Markers Of Mineral Metabolism Research Articles

#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.

Metabolic response of endangered goats fed spineless cactus associated with Tifton-85 hay or Maniçoba hay

The aim of this study was to evaluate the effects of replacement of Tifton-85 hay by maniçoba hay, in spineless cactus-based diets, on markers of energy, protein, mineral metabolism and serum enzyme activity of Moxotó goats. Sixteen uncastrated male Moxotó breed goats, with 20 months old and initial body weight of 21.7 ± 3.92 kg were used in a randomized blocks design, using the initial weight as the criterion for the formation of blocks, with two treatments and eight replicates per treatment. The experimental treatments consisted of two diets: diets containing Miúda spineless cactus associated with Tifton-85 hay (1) or maniçoba hay (2), with roughage:concentrate ratio of 70:30. Blood samples were collected fortnightly (baseline, 15 days, 30 days and 45 days) during the feedlot period. There was a higher serum concentration of total protein and fructosamine (P < 0.05) in goats that received maniçoba hay. However, there was higher serum gamma-glutamyl transferase (GGT) enzyme activity in goats that ingested Tifton-85 hay (P < 0.05). Concerning to the profile of blood metabolites in the different fortnightly collections, it was possible to verify a significant effect for urea, fructosamine, GGT enzyme activity, K and Cl levels (P < 0.05). In conclusion, Tifton-85 hay and maniçoba hay combined with spineless cactus does not cause metabolic disorders in feedlot native goats.

Associations of Serum Irisin and Fibroblast Growth Factor-21 Levels With Bone Mineral Characteristics in Eumenorrheic Adolescent Athletes With Different Training Activity Patterns.

To describe serum irisin and fibroblast growth factor-21 (FGF-21) concentrations in healthy female adolescents with different training activity patterns and their associations with bone mineral properties and metabolic markers. A total of 62 adolescent girls aged 14-18years were recruited: 22 rhythmic gymnasts, 20 swimmers, and 20 untrained controls. Bone mineral characteristics by dual-energy X-ray absorptiometry, daily energy intake by dietary recall, serum irisin, FGF-21, undercarboxylated osteocalcin, and C-terminal telopeptide of type I collagen were measured in all girls. Whole body and lumbar spine areal bone mineral density and lumbar spine bone mineral content were higher in the rhythmic gymnasts group compared with swimmers and untrained controls groups (P < .05). Serum irisin, FGF-21, undercarboxylated osteocalcin, and C-terminal telopeptide of type I collagen levels were not significantly different between the groups. In the rhythmic gymnasts group, serum FGF-21 concentration was positively correlated with lumbar spine areal bone mineral density independently of confounding factors (r = .51; P = .027). Serum irisin and FGF-21 levels were not different between adolescent eumenorrheic girls with different training activity patterns. FGF-21 was positively associated with lumbar spine areal bone mineral density, which predominantly consists of trabecular bone in adolescent rhythmic gymnasts.

A comparative analysis of serum phosphorus levels and mineral metabolic markers in non-dialysis and dialysis chronic kidney disease patient: a cross-sectional study

