Generalized linear models using Poisson regression with robust error variance were used to estimate the relative risk of severe post-operative hypocalcemia. Results: In total, 75 patients (38 women, 50.7%) with a mean age of 53.8 ± 11.4 years were enrolled; 43 (57%) patients developed severe hypocalcemia post-PTX and had higher pre-operative serum iPTH and ALP levels, as well as a significantly longer hospitalization post-operation (10.5 vs. 4.3 days, p =< 0.001). A pre-operative iPTH level of >166 pmol/L had an AUC-ROC of 0.73 and 72% sensitivity and 73% specificity, respectively, in predicting severe post-operative hypocalcemia with a relative risk of 2.00 [95% CI 1.27–3.33, p = 0.003]. Conclusions: A pre-operative iPTH level > 166 pmol/L is a strong risk predictor for post-operative severe hypocalcemia. Pre-emptive interventions in this high-risk group could potentially result in a reduced length of stay and lower acuity of care. Full article

Background and Objectives: Uric acid (UA) and the markers of mineral bone metabolism and inflammation are commonly altered in patients with chronic kidney disease (CKD) and are associated with the risk of cardiovascular complications and death. Studies point to a link between high serum UA and mineral bone homeostasis and inflammation, but controversy remains. The aim of this study was to evaluate the relationship between UA levels and mineral bone metabolism and inflammation biomarkers in a sample of Mexican patients with CKD 3a–5. Materials and Methods: This cross-sectional study included 146 Mexican patients with CKD 3a–5. In addition, 25 healthy subjects were included in the study with the aim of generating reference data for comparisons. Metabolic parameters including UA serum concentrations, mineral bone metabolism (parathormone (PTH), fibroblast growth factor 23 (FGF23), calcium, and phosphate), and inflammation (interleukin (IL)-1β, IL-6, and tumor necrosis factor-alpha (TNF-α)) biomarkers were measured in all of the samples and compared as a function of the estimated glomerular function rate (eGFR) or UA levels. Results: Intact PTH, FGF23, and cytokines were higher in advanced CKD stages. Patients with hyperuricemia had significantly higher values of FGF23 and TNF-α compared with those without hyperuricemia. The eGFR was found to be significantly and negatively correlated with all markers. Uric acid was significantly correlated with phosphate, iPTH, FGF23, and TNF-α, whereas iPTH was significantly correlated with FGF23, TNF-α, and FGF23. Finally, a multivariate analysis confirmed the relationship of eGFR with all the tested biomarkers, as well as other relationships of iPTH with UA and TNF-α and of FGF23 with UA and TNF-α. Conclusions: This study supports the relationship between uric acid and levels of mineral bone metabolism and inflammation biomarkers in patients with CKD at middle to advanced stages. In the follow-up of patients with CKD, monitoring and controlling UA levels through nutritional or pharmacological interventions could help in the prevention of alterations related to mineral bone metabolism. Full article

Background: Parathyroid tumors are classified as parathyroid neuroendocrine neoplasia (NEN) by the IARC-WHO classification. These tumors can occur with NENs from other sites, which often require total-body [68Ga]-DOTA-peptides PET/CT. This study aimed to assess the utility of [68Ga]-DOTA-peptide PET/CT in imaging parathyroid NENs and to evaluate the underlying mechanisms. Methods: Fifty patients with primary hyperparathyroidism (PHPT) and parathyroid NENs histologically confirmed as parathyroid adenomas (PAs) were included. PET/CT with [68Ga]-DOTA-peptide was performed in 16 patients with localized PAs, including 10 with MEN1 syndrome. Somatostatin receptor types 2 and 5 (SST2 and SST5) staining was performed on PAs from 48 patients. Somatostatin analogs (SSA) were prescribed in four patients with MEN 1 syndrome and 1 with persistent acromegaly, all with PAs and PHPT. The therapy effects on calcium and parathyroid hormone (iPTH) were evaluated. Results: [68Ga]-DOTA-peptide PET/CT detected 20 PAs with high radiopharmaceutical uptake. SST2 expression was negative on PA cell membranes in all cases and positive on endothelium in 39 (81%) PAs. Membrane SST5 expression was positive in 25 (52%) PAs and endothelial was positive in 40 (83%). Serum calcium levels decreased in patients on SSA therapy, while iPTH did not. Conclusions: PET/CT with [68Ga]-DOTA-peptides can detect parathyroid NENs. The incidental detection of high [68Ga]-DOTA-peptide uptake in the parathyroid region during whole-body PET/CT may prompt biochemical evaluation for PHPT. We suggest that endothelial SST expression mediates high radiopharmaceutical uptake by PAs and that SSA treatment can reduce hypercalcemia in PHPT patients. Full article

Renal osteodystrophy (ROD) represents histological bone changes in patients with chronic kidney disease and is classified according to turnover and mineralization. This cross-sectional study evaluates several bone biomarkers and their ability to discriminate turnover and mineralization defects in hemodialysis (HD) patients. Bone-specific [BSAP] and total [tAP] alkaline phosphatase, procollagen-1 N-terminal propeptide [P1NP], C-terminal cross-linking telopeptide [CTX], intact [iPTH] and whole [wPTH] parathyroid hormone, sclerostin [SOST], fibroblast growth factor 23 [FGF-23], vitamin D, osteoprotegerin [OPG], and receptor activator of nuclear factor κB ligand [RANKL] were collected before the bone biopsy. Thirty-two patients were evaluated by bone histomorphometry, which identified mineralization defects and low and high turnover in 47%, 50%, and 41% of patients, respectively. Bone biomarkers (tAP, BSAP, CTX, P1NP) and hormones (iPTH, wPTH, and SOST) were capable of identifying low and high turnover (AUC > 0.877 and >0.857, respectively, p < 0.001). PTH plus AP had the best accuracy for identifying high turnover. BSAP > 2x, iPTH > 8x, and wPTH > 6x upper limit of normal range identified high turnover. Lower calcium values (Ca < 8.7 mg/dL) were correlated with mineralization defects. On the other hand, FGF-23, OPG, and RANKL did not impact the turnover and mineralization. While bone histomorphometry is not widely available, bone biomarkers such as BSAP, P1NP, PTH, and calcium allow the assessment of turnover and mineralization defects in HD patients. Then, using bone biomarkers may help clinicians define treatments for ROD and osteoporosis and monitor therapeutic response. Full article

Background/Objectives: Numerous risk factors associated with development of cardiovascular disease (CVD) have been unfavorably altered in patients with chronic kidney disease (CKD). Low omega-3 polyunsaturated fatty acid (PUFA) intake and vitamin D deficiency are potential cardiometabolic risk factors in patients with CKD. The aim of this study was to evaluate dietary intake and status of omega-3 PUFA and vitamin D in pre-dialysis and hemodialysis patients and to examine the association of dietary α-linolenic acid (ALA) and fish consumption with blood pressure and carotid intima–media thickness (C-IMT), representing a non-invasive marker of atherosclerosis in CKD patients. Methods: All 77 selected patients (36 pre-dialysis, 41 on hemodialysis) underwent standardized clinical, nutritional, and laboratory assessments. Repeated 24 h recalls were performed to assess dietary intake. The fatty acid profile was determined by gas–liquid chromatography. Results: Inadequate vitamin D intake and vitamin D status were found in 95% of patients. PUFA profiles did not differ between hemodialysis and pre-dialysis participants. Dietary intake of ALA was negatively correlated with systolic blood pressure (SBP) (p = 0.013), C-IMT (p = 0.002), serum CRP (p = 0.044), iPTH (p = 0.01), and 25(OH)D3 (p = 0.006). ALA intake of more than 0.23 g daily was linked with lower SBP (p = 0.001), serum 25(OH)D3 (p = 0.004), and C-IMT (p = 0.002). Conclusions: This study contributes to a better understanding of the relationship between dietary ALA intake and C-IMT in CKD. The results of this study could emphasize the significant role of the high prevalence of vitamin D deficiency and inadequate omega-3 PUFA intake and status regarding CVD health in CKD patients. Full article

Target values for 25-hydroxy vitamin D and 1,25(OH)₂D or 1,25-dihydroxy vitamin D remain a topic of debate among clinicians. We analysed data collected from December 2012 to April 2020 from two cohorts. Cohort A, comprising 455,062 subjects, was used to investigate the relationship between inflammatory indicators (white blood cell [WBC] count and C-reactive protein [CRP]) and 25(OH)D/1,25(OH)₂D. Cohort B, including 47,778 subjects, was used to investigate the connection between 25(OH)D/1,25(OH)₂D and mineral metabolism markers (phosphate, calcium, and intact parathyroid hormone [iPTH]). Quadratic models fit best for all tested correlations, revealing U-shaped relationships between inflammatory indicators and 25(OH)D and 1,25(OH)₂D. Minimal CRP and WBC counts were observed at 1,25(OH)₂D levels of 60 pg/mL and at 25(OH)D levels of 32 ng/mL, as well as of 42 ng/mL, respectively. iPTH correlated inversely with both 1,25(OH)₂D and 25(OH)D, while phosphate as well as calcium levels positively correlated with both vitamin D forms. Calcium-phosphate product increased sharply when 25(OH)D was more than 50 ng/mL, indicating a possible risk for vascular calcification. Multiple regression analyses confirmed that these correlations were independent of confounders. This study suggests target values for 25(OH)D between 30–50 ng/mL and for 1,25(OH)₂D between 50–70 pg/mL, based particularly on their associations with inflammation but also with mineral metabolism markers. These findings contribute to the ongoing discussion around ideal levels of vitamin D but require support from independent studies with data on clinical endpoints. Full article

The choice of dialysate buffer in hemodialysis is crucial, with acetate being widely used despite complications. Citrate has emerged as an alternative because of its favorable effects, yet concerns persist about its impact on calcium and magnesium levels. This study investigates the influence of citrate dialysates (CDs) with and without additional magnesium supplementation on CKD-MBD biomarkers and assesses their ability to chelate divalent metals compared to acetate dialysates (ADs). A prospective crossover study was conducted in a single center, involving patients on thrice-weekly online hemodiafiltration (HDF). The following four dialysates were compared: two acetate-based and two citrate-based. Calcium, magnesium, iPTH, iron, selenium, cadmium, copper, zinc, BUN, albumin, creatinine, bicarbonate, and pH were monitored before and after each dialysis session. Seventy-two HDF sessions were performed on eighteen patients. The CDs showed stability in iPTH levels and reduced post-dialysis total calcium, with no significant increase in adverse events. Magnesium supplementation with CDs prevented hypomagnesemia. However, no significant differences among dialysates were observed in the chelation of other divalent metals. CDs, particularly with higher magnesium concentrations, offer promising benefits, including prevention of hypomagnesemia and stabilization of CKD-MBD parameters, suggesting citrate as a viable alternative to acetate. Further studies are warranted to elucidate long-term outcomes and optimize dialysate formulations. Until then, given our results, we recommend that when a CD is used, it should be used with a 0.75 mmol/L Mg concentration rather than a 0.5 mmol/L one. Full article

This retrospective study aimed to compare risk factors for vascular calcification (VC) between pre-hemodialysis (HD) and prevalent HD adult patients while investigating associations with calcification biomarkers. Baseline data from 30 pre-HD and 85 HD patients were analyzed, including iPTH, vitamin D, FGF 23, fetuin-A, sclerostin, and VC scores (Adragao method). Prevalence of VC was similar in both groups, but HD patients had more frequent VC scores ≥ 6. Pre-HD patients were older, with higher prevalence of hypertension and less frequent use of calcium phosphate binders. Both groups showed similar patterns of hyperphosphatemia, low vitamin D, and iPTH. Fetuin-A and sclerostin levels were higher in pre-HD, while FGF 23 was elevated in HD patients. Higher VC risk in pre-HD patients was associated with male gender, older age, lower fetuin-A and higher sclerostin, lower ferritin, and no vitamin D treatment, while in HD patients with higher sclerostin, FGF 23 and urea, and lower iPTH. Conclusion: Biomarkers could be measurable indicators of biological processes underlying VC in CKD patients that may serve as a potential guide for considering personalized therapeutic approaches. Further studies are needed to elucidate the underlying pathways. Full article

The management of hyperparathyroidism (intact parathyroid hormone (iPTH) serum levels > 585 pg/mL), frequently focuses on the appropriate control of mineral and bone markers, with the decrease in serum and dietary phosphorus as two of the targets. We aimed to investigate the association between iPTH, serum phosphorus levels and dietary intake. This was a cross-sectional, multicenter, observational study with 561 patients on hemodialysis treatment. Clinical parameters, body composition and dietary intake were assessed. For the analysis, patients were divided into three groups: (a) iPTH < 130, (b) iPTH between 130 and 585 and (c) iPTH > 585 pg/mL. The association between PTH, serum phosphorus and dietary intake was analyzed using linear regression models. In the whole sample, 23.2% of patients presented an iPTH > 585 pg/mL. Patients with higher iPTH levels were those with longer HD vintage and lower ages, higher serum phosphorus, serum calcium, Ca/P product, albumin and caffeine intake, and a lower dietary intake of phosphorus, fiber, riboflavin and folate. Higher serum phosphorus predicted higher iPTH levels, even in the adjusted model. However, lower dietary phosphorus and fiber intake were predictors of higher iPTH levels, including in the adjusted model. Our results bring new data to the relationship between dietary intake and iPTH values. Despite higher serum phosphorus being observed in patients with HPTH, an opposite association was noted regarding dietary phosphate and fiber. Full article