Mineral Metabolism Research Articles

Exploring the interaction and impact of probiotic and commensal bacteria on vitamins, minerals and short chain fatty acids metabolism

There is increasing evidence that probiotic and commensal bacteria play a role in substrate metabolism, energy harvesting and intestinal homeostasis, and may exert immunomodulatory activities on human health. In addition, recent research suggests that these microorganisms interact with vitamins and minerals, promoting intestinal and metabolic well-being while producing vital microbial metabolites such as short-chain fatty acids (SCFAs). In this regard, there is a flourishing field exploring the intricate dynamics between vitamins, minerals, SCFAs, and commensal/probiotic interactions. In this review, we summarize some of the major hypotheses beyond the mechanisms by which commensals/probiotics impact gut health and their additional effects on the absorption and metabolism of vitamins, minerals, and SCFAs. Our analysis includes comprehensive review of existing evidence from preclinical and clinical studies, with particular focus on the potential interaction between commensals/probiotics and micronutrients. Finally, we highlight knowledge gaps and outline directions for future research in this evolving field.

Prevalence and effects of Vitamin D receptor polymorphism on bone mineral density and metabolism in patients with systemic sclerosis: a preliminary study

Patients with systemic sclerosis (SSc) have a disproportionately high prevalence of reduced bone mineral density (BMD). Polymorphisms of the vitamin D receptor (VDR) gene have been associated with osteoporosis in patients with autoimmune diseases. The aim of this study was to investigate the prevalence and possible effects of VDR polymorphism on BMD and bone metabolism in patients with SSc. In patients with SSc measurement of BMD was performed using dual-energy X-ray absorptiometry. VDR polymorphisms (FokI, BsmI) were genotyped using restriction fragment length polymorphism analysis. Markers of bone metabolism (calcium, osteocalcin, β-crosslaps) were determined. Primary endpoint was the prevalence of VDR gene polymorphisms and the association with reduced BMD. Secondary endpoints included associations between bone metabolism and VDR gene polymorphism. 79 Caucasian patients with SSc were included. Overall, 83.5% had reduced BMD (51.9% osteopenia, 31.6% osteoporosis). The prevalence of VDR gene polymorphism (73% BsmI, 77% FokI) was comparable to studies in healthy and rheumatic populations. The homozygous presence of FokI polymorphism, but not BsmI, was significantly associated with reduced axial BMD. Fokl polymorphism was significantly associated with reduced CTX levels, although changes remained within the reference limits. VDR polymorphisms can frequently be found in patients with SSc in comparable prevalence to healthy and rheumatic populations. The homozygous presence of FokI polymorphism, but not BsmI, was significantly associated with reduced axial BMD. This could be a possible contributor for the high prevalence of reduced BMD in 83.5% of patients with SSc in this study.Trial registration. DRKS00032768, date: 05.10.2023, retrospectively registered.

Application of artificial intelligence to chronic kidney disease mineral bone disorder.

The global derangement of mineral metabolism that accompanies chronic kidney disease (CKD-MBD) is a major driver of the accelerated mortality for individuals with kidney disease. Advances in the delivery of dialysis, in the composition of phosphate binders, and in the therapies directed towards secondary hyperparathyroidism have failed to improve the cardiovascular event profile in this population. Many obstacles have prevented progress in this field including the incomplete understanding of pathophysiology, the lack of clinical targets for early stages of chronic kidney disease, and the remarkably wide diversity in clinical manifestations. We describe in this review a novel approach to CKD-MBD combining mathematical modelling of biologic processes with machine learning artificial intelligence techniques as a tool for the generation of new hypotheses and for the development of innovative therapeutic approaches to this syndrome. Clinicians need alternative targets of therapy, tools for risk profile assessment, and new therapies to address complications early in the course of disease and to personalize therapy to each individual. The complexity of CKD-MBD suggests that incorporating artificial intelligence techniques into the diagnostic, therapeutic, and research armamentarium could accelerate the achievement of these goals.

Short-term effects of dapagliflozin on biomarkers of bone and mineral metabolism in patients with diabetic kidney disease: A prospective observational study

BackgroundThere is still a lack of information regarding the impact of sodium-glucose cotransporter 2 inhibitors (SGLT2i) on bone and mineral metabolism in patients with diabetes and chronic kidney disease (CKD). Therefore, we aimed to investigate the effects of SGLT2i in a cohort of patients suffering from diabetic kidney disease (DKD). MethodsIn this prospective observational study, patients with type 2 diabetes and biopsy-proven diabetic nephropathy or presumptive DKD with eGFR levels ≥20 ml/min/1.73m2 and 25-OH vitamin D levels ≥20 ng/dl were included. 41 used SGLT2i (study group) and 39 continued their current treatment regimens (control group). Serum FGF-23, sclerostin, osteoprotegerin (OPG), and hydroxyproline levels were measured at baseline, 1 month and 3 months after treatment. ResultsMean age of all patients was 67±9.3 years, and 48 (60%) were female. All patients in the study group used dapagliflozin. Taking into account the renal functions at the commencement of the study, the eGFR values for the study group and the control group were 51.2±15.6 and 44.6±16.9ml/min/1.73m2, respectively (p=0.01). After three months, these values were observed to be 47.4±16.7 and 44.3±18.8 ml/min/1.73m2 (p=0.43), respectively. At baseline, OPG levels were higher in the study group (p=0.025) but there were no differences between the groups in terms of FGF-23 and sclerostin levels (p=0.670 and p=0.467, respectively). Levels of OPG, FGF-23, and sclerostin significantly decreased throughout 3 months of treatment with dapagliflozin (p<0.001 for all). Hydroxyproline levels also declined but did not reach to statistical significance (p=0.075). Multiple linear regression models revealed that treatment with SGLT2i was associated with the change in levels of sclerostin (β=0.303, p=0.011) and OPG (β=0.210, p=0.010), but not with FGF-23 (β=0.089, p=0.150). ConclusionsFGF-23, sclerostin and OPG levels significantly declined after treatment with dapagliflozin for 3 months.