Background: Chronic kidney disease is a major public health problem worldwide. As kidney function declines, it leads to several metabolic abnormalities including dysregulation of mineral metabolism. It is also reported that hyperphosphatemia in patients with advanced kidney disease is associated with an increased risk of mortality and cardiovascular events, and is higher in dialysis-dependent chronic kidney disease (CKD) patients compared to non-dialysis CKD. However, data in the Indian context is limited. Objectives were to evaluate and compare serum phosphorus levels and associated factors in non-dialysis and dialysis CKD patients. Also, the impact of dietary phosphate restriction and the use of phosphate binders on serum phosphorus is analysed. Methods: A cross-sectional study was conducted at a tertiary care hospital in Kolkata, India, with 100 CKD patients: 50 non-dialysis CKD patients and 50 dialysis-dependent CKD patients. Relevant demographic, clinical and laboratory parameters including serum phosphorus, calcium, parathyroid hormone (PTH), alkaline phosphatase, albumin and estimated glomerular filtration rate (eGFR) were collected. Data was analyzed using appropriate statistical tests. Results: Mean serum phosphorus was significantly higher in the dialysis CKD group (6.12±0.34 mg/dl) compared to the non-dialysis CKD group (4.56±0.80 mg/dl). Serum calcium and PTH were also higher while eGFR and albumin were lower in the dialysis CKD group. Serum phosphorus levels increased with advancing CKD stages in the non-dialysis group. Phosphate binder helped phosphorus control in dialysis CKD patients. Conclusions: Our study is in confluence with other reports and dietary phosphate restriction and the use of phosphate binders help optimize phosphorus levels in CKD patients.

Incidence of Fractures after Intravenous Iron: A Retrospective Analysis Comparing Ferric Carboxymaltose and Ferric Derisomaltose

Background: Hypophosphatemia is a frequent side-effect of certain intravenous (i.v.) iron formulations, and a recent meta-analysis of prospective clinical trials reported that 54% of patients treated with ferric carboxymaltose (FCM) develop hypophosphatemia. While the incidence and time-course of hypophosphatemia are well known, the frequency of clinical consequences of these changes is poorly described. FCM infusions cause high intact fibroblast growth factor 23 (iFGF23), which is associated with hypophosphatemia, hyperphosphaturia, hypocalcitriolemia, hypocalcemia, secondary hypoparathyroidism, which is summarized as the ‘6H-syndrome’ that can ultimately result in osteomalacia. The association between treatment with FCM, high iFGF23, osteomalacia with fractures and nephrolithiasis is well documented in multiple case reports. This is not the case for ferric derisomaltose (FDI). Aims: The aim of the present study was to assess the incidence of fractures or radiological signs of osteomalacia and kidney stone in patients treated with FCM or FDI. Methods: Patients treated with FCM or FDI between January 2010 und December 2019 were identified by retrospective assessment of electronic health records of the University Hospital in Innsbruck, which is a large tertiary referral center in Western Austria. Dose, time of infusion, comorbidities and haematological parameters, serum iron parameters as well as markers of mineral metabolism were extracted from the healthcare records of each patient. Radiological and clinical endpoints included fractures, radiological signs of osteomalacia and kidney stone disease after the first infusion of FCM or FDI. The year before the first infusion was used as a control period. Results: In total, 289 patients were included and the median follow-up time was 5.8 years. Mean age was 44.6 years and 184 of 289 patients (64%) were females. In total 179 patients were treated with FCM and 110 patients received FDI. Grouping patients by drug revealed no differences in cumulative iron dose or number of drug applications. At baseline, serum creatinine was significantly lower in FDI-treated patients, but within the normal range for both groups. Mean hemoglobin concentrations were significantly lower in FCM-treated than in FDI-treated patients (95 g/L vs. 109 g/L) with no statistically significant differences in mean ferritin concentrations between groups at baseline. Assessment of treatment response 1-3 months after i.v. iron treatment showed a robust increase in hemoglobin and serum ferritin in both treatment groups. Baseline phosphate was significantly lower in FDI-treated patients with 3.07 mg/dL versus 3.34 mg/dL in the FCM treatment group. In FCM-treated patients a significantly greater change from baseline to 1-3 months after administration was found for phosphorous and calcium (Table 1). Hypophosphatemia was more commonly documented and more severe in FCM-treated patients, who also showed a significant increase in ALP. In a time to event analysis (fracture, osteomalacia and kidney stones) a significantly higher proportion of patients reached the combined endpoint in the FCM treatment group than in FDI-treated patients (Figure 1). Univariate Cox-regression for fractures after the infusion showed a HR of 4.54 for FCM treatment when compared to FDI (p=0.04). In contrast, no difference in fracture incidence was present in the year before the first iron infusion when both treatment groups were compared. Conclusions: In this retrospective analysis the combined event rate of fracture, radiological signs of osteomalacia and kidney stones was significantly higher among patients treated with FCM than after FDI treatment. This finding suggests that the observed changes in markers of mineral metabolism could indicate that FCM treatment is associated with a significantly higher risk of clinically relevant bone complications and kidney stone disease.

The effect of intradialytic exercise on calcium, phosphorus and parathyroid hormone: a randomized controlled trial

BackgroundPatients with kidney failure experience derangements of circulating markers of mineral metabolism and dysregulation of skeletal and cardiovascular physiology which results in high mortality rate in these patients. This study aimed to evaluate the effect of intradialytic exercise on regulation of these abnormalities in patients receiving chronic hemodialysis (HD).MethodsIn this randomized controlled trial conducted in an HD center in Iran, adult patients receiving chronic HD were randomized to intradialytic exercise (60 min) in the second hour of thrice weekly dialysis for 6 months (intervention) or no intradialytic exercise (control). The primary outcomes were serum calcium, serum phosphorous and parathyroid hormone levels. Secondary outcomes were serum alkaline phosphatase and calcium-phosphorous product.ResultsThe study included 44 participants randomized to intervention (n = 22) or control (n = 22). During the 6-month intervention period, significant between-group changes were observed in all primary and secondary outcomes between the intervention and control groups. Statistical analyses reveal a significant increase in serum calcium (P < 0.05) as well as a significant decrease in serum phosphorous, parathyroid hormone, alkaline phosphatase and calcium-phosphorous product (P < 0.05).ConclusionIntradialytic exercise performed for at least 60 min during thrice weekly dialysis sessions improves bone mineral metabolism in adult patients receiving HD. Further studies should focus on observing and comparing the effect of different types of exercise on bone mineral disorders and all-cause mortality in HD patients.Trial registrationClinicalTrials.gov Identifier: NCT04916743, Registered on 08/06/2021. Registered trial name: The Effect of Intradialytic Exercise on Calcium, Phosphorous and Parathyroid Hormone: A Randomized Controlled Trial.

Mineral and Bone Metabolism Markers and Mortality in Diabetic Patients on Haemodialysis.

Diabetic patients on haemodialysis have a higher risk of mortality than non-diabetic patients. The aim of this COSMOS analysis was to assess whether bone and mineral laboratory values (calcium, phosphorus, and PTH) contribute to such risk. COSMOS is a multicentre, open-cohort, 3-year prospective study, which includes 6797 patients from 227 randomly selected dialysis centres from 20 European countries. The association between mortality and calcium, phosphate or PTH was assessed using Cox proportional hazard regression models using both penalized splines smoothing and categorization according to KDIGO guidelines. The effect modification of the association between the relative risk of mortality and serum calcium, phosphate or PTH by diabetes was assessed. There was a statistically significant effect modification of the association between the relative risk of mortality and serum PTH by diabetes (p = 0.011). The slope of the curve of the association between increasing values of PTH and relative risk of mortality was steeper for diabetic compared with non-diabetic patients, mainly for high levels of PTH. In addition, high serum PTH (> 9 times the normal values) was significantly associated with a higher relative risk of mortality in diabetic patients but not in non-diabetic patients (1.53[95%CI:1.07-2.19] and 1.17[95%CI:0.91-1.52]). No significant effect modification of the association between the relative risk of mortality and serum calcium or phosphate by diabetes was found (p = 0.2 and p = 0.059, respectively). The results show a different association of PTH with the relative risk of mortality in diabetic and non-diabetic patients. These findings could have relevant implications for the diagnosis and treatment of CKD-MBD.

Long term reduction of cardiovascular risk factors associated with three hour daily dialysis: A prospective, cohort study.

Daily hemodialysis (DHD) compared to conventional hemodialysis (CHD) leads to improvements in left ventricular hypertrophy and mineral metabolism at 1-year follow-up. However, there is no information from prospective studies on the long terms effects of DHD on these key cardiovascular risk factors. We conducted a 4 year, prospective cohort study of 26 DHD and 51 matched CHD patients on the effect of DHD (six sessions/week × 3 h) versus CHD (three sessions/week × 4 h), 15 DHD, and 26 CHD patients completed 4-years follow-up. Measures of left ventricular mass index (LVMI), blood pressures, hemoglobin, and mineral metabolism markers were performed. Systolic and diastolic blood pressures were significantly lower in the DHD group than the CHD group at 4-year follow-up, 128 mmHg (95% CI, 111-143) versus 148 mmHg (95% CI, 137-158) (p < 0.05) and 60 mmHg (95% CI, 56-63) versus 71 mmHg (95% CI, 64-76) (p < 0.05). DHD was associated with fewer patients taking any anti-hypertensive drug therapy than CHD, 50% versus 80% (p < 0.05). DHD was associated with improved attainment of mineral metabolism goals for phosphorus (adjusted HR 3.6, p = 0.002) and calcium × phosphorus product (adjusted HR 3.66, p = 0.001) at 4-years follow-up compared to CHD. At 4 years, there was a nonsignificant trend toward lower LVMI in the DHD than in the CHD group: 116 g/m2 (95% CI, 97-136) versus 138 g/m2 (95% CI, 115-172) (p = 0.23). Similarly, improvements in hemoglobin also persisted at 4 years follow-up. DHD is associated with long-term (4 year) improvements in key cardiovascular risk factors: blood pressure, mineral metabolism, and anemia with trends toward improved LVMI.

Densitometric justification of the diagnosis of osteoporosis in patients with chronic kidney disease stage 5D

BACKGROUND. Chronic kidney disease leads to increased bone fragility and fractures. Assessing the risk of fractures is a direct way to prevent them. THE AIM: to assess the possibility of using DXA to predict fracture risk in patients with stage 5D CKD. PATIENTS AND METHODS. The prospective cohort study included 359 patients (166 men, 193 women). BMD was evaluated by DRA. Some markers of mineral and bone metabolism were also analyzed. All fractures in patients were recorded from the moment of inclusion in the study. RESULTS. All patients with fractures had lower BMD and received longer-term renal replacement therapy (RRT). The absolute risk of fractures increased as BMD decreased. Patients with fractures had higher levels of parathyroid hormone and alkaline phosphatase. Stepwise multivariate regression analysis showed that the combination of BMD scores of the forearm, hip, lumbar vertebrae and the duration of RRT best predicts the risk of fractures. The presence of previous fractures also increases risk for the future. Risk of fractures in man and women did not differ. CONCLUSION. The risk of fractures in patients with CKD 5 st. on maintenance hemodialysis increases with a decrease in BMD, an increase in the duration of RRT and the presence of previous fractures, but does not significantly depends on the gender of the patients. It is also can be concluded that it is possible to use criteria reflecting the state of BMD, taking into account their sensitivity and specificity, in assessing the risk of fractures in patients with CKD 5D st.

Changes in individual diagnostic markers of carbohydrate, lipid and mineral metabolism in dairy cows due to feeding

Relevance. Any changes in the functional processes in the body of cows are reflected in the biochemical parameters of their blood. In highly productive animals, the energy costs in the postpartum period for the formation of lactation are not covered by the volume of feed consumed. The lack of energy is compensated by the internal reserves of the body, which causes the catabolic nature of metabolism. The consequence of a violation of protein, carbohydrate-fat and vitamin-mineral metabolism in general is a change in the hormonal status of the body, which negatively affects the reproductive function and leads to a decrease in milk productivity.Methods. The formation of animal groups and methodological techniques for setting scientific and economic experience were performed according to A. Ovsyannikov. The diets, the composition of the premix and the tested feed additive are designed using the program «Optima expert» («Cormersurs», Russia) the needs of milking cows in nutrient and biologically active substances were determined by A. Kalashnikov, V. Fisinin, V. Shcheglov and others. In the blood serum, the content, glucose, cholesterol, triglycerides, general calcium, and the unorganic focoria on the semi-automatic biochemical analyzer with the BS-3000M cuvette were determined. The results were processed biometrically, the reliability of the differences was evaluated by the Students t-criterion.Results. The maximum increase in the concentration of glucose in the blood was observed in cows of the third group (7.93%) (p &lt; 0.05), cholesterol – in cows of the second group (24.43%). The content of triglycerides in animals of the control group decreased by 25.00% (p &lt; 0.05). The level of calcium in the blood serum of animals was a tendency to increase. The most pronounced increase was observed in individuals of the third group. In animals of experimental groups, the level of fosphor inorganic decreased.

Markers of Kidney Tubular Function Deteriorate While Those of Kidney Tubule Health Improve in Primary Aldosteronism After Targeted Treatments.

Background Targeted treatment with mineralocorticoid receptor antagonists (MRAs) or adrenalectomy in patients with primary aldosteronism (PA) causes a decline in estimated glomerular filtration rate; however, the associated simultaneous changes in biomarkers of kidney tubule health still remain unclear. Methods and Results We matched 104 patients with newly diagnosed unilateral PA who underwent adrenalectomy with 104 patients with unilateral PA who were treated with MRAs, 104 patients with bilateral PA treated with MRAs, and 104 patients with essential hypertension who served as controls. Functional biomarkers were measured before the targeted treatment and 1 year after treatment, including serum markers of kidney function (cystatin C, creatinine), urinary markers of proximal renal tubular damage (L-FABP [liver-type fatty-acid binding protein], KIM-1 [kidney injury molecule-1]), serum markers of kidney tubular reserve and mineral metabolism (intact parathyroid hormone), and proteinuria. Compared with the patients with essential hypertension, the patients with PA had higher pretreatment serum intact parathyroid hormone and urinary creatinine-corrected parameters, including L-FABP, KIM-1, and albumin. The patients with essential hypertension and with PA had similar cystatin C levels. After treatment with MRAs or adrenalectomy of unilateral PA and MRAs of bilateral PA, the patients with PA had increased serum cystatin C and decreased urinary L-FABP/creatinine, KIM-1/creatinine, creatinine-based estimated glomerular filtration rate, intact parathyroid hormone, and proteinuria (all P<0.05). In multivariable regression models, a higher urinary L-FABP/creatinine ratio and older age were significantly correlated with the occurrence of kidney failure (estimated glomerular filtration rate dip ≥30%) in the patients with PA after targeted treatment. Conclusions Compared with the matched patients with essential hypertension, the incident patients with PA at diagnosis had higher levels of several biomarkers, including markers of kidney damage, tubular reserve/mineral metabolism, and proteinuria. Functional kidney failure in the patients with PA after treatment could be predicted by a higher baseline urinary L-FABP/creatinine ratio and older age. After targeted treatments in the patients with bilateral or unilateral PA, these biomarkers of kidney tubule health were restored, but creatinine-based estimated glomerular filtration rate declined, which may therefore reflect hemodynamic changes rather than intrinsic damage to kidney tubular cells.

Quantitative assessment of lumbar spine bone marrow in patients with different severity of CKD by IDEAL-IQ magnetic resonance sequence.

BackgroundChronic kidney disease (CKD) has a significant negative impact on bone health. Bone marrow is an essential component of bone, mainly composed of trabecular bone and fat. The IDEAL-IQ sequence of MRI allows indirect quantification of trabecular bone mass by R2* and direct quantification of bone marrow fat content by FF map, respectively.ObjectiveOur objective was to explore the association of CKD severity with bone marrow using IDEAL-IQ and whether mineral and bone metabolism markers alter this association.MethodWe recruited 68 CKD patients in this cross-sectional research (15 with CKD stages 3-4, 26 with stage 5, and 27 with stage 5d). All patients underwent lumbar spine IDEAL-IQ, BMD, and several bone metabolism markers (iPTH, 25-(OH)-VitD, calcium and phosphorus). Multiple linear regression analysis was used to examine the association of CKD severity with MRI measurements (R2* and FF).ResultsMore severe CKD was associated with a higher R2* value [CKD 5d versus 3-4: 30.077 s-1 (95% CI: 12.937, 47.217), P for trend < 0.001], and this association was attenuated when iPTH was introduced [CKD 5d versus 3-4: 19.660 s-1 (95% CI: 0.205, 39.114), P for trend = 0.042]. Furthermore, iPTH had an association with R2* value [iPTH (pg/mL): 0.033 s-1 (95% CI: 0.001, 0.064), P = 0.041]. Besides, FF was mainly affected by age and BMI, but not CKD.ConclusionsThe bone marrow R2* value measured by IDEAL-IQ sequence is associated with CKD severity and iPTH. The R2* of IDEAL-IQ has the potential to reflect lumbar bone changes in patients with CKD.

Mineral and bone metabolism in patients with idiopathic scoliosis depending on the magnitude of the deformity

Objective: Analysis of the results of the study of mineral metabolism and bone formation markers in patients with idiopathic scoliosis, depending on the magnitude of the deformity.Material and methods: Based on the retrospective single‑center study in 30 patients diagnosed with scoliosis the preoperative parameters of calcium metabolism (total and ionized calcium, parathyroid hormone, 24‑hour urine calcium), phosphorus, bone formation markers (alkaline phosphatase, osteocalcin, P1NP in the blood), deoxypyridinoline in morning urine, blood levels of 25(OH)D have been analyzed. The patients were divided into 3 groups: with a deformity of 25–40 ° (group 1), 40–60 ° (group 2) and 60–80 ° (group 3) (n = 30). The mean age in all groups was 18.5 ± 4.7.Results: In patients with idiopathic scoliosis, alkaline phosphatase and P1NP significantly exceeded normal values in the first group, which indicated a more high‑turnover type of bone remodeling with a deficient level of 25(OH)D. A higher excretion of deoxypyridinoline and a decrease in phosphorus in blood in patients with a deformity of 60–80 ° suggest a violation of the ratio of the processes of synthesis and resorption in bone tissue.Conclusion: The study of mineral metabolism and all the main markers of bone formation made it possible to obtain a more complete picture of the state of metabolic processes in bone tissue, to obtain reliable data on the effect of some of them on the nature of bone remodeling and the magnitude of spinal deformity.

Simultaneous assessment of microcalcifications and morphological criteria of vulnerability in carotid artery plaque using hybrid 18F-NaF PET/MRI

BackgroundPrevious studies have suggested the role of microcalcifications in plaque vulnerability. This exploratory study sought to assess the potential of hybrid positron-emission tomography (PET)/magnetic resonance imaging (MRI) using 18F-sodium fluoride (18F-NaF) to check simultaneously 18F-NaF uptake, a marker of microcalcifications, and morphological criteria of vulnerability. Methods and resultsWe included 12 patients with either recently symptomatic or asymptomatic carotid stenosis. All patients underwent 18F-NaF PET/MRI. 18F-NaF target-to-background ratio (TBR) was measured in culprit and nonculprit (including contralateral plaques of symptomatic patients) plaques as well as in other arterial walls. Morphological criteria of vulnerability were assessed on MRI. Mineral metabolism markers were also collected. 18F-NaF uptake was higher in culprit compared to nonculprit plaques (median TBR 2.6 [2.2-2.8] vs 1.7 [1.3-2.2]; P = 0.03) but was not associated with morphological criteria of vulnerability on MRI. We found a positive correlation between 18F-NaF uptake and calcium plaque volume and ratio but not with circulating tissue-nonspecific alkaline phosphatase (TNAP) activity and inorganic pyrophosphate (PPi) levels. 18F-NaF uptake in the other arterial walls did not differ between symptomatic and asymptomatic patients. Conclusions18F-NaF PET/MRI may be a promising tool for providing additional insights into the plaque vulnerability.

Genetic Variants Associated With Mineral Metabolism Traits in Chronic Kidney Disease.

Chronic kidney disease (CKD) causes multiple interrelated disturbances in mineral metabolism. Genetic studies in the general population have identified common genetic variants associated with circulating phosphate, calcium, parathyroid hormone (PTH), and fibroblast growth factor 23 (FGF23). In this study we aimed to discover genetic variants associated with circulating mineral markers in CKD. We conducted candidate single-nucleotide variation (SNV) analysis in 3027 participants in the multiethnic Chronic Renal Insufficiency Cohort (CRIC) to determine the associations between SNVs and circulating levels of mineral markers. SNVs adjacent to or within genes encoding the regulator of G protein-coupled signaling 14 (RGS14) and the calcium-sensing receptor (CASR) were associated with levels of mineral metabolites. The strongest associations (P < .001) were at rs4074995 (RGS14) for phosphate (0.09 mg/dL lower per minor allele) and FGF23 (8.6% lower), and at rs1801725 (CASR) for calcium (0.12 mg/dL higher). In addition, the prevalence of hyperparathyroidism differed by rs4074995 (RGS14) genotype (chi-square P < .0001). Differential inheritance by race was noted for the minor allele of RGS14. Expression quantitative loci (eQTL) analysis showed that rs4074995 was associated with lower RGS14 gene expression in glomeruli (P = 1.03 × 10-11) and tubules (P = 4.0 × 10-4). We evaluated genetic variants associated with mineral metabolism markers in a CKD population. Participants with CKD and the minor allele of rs4074995 (RGS14) had lower phosphorus, lower plasma FGF23, and lower prevalence of hyperparathyroidism. The minor allele of RGS14 was also associated with lower gene expression in the kidney. Further studies are needed to elucidate the effect of rs4074995 on the pathogenesis of disordered mineral metabolism in CKD.

MO540: Are the Haematological Markers of Inflammation Predictors of Fibroblast Growth Factor-23 in Non-Dialysis Chronic Kidney Disease?

Abstract BACKGROUND AND AIMS Recently, a growing body of evidence point to the relationships between inflammation and fibroblast growth factor 23 (FGF23) in adults with and without chronic kidney disease (CKD). On the other hand, some haematological indices derived from the complete blood count appear as simple and inexpensive biomarkers of systemic inflammation. Therefore, this study aimed to evaluate the association between the haematological markers of inflammation and FGF23 in non-dialysis CKD. METHOD This single centre, cross-sectional study prospectively enrolled 90 subjects with moderate to severe stable CKD [median estimated glomerular filtration rate (eGFR) 25 (95% confidence interval 95% CI 24.9–30.5) mL/min, 46% in stage G3, urinary albumin-to-creatinine ratio (ACR) 221 (95% CI 498–954) mg/g], mostly males (61%), aged 62 (95% CI 57–64) years. Patients on renal replacement therapy (RRT) and those with active malignancies, infectious and inflammatory diseases were excluded. Demographic, past medical history (CKD vintage and etiology, comorbidities, chronic medications) and laboratory data were collected. Haematological markers of systemic inflammation [red blood cell distribution width (RDW), platelet distribution width (PDW), neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR)] were obtained from the complete blood count. Other measured lab parameters were: c-terminal FGF23 (cFGF23), intact parathyroid hormone (iPTH), serum calcidiol (