Dynamic Single Cell Transcriptomics Defines Kidney FGF23/KL Bioactivity and Novel Segment-Specific Inflammatory Targets.

Inflammation and elevated FGF23 in chronic kidney disease (CKD) are both associated with poor patient outcomes and mortality. However, the links between these manifestations and the effects of inflammation on FGF23-mediated mineral metabolism within specific nephron segments remain unclear. Herein, we isolated an inflammatory pathway driven by TNF/NF-κB associated with regulating FGF23 bioactivity. The findings from this study could be important in designing future therapeutic approaches for chronic mineral diseases, including potential combination therapies or early intervention strategies. We also suggest that further studies could explore these pathways at the single cell level in CKD models, as well as test translation of our findings to interactions of chronic inflammation and elevated FGF23 in human CKD kidney datasets.

Insight into the potential of bone turnover biomarkers: integration in the management of osteoporosis and chronic kidney disease-associated osteoporosis.

Disturbances in mineral and bone metabolism occurring in osteoporosis and chronic kidney disease-associated osteoporosis place patients at high risk of fracture making these conditions a major public health concern. Due to the limited use of bone histomorphometry in clinical practice, the gold standard for assessing bone turnover, extensive efforts have been made to identify bone turnover markers (BTMs) as noninvasive surrogates. Since the identification of certain commonly used markers several decades ago, considerable experience has been acquired regarding their clinical utility in such bone disorders. Mounting evidence suggested that BTMs represent a simple, low-risk, rapid and convenient way to obtain data on the skeletal health and that they may be useful in guiding therapeutic choices and monitoring the response to treatment. BTMs could provide clinicians with useful information, independent from, and often complementary to bone mineral density (BMD) measurements. They have proven valuable for monitoring the effectiveness of osteoporosis therapy, as well as promising for discriminating low and high turnover states. Improved performance is observed when BTMs are combined, which may be useful for selecting treatments for chronic kidney disease-bone mineral disorders (CKD-MBD).

Cardiovascular Dynamics in HIV: The Influence of Adrenal Function and Nutritional Status.

This interdisciplinary review explores the intricate nexus between HIV infection, nutrition, adrenal gland function, and cardiovascular health, highlighting a critical aspect of HIV management often overlooked in current literature. With the advent of antiretroviral therapy, the life expectancy of people living with HIV has dramatically improved, transforming HIV into a manageable chronic condition. However, this success brings forth new challenges, notably an increased risk of cardiovascular diseases among people living with HIV. We examine the normal physiology of the adrenal gland, including its role in mineral metabolism, a crucial facet of nutrition. We discuss the evolution of knowledge tying adrenal pathology to cardiovascular disease. We explore the impact of HIV on adrenal gland findings from a gross pathology perspective, as well as the clinical impact of adrenal insufficiency in HIV. The review further elucidates the role of nutrition in this context, considering the double burden of undernutrition and obesity prevalent in regions heavily affected by HIV. By aggregating findings from longitudinal studies and recent clinical trials, the review presents compelling evidence of increased cardiovascular disease among people living with HIV compared with people without HIV. It highlights the critical role of the adrenal glands in regulating nutrient metabolism and its implications for cardiovascular health, drawing attention to the potential for dietary interventions and targeted therapies to mitigate these risks. This review urges a paradigm shift in the management of HIV, advocating for a holistic approach that incorporates nutritional assessment and interventions into routine HIV care to address the complex interplay between HIV, adrenal function, and cardiovascular health. Through this lens, we offer insights into novel therapeutic strategies aimed at reducing cardiovascular risk in people living with HIV, contributing to the ongoing efforts to enhance the quality of life and longevity in this population.

Study of the &lt;i&gt;Quercus cortex&lt;/i&gt; extract combined effect with an enzyme supplement on hematological blood parameters and broilers chicken growth

The use of phytobiotics with other feed additives in agriculture may be useful for improving animal health and productivity, but further research is needed, to consider other combinations of feed additive sharing and to determine the recommended dose to increase the productivity of laying hens and broilers. In this regard, the work considers the combined effect of oak (Quercus cortex) bark extract and enzyme additive on hematological blood parameters and growth of broiler chickens. As a result of the experiment, it was found that the absolute increase in chickens of experimental group compared to the control was 10.94%. The level of total protein on day 21 in the BD+E+QC group was increased by 19.16% (p ≤ 0.05), albumin by 18.87% (p≤0.05), urea by 21.05% (p ≤ 0.05), glucose by 25.25% (p ≤ 0.05). On day 42, there was an increase in total protein by 4.01% (p ≤ 0.05), albumin by 8.31% (p≤0.05) and urea by 9.37% (p≤0.05) in the group BD+E+QC compared to BD. Analysis of mineral metabolism showed an increase in magnesium content in the BD+E+QC group by 24.5%, in calcium – 18.6%, and in phosphorus – 22.0%. The use of this diet didn’t have a negative effect on growth, morphological and biochemical blood parameters and contributed to the improvement of many indicators. From the above, it follows that the use of phytobiotics and enzyme additive can lead to a synergistic effect and a beneficial effect on farm animals.

#1496 High levels of sclerostin promote bone resorption and changes and mineral metabolism

Abstract Background and Aims The physiological function of sclerostin (SOST) remains unknown. It is known that SOST is produced in osteocytes and functions as an inhibitor of the Wnt/β-catenin pathway. Similarly, it is well-established that low levels of SOST lead to bone alterations affecting cortical bone, resulting in osteopetrosis and reduced calciuria. High levels of SOST are associated with osteoporosis. In this study, we aimed to investigate the impact of three elevated doses of SOST on cortical, trabecular, and subchondral bone, as well as its relationship with other parameters of mineral metabolism. Method Bone histomorphometry, mCT, immunohistochemistry, and analysis of mineral metabolism parameters revealed that high doses of SOST over a 14-day period led to a reduction in trabecular bone volume due to a significant increase in bone resorption through the direct activation of osteoclastogenesis. Results Bone resorption, as measured by TRAP activity, was higher in trabecular, cortical, and subchondral bone. Similarly, high doses of SOST increased the number of hypertrophic chondrocytes, consequently expanding the growth plate area. Cortically, positive TRAP staining was observed, suggesting osteocytic osteolysis and trabecularization of cortical bone. The increased bone resorption resulted in a substantial rise in urinary excretion of phosphorus and calcium, accompanied by elevated levels of FGF23 and a significant decrease in PTH. Conclusion The findings suggest that elevated levels of SOST promote bone resorption through the activation of osteoclasts and the generation of osteocytic osteolysis. The increase in calcium and phosphorus levels led to changes in mineral metabolism, indicating a close relationship between SOST and other mineral metabolism parameters.

#2895 Erythropoietin Resistance Index (ERI) between mortality and metabolic changes in a cohort of hemodialysis patients. What acts below the surface?

Abstract Background and Aims The management of anemia in hemodialysis patients (HD-ps) is influenced by many factors, including inflammation, martial balance (MB) and mineral metabolism (MM). Recent data would identify the Erythropoietin Resistance Index (ERI) as an indicator of mortality risk in HD-ps. The objective of the present study was to evaluate the relationship of ERI with inflammation, MB and MM, as well as all-cause mortality in a cohort of HD-ps. Method An observational-retrospective study was performed on 100 HD-ps, excluding those with acute or chronic infections (3 months), neoplasia, or immunosuppressive therapy. Mortality was considered primary outcome along a 2-year follow-up (FU). Results HD-ps, predominantly males, had advanced mean age, good Hb values and fair biochemical control. ERI showed significant correlations with some elements of inflammation, MM and BM (Table 1), including c-terminal fragment of Fibroblast Growth Factor 23 (cFGF23). At multivariate, ERI remained influenced by cFGF23 (p = 0.009), iron (p = 0.002) and transferrin (p = 0.007). Furthermore, after 2 years of FU, 42% of HD-ps died. As shown in Table 2, HD-ps that faced the primary outcome (death) were older, had lower levels of albumin, hemoglobin and transferrin, and higher levels of IL6, parathormone (PTH), reactive C protein (PCR), and ERI (p &amp;lt; 0.035). In multivariate, ERI (p = 0.011), age (p = 0.001) and albumin (p = 0.010) remained significant for the outcome studied. Conclusion Our data, albeit on few HD-ps, show a possible association between ERI and mortality. ERI was found to be related to several factors, including cFGF23, itself a factor implicated in maintaining a baseline inflammatory state. The results suggest the possible presence of some pathological mechanisms that can act silently with a negative impact on survival. Certainly, increased numbers and a prospective design could better clarify the explored relationships in the future.

#1443 Bone and mineral metabolism in patients with nephropathic cystinosis as a function of age and eGFR

Abstract Background and Aims Cystinosis-associated metabolic bone disease (CMBD) is a major challenge in the treatment of patients with infantile nephropathic cystinosis (NC). Study data are limited due to small case numbers, lack of adults or patients on renal replacement therapy and/or inadequate assessment of bone health. Method We investigated markers for CMBD in all age groups (1-44 years; 61% children) and CKD stages 1-5D/T in the largest NC cohort to date with 103 German and Austrian NC patients. Skeletal comorbidity and concentrations of fibroblast growth factor 23 (FGF23), the osteoblast marker bone-specific alkaline phosphatase (BAP), the bone remodeling inhibitor sclerostin, the osteoclast marker tartrate-resistant acid phosphatase 5b (TRAP5b), the soluble receptor activator of nuclear factor kappa B ligand (sRANKL), osteoprotegerin (OPG) and the sRANKL/OPG ratio as surrogates for the regulation of osteoclastogenesis by osteoblasts were determined by ELISA, converted into age- and sex-specific z-scores and compared as a function of eGFR. Multivariable regression analyses were used to identify specific influencing factors associated with biochemical and clinical findings in pre-transplant NC patients. Results Skeletal complications occurred in two-thirds of patients, with the risk being five times higher in adults than in children. Pediatric and adult NC patients with CKD stages 1-4 showed hypophosphatemia and hypocalcemia associated with suppressed FGF23 and PTH levels and elevated BAP concentrations. This was associated with age, eGFR and treatment with phosphate and active vitamin D, suggesting more vigorous treatment of Fanconi syndrome in pre-transplant patients. As indicated by the increased TRAP5b and decreased sRANKL/OPG ratio, osteoclast activity was increased despite counterregulation by osteoblasts, which in conjunction with increased sclerostin activity may have contributed to the progressive bone loss and skeletal comorbidity in our patient cohort. Conclusion Bone health in NC progressively deteriorates with age, largely due to persistent rickets/osteomalacia associated with inadequate treatment of Fanconi syndrome and increased osteoclast activity despite osteoblast counterregulation via OPG/RANKL. Our data suggest that a primary osteoclast defect in NC promotes increased bone resorption, limiting maximal bone mass and leading to progressive bone loss and increased skeletal comorbidity.

#2708 Impact of dialysis modality on bone phenotype

Abstract Background and Aims Literature data suggest that low bone turnover is the prevailing bone phenotype in patients treated with peritoneal dialysis (PD) and point to high sclerostin as the central culprit. Lack of adequate controls, diagnostic heterogeneity, and a changing mineral metabolism landscape and armamentarium call for a cautious interpretation and confirmation in contemporary patients. Method Laboratory parameters of mineral metabolism (biointact parathyroid hormone (PTH), fibroblast growth factor 23 [FGF23] and sclerostin), bone turnover markers (bone alkaline phosphatase [BALP], intact procollagen type I N-terminal propeptide [PINP], tartrate-resistant acid phosphatase 5b [TRAP5b]) and bone mineral density (BMD) were assessed in 636 non-diabetic kidney transplant candidates of whom 447 were treated with hemodialysis (HD) and 189 with PD. A bone biopsy was performed in 204 patients (n = 134 HD; n = 70 PD), with bone sclerostin expression assessed in a subset (n = 52). Results Patients treated with PD had lower levels of PINP (79.6 vs 99.5 ug/L; p &amp;lt; 0.01) and BALP (20.2 vs 23.7 ug/L; p = 0.04) compared to those treated with HD. Histomorphometric parameters of bone formation were numerically lower in patients treated with PD, but significance was not reached. Bone mineralization was impaired in HD patients (osteoid width: 7.90 vs 6.75 µM; p = 0.01; osteoid maturation: 9 vs 6 days; p = 0.03), while frank osteomalacia was rare in both modalities (6.0%, both groups). BMD was higher in patients treated with PD compared to HD at skeletal sites rich in cortical bone (Z-score midshaft radius −0.4 ± 1.3 vs −0.9 ± 1.7; p = 0.04). PTH levels were comparable (150 vs 144 pg/mL, PD vs HD), while patients treated with PD showed higher serum phosphate (4.9 ± 1.3 vs 4.5 ± 1.6 mg/dl; p &amp;lt; 0.01) and FGF23 levels (3852 pg/ml vs 2361 pg/ml; p = 0.01). Circulating (1.82 ng/mL, both groups) and bone tissue expression (205 ± 126 vs 206 ± 112 positive osteocytes per mm2) of sclerostin did not differ between groups. Conclusion Patients treated with PD present a lower bone turnover, better mineralization, and higher cortical BMD than counterparts treated HD. Overall, differences are marginal and most probably clinically irrelevant. We speculate that inferior phosphate control may be in the causal pathway.

#2061 Perirenal fat thickness as a potential marker for cardiovascular risk in chronic kidney disease: the influence of vitamin D analogs

Abstract Background and Aims Patients with CKD show high cardiovascular complication rates. There are classical cardiovascular risk factors, such as obesity, dyslipidemia, and diabetes; however, other cardiovascular disease risk factors are associated with mineral metabolism disorders (phosphorus, hyperparathyroidism, etc.) typically appear in CKD. Due to their pleiotropic effects, vitamin D analogs, such as cholecalciferol, calcitriol, or paricalcitol, have proven effective in controlling bone mineral disease secondary to CKD and cardiovascular pathologies. On the other hand, visceral adiposity has been shown as a risk factor in the general population and in patients with CKD. Specifically, the fat deposited in regions such as the epicardium generates a complex autocrine and paracrine hormonal mechanism that has been associated with cardiovascular complications. Although it has not been widely evaluated, the adipose tissue surrounding the kidneys (perirenal fat [PRF]) could provide additional information of interest in the CKD population. The aim of the study is to assess the relationship between cardiovascular disease, PRF, and the effect of therapeutic interventions for bone and mineral metabolism in patients with CKD. Method This prospective observational and cross-sectional study was designed to evaluate the usage of vitamin D analogs in patients with CKD, focusing on cardiovascular history and PRF accumulation. All the patients were evaluated at the outpatient clinic in Consuelo Hospital in Valencia Spain (January-November 2022). Eighty-three patients with different grades of CKD (G1A1 to G5A3 not on dialysis) were included and follow-up for 24 months. All the patient's data from electronic medical and analytical records were entered into a protocol sheet. The patients that meet the inclusion criteria (eGFR ≤90 or&amp;gt;15 ml/min/1.73 m2; age ≥18 years at the time of signing informed consent, and a life expectancy higher than 1 year) were eligible to participate in the study. As exclusion criteria, patients with an active inflammatory process such as infection, active cancer, or other inflammatory states were excluded beyond those mentioned in inclusion. Patients with an AKI, ADPKD, or CKD requiring RRT were also excluded. Patients were discriminated according to their history of cardiovascular disease (coronary artery disease, stroke, and peripheral vascular disease) and the use of Vitamin D analogs (Cholecalciferol, Calcitriol, and Paricalcitol). The thickness of the PRF was measured in centimeters (cm) through a B-mode ultrasound with a 3.5-MHz convex transductor (Alpinion®; Alpinion Medical Systems, Korea). Patients underwent a bilateral renal ultrasound, and the kidneys were measured anteroposteriorly, transversally, and longitudinally. PRF was measured in the distal third between the cortex and the hepatic border and/or spleen. Results The mean age of the patients was 58.3 ± 16 years. Patients with a cardiovascular disease history showed significantly higher levels of urea (62.0 vs 45.2 mg/dl, p &amp;lt; 0.05), uric acid (5.5 vs 4.3 mg/dl; p &amp;lt; 0.03), intact parathyroid hormone (iPTH) (186.2 vs 65.2 pcg/dl; p0.05) and decreased eGFR (53.55 vs 89.00 ml/min/1.73 mts2). The mean PRF thickness (0.99 vs 0.80 cm; SD ± 0.30; p0.05) was also observed to be elevated with respect to the group who had no previous cardiovascular events (Fig. 1). Moreover, this group showers higher levels (1.2 vs 7.1; p &amp;lt; 0.005) of CRP. Those patients on oral treatment with Paricalcitol (1 mcg/day) had lesser PRF accumulation than those treated with Cholecalciferol (1000 IU/day) or Calcitriol (0.5 mcg/day) (p &amp;lt; 0.05) (Fig. 2). It was not adjusted for confounding factors such as weight, height, or BMI. Conclusion These results show a close relationship between the presence of cardiovascular disease history and a higher accumulation of PRF. The mechanisms by which paricalcitol could influence the decrease in PRF are so far unknown, however, some studies have shown an association between PTH elevation and obesity. Finally, achieving a decrease in the latter could reduce visceral adipose tissue, thus reducing the cardiovascular risk in CKD-affected patients.

#1736 Correlation between chronic kidney disease-mineral and bone disorder parameters and clinical events in hemodialysis patients

Abstract Background and Aims Patients with chronic kidney disease experience mineral and bone metabolism alterations, collectively known as Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD), linked to elevated cardiovascular mortality. A significant biochemical change is the development of secondary hyperparathyroidism—an adaptive response to uremic conditions that, when surpassing critical thresholds, becomes maladaptive, heightening clinical risk. Presently, optimal parathyroid hormone (PTH) values for hemodialysis (HD) patients lack a clear definition, with recent evidence challenging international guideline limits. This study aimed to evaluate the impact of PTH values on mortality in a population of patients in HD. Method A prospective observational study involving chronic hemodialysis patients commenced in January 2020, with a 40-month follow-up for mortality recording. Exclusion criteria comprised parathyroidectomy, primary hyperparathyroidism evidence, prior kidney transplant, or transplant plans within three months. Clinical and biochemical data, aligned with the 2017 KDIGO guidelines for PTH, calcium (Ca), and phosphorus (Ps) target values, were recorded. Our laboratory PTH values ranged from 25 to 88 pg/ml, and stable PTH values within 180 to 700 pg/ml were deemed adequate in HD patients. Patients were categorized based on the average of three values over 12 months for PTH, Ca, and Ps parameters. Results One hundred patients (average age: 71 ± 13.59) were enrolled. Seventy-seven percent achieved PTH targets (180-700 pg/ml), 73% for Ca, and 19% for phosphorus (Table 1). During follow-up, 36 deaths (36%) occurred. While percentages of target achievement were similar between survivor and non-survivor groups, non-survivor patients exhibited higher PTH values (423.08 ± 277 vs. 360.44 ± 214.92; p = 0.05) without differences in Ca and Ps levels between the two groups (Table 2). Stratifying based on the median PTH value (330 pg/ml) revealed higher mortality in patients with PTH &amp;gt; 330 pg/ml (Log-rank test p = 0.05) (Fig. 1). Conclusion Despite comparable target achievements for PTH, Ca, and Ps, deceased patients had elevated average PTH values, especially those exceeding 330 pg/ml, indicating a higher risk of death during our follow-up. In line with recent literature, these findings underscore PTH's role as a uremic toxin, suggesting a revaluation of current PTH targets for hemodialysis patients

#2460 Haemodialysis-related periarticular calcifications as cause of recurrent severe inflammatory state

Abstract Background and Aims End stage chronic kidney disease (CKD) and haemodialysis (HD) are associated with disturbances in mineral and bone turnover ultimately leading to chronic kidney disease–mineral and bone disorder (CKD-MBD), which affects more than 90 % of patients with stage 5D CKD. The primary changes observed in CKD–MBD involve elevated phosphorus levels, decreased calcium levels, insufficient serum vitamin D, and heightened release of parathyroid hormone from the parathyroid glands, leading to secondary hyperparathyroidism. CKD-MBD leads to vascular calcification, increasing cardiovascular risk. There is also a correlation between abnormal bone remodeling activity in CKD-MBD and the likelihood of calcification in soft tissues. In rare instances, profound calcification occurs in periarticular tissues, resulting in severe inflammation and manifesting as systemic disease with articular involvement clinically. The objective of this case report is to demonstrate a recurrent inflammatory condition caused by severe periarticular calcification in a patient on HD. Case report We present a case of a middle-aged white male diagnosed with hypertension, hypercholesterolemia, chronic obstructive pulmonary disease, hepatitis C, and end-stage renal disease caused by hydronephrosis. He was undergoing HD since July 2020. From summer 2021 the patient experienced recurrent fever and arthralgias in the hips, elbows, and shoulders. Frequent acute hospitalizations were needed due to recurring fevers and severe inflammatory response with markedly elevated acute phase reactants (CRP was repeatedly &amp;gt;200 mg/l), raising suspicion of infection. Laboratory and imaging tests however showed no clear signs of infection, and antibiotic therapy was ineffective. An x-ray of the right AC-joint showed multiple periarticular calcifications dorsally from the AC-joint. Later, due to severe pain and swelling an MRI-scan of right elbow joint was conducted, revealing an osteomyelitis-suspect finding of the olecranon, and olecranon bursitis. No bacteria were detected in the punctate of olecranon bursa. X-ray scans of the elbows revealed bilateral soft tissue calcification dorsally from the proximal ulna. The x-ray scan of the right shoulder revealed calcific expansion in the AC-joint area, leading to total destruction of the lateral part of the clavicle. MRI and CT scans showed severe periarticular calcification around AC- and glenohumeral joints without inflammatory involvement of the synovium. Bony erosions were observed due to the pressure of calcified tissue on the bone. Whole-body CT-scan showed no sites of infection but there was a periarticular calcification observed around the hip joints. A PET-CT scan of the whole body, neck, and upper extremities revealed no signs of malignancy or infections, but there was an increased uptake of 18F-fluorodeoxyglucose detected in several periarticular sites, indicating a multi-site inflammatory process resulting from severe periarticular calcifications. A dual-energy CT-scan of upper extremities was performed, excluding the accumulation of monosodium urate crystals. The cycle of multiple hospitalizations and antibacterial therapies was broken with the diagnosis of CKD and HD-related inflammatory periarticular calcification. Initially, the inflammation was addressed with high-dose glucocorticoids. However, the dose was successfully tapered during the first month of treatment, and the patient continued to do well on a maintenance dose of 5 mg/day of prednisolone. Subsequently, hospitalizations, antibiotics, or surgical procedures were no longer required. Conclusion Severe CKD and HD cause disturbances in mineral and bone metabolism, that can lead to periarticular calcification. Like in our presented case, multi-site calcifications may mimic infection or autoimmune rheumatoid conditions making the way to correct diagnosis cumbersome and costly. Imaging techniques help us distinguish periarticular deposits from inflammatory and infectious arthritis. In our case low-dose prednisolone effectively reduced inflammation, obviating hospitalizations and minimizing healthcare burden.

#2223 Glycosylated hemoglobin levels and bone phenotype in patients with end-stage kidney disease

Abstract Background and Aims Diabetes mellitus is common as both cause and comorbidity of patients with chronic kidney disease (CKD). Both diabetes and CKD are states of increased fracture risk compared to healthy controls, with multiple potential contributing mechanisms. In type 2 diabetes, hyperglycemia contributes to the accumulation of advanced glycation end-products and osteocyte dysfunction, and it may play a pathogenic role in bone fragility. In this study, we wanted to examine the association between glycemic status and bone phenotype in patients with end-stage kidney disease (ESKD). Method This is a cross-sectional cohort study of 626 patients with CKD G5-5D referred for kidney transplantation between April 2006 and December 2013. Patients with type 1 diabetes were excluded. Patients were divided into quartiles based on HbA1c. Laboratory parameters of bone mineral metabolism (including biointact parathyroid hormone (PTH), fibroblast growth factor-23 (FGF23), and sclerostin), and bone turnover markers (bone alkaline phosphatase (BALP), trimeric pro-collagen type 1 N-terminal pro-peptide (intact P1NP), and tartrate-resistant acid phosphatase 5b (TRAP5b)) were measured. Bone mineral density (BMD) assessed by dual-energy X-ray absorptiometry (DEXA) (n = 537), bone histomorphometry (n = 180), and bone trabecular score (TBS) (n = 192) were available for subsets of patients. Results The median HbA1c were 4.8% in Q1, 5.1% in Q2, 5.4% in Q3, and 5.9% in Q4. Age and BMI differed across quartiles, with the highest age and BMI in Q4. Differences in bone turnover markers were found, with decreasing bone formation (BALP and intact P1NP) and decreasing bone resorption (TRAP5b) with ascending quartiles (Fig. 1). No differences across quartiles were found for FGF23, or circulating levels of sclerostin; however a weak, positive correlation between HbA1c and sclerostin was noted (rho = 0.08, p = 0.047). Overall, BMD at lumbar spine, femoral neck, and total hip increased across quartiles, the highest values in Q4 (Table 1). There were no differen in bone histomorphometry or TBS based on glycemic status. Conclusion Chronic hyperglycemia associates with suppressed bone turnover and higher BMD in patients with ESKD, even in non-diabetics. Potential mechanisms linking glucose metabolism to bone quantity and quality requires further investigation.

#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.

#2067 Prediction of gastrointestinal bleeding hospitalization risk in hemodialysis using machine learning techniques

Abstract Background and Aims INitiativeS on advancing Patients’ outcomes In REnal disease (INSPIRE) is an academia and industry collaboration set forth to identify critical investigations needed to advance the practice of medicine in nephrology. Gastrointestinal bleeding (GIB) is one of the most common types of bleeding events in the kidney dialysis population [1]. We aimed to develop a model to predict GIB hospitalization risk in a hemodialysis (HD) patient within 180 days. We evaluated advanced machine learning algorithm (XGBoost) and compared it to traditional machine learning algorithm (logistic regression) modeling techniques. Method We used data from a kidney care network from 2017 through 2020. We included data from adult dialysis patients (age ≥18 years). GIB related hospitalization was defined based on international classification of diseases (ICD) diagnosis codes recorded as the primary, secondary, or tertiary discharge reason for hospitalization. Two distinct models were created using XGBoost and logistic regression algorithms and using the same dataset. Both models were evaluated using metrics such as area under the receiver operating curve (AUROC), accuracy, sensitivity, and specificity. Missing data was imputed using mean for quantitative data and mode for qualitative data. The dataset then was randomly divided into 60% training, 20% validation and 20% test dataset. The test data, comprising unseen patients and data was used to evaluate the performance of the model. This means that the model had never encountered the test data during its learning phase, which included training the model and then validating the model. Results The incidence of 180-day GIB hospitalization was 1.12% in the HD population (n = 5 116 with GIB hospitalization/ n = 451 653 without GIB hospitalization), and consistent in the unseen test dataset (n = 465 with GIB hospitalization/ n = 38586 without GIB hospitalization). The XGBoost model showed higher predictive performance compared to logistic regression (Table). The AUROC was 0.72 (95% confidence interval (CI) 0.69, 0.74) for the XGBoost model. In comparison, the AUROC was 0.615 (95% CI 0.60, 0.64) for the logistic regression model. Specificity was 67% versus 58% for the XGBoost model versus logistic regression model respectively. However, sensitivity for both the models was 65%. The top predictors for major GIB were consistent in both models for many factors, yet some factors showed different importance on outcome prediction (Fig. 1). Higher risk of GIB hospitalization was associated with older age, lower ferritin levels, and recent all-cause hospitalizations in both models. The XGBoost showed high importance on outcome prediction for lower hemoglobin and higher serum 25 hydroxy (25OH) vitamin D values, and the logistic regression model showed high importance for higher amounts of saline delivered during an HD treatment and lower intact parathyroid hormone (iPTH) levels. Conclusion We found advanced machine learning prediction modeling (XGBoost) appears suitable for identifying a HD patient at risk for a GIB hospitalization in the next 180 days, and outperforms traditional machine learning (logistic regression) modeling techniques. Although both models showed identical sensitivity, the XGBoost model had higher specificity. Prospective testing is needed to confirm the model's performance. The association between bone mineral metabolism markers and GIB hospitalization risk is unexpected and warrants further investigation.

#129 Impact of Ramadan fasting on bone mineral metabolism in hemodialysis: a multi-center prospective study

Abstract Background and Aims Fasting is fundamental in several major religions and cultural traditions worldwide. In Islam, Ramadan fasting is characterized by daily complete eating and drinking abstinence from the dawn to sunset for an entire lunar month. Sick patients, including patients with advanced chronic kidney disease are not required to fast, however the majority of them are still choose to fast. The Impact of Ramadan fasting on bone health has not been studied prospectively. This study aims to examine the effect of Ramadan fasting on parameters of bone mineral metabolism in patients on hemodialysis. Method : This is a multi-center prospective study on 138 patients with ESKD who are maintained on intermittent hemodialysis for at least six months. Ninety-three (67%) were fasting while 45 patients (33%) did not fast. All patients' demographics, clinical and laboratory parameters were compared before and after the holy month of Ramadan. Serum biochemical parameters included serum sodium, potassium, bicarbonate, chloride, albumin, calcium, phosphorus, magnesium, intact parathyroid hormone (iPTH), FGF23, klotho, sclerostin, bone-specific alkaline phosphatase (BSAP), and tartrate-resistant alkaline phosphatase 5b (TRAP5b). Results The two groups exhibited comparable demographics and clinical parameters at baseline, except for the mean age, which was significantly lower in the fasting group (45.5 vs. 54.4 years, p-value = 0.003) and the non-smoker habit was significantly higher in the fasting group (71% vs. 56%, p-value = 0.02). There was no change in the clinical parameters by the end of Ramadan in both groups including intra-dialytic hypotension, inter-dialytic weight gain, and hypoglycemia. The basic biochemical parameters did not change significantly at the end of Ramadan in both groups, except there was an increased serum albumin level (p-value = 0.04). The BSAP levels significantly went down by the end of Ramadan in the fasting group (p-value = 0.01). The other novel serum biomarkers (FGF23, klotho, sclerostin, and TRAP5b) did not change significantly in both groups. Conclusion This multi-center prospective study demonstrates that Ramadan fasting does not significantly alter the clinical and biochemical parameters in hemodialysis patients, highlighting its safety in this population. Moreover, our findings reveal a noteworthy reduction of the higher BSAP towards normal levels in fasting patients, suggesting a potential benefit of fasting in improving high bone turnover. Further research is warranted to elucidate this phenomenon's underlying mechanisms and long-term implications, which may hold promise for managing bone health in hemodialysis patients during Ramadan fasting.

#2034 CKD-MBD management: results from a national survey on bone turnover biomarkers practice and therapeutic strategies among Italian nephrologists

Abstract Background and Aims Advanced stages of chronic kidney disease (CKD) are constantly characterized by a mineral and bone disorders (MBD) syndrome concerning a complex systemic condition that includes laboratory abnormalities of bone and mineral metabolism involving calcium, phosphorus, parathyroid hormone (PTH), or vitamin D; abnormalities in bone turnover, mineralization, volume, or strength; extra-skeletal calcifications, such as vascular or other soft tissue. CKD-MBD syndrome determines relevant consequences in terms of fragility fractures, cardiovascular events and higher mortality. The nephrologist's awareness of CKD-MBD diagnostic and management tools and therapeutic strategies is key to improving CKD patients’ prognosis and outcomes. Method A new national survey (composed of 17 online questions) was conducted among Italian nephrologists to investigate the reference laboratory availability of bone turnover markers (BTMs), the clinical attitude on secondary hyperparathyroidism (sHPT) management, and the CKD-MBD therapeutic approach in different stages of CKD and dialysis patients. Results 89 Italian nephrologists participated in the survey. The reference laboratories largely fulfill the biomarkers request of ionized calcium (97.7%), phosphorus (100%), PTH (100%), alkaline phosphatase (ALP) (100%), magnesium (100%), 25-OH and 1,25-OH vitamin D levels (92.1%; 53.9%); while most of the hospital laboratories do not regularly support the availability of specific BTMs, both for diagnosis and monitoring the bone resorption and formation (Fig. 1)—such as bone ALP (75.3%), calcifediol (37.1%), calcitriol (40.5%), fibroblast growth factor-23 (FGF-23) (intact 9% and c-terminal 4.5%), vitamin K (33.7%), Klotho (6.75%, soluble 4.5%), osteocalcin (38.2%), matrix gla protein (10.1%), tartrate-resistant acid phosphatase 5b (TRAP-5b) (6.75%), cross-linked collagen type I peptide (CTX) (32.6%) and procollagen type 1 n-terminal propeptide (P1NP) (10.1%). The nephrologist's attitude to start management and treatment of sHPT is revealed to be mainly led by KDOQI (n = 42, 47%) and KDIGO (n = 39, 44%) guidelines considering their PTH cut-off values; in 53.9% of clinicians the measure of PTH levels is then performed every 3 months according to KDOQI guidelines. In relation to the definition of high turnover metabolic bone disease by BTMs, this metabolic pattern is identified in &amp;gt; 50% and 30-40% of patients with CKD 4-5D by 31.5% and 21.4% of nephrologists, respectively. 65% of clinicians currently considered ALP of equal importance as alterations of PTH as a predictor of fracture events. Other biomarkers, such as FGF-23, P1NP or TRAP-5b, emerge to not be still used in regular clinical practice. In patients diagnosed with CKD-MBD and skeletal fragility, 76.4% of nephrologists consider the AIFA (Italian Medicines Agency) note 79 to support osteoporosis treatment. The therapeutic strategies of CKD-MBD include the administration of vitamin D (e.g. cholecalciferol 27-37.1%, calcifediol 9-12.4%, calcitriol 42.7-55.1%) and its analogues (e.g. paricalcitol 23.6-52.8%) and the use of antiresorptive agents (e.g. alendronate 3.4%-23.6%, denosumab 22.5%-30.3%) with variable frequencies among different advanced CKD stages and for those patients on peritoneal or hemodialysis (Fig. 2). Conclusion Results present a suboptimal use of BTMs and a current heterogeneous therapeutic management of CKD-MBD syndrome and renal osteodystrophy in Italian clinical practice. The survey represents a starting point of work to further implement awareness of diagnostic and therapeutic issues of CKD-MBD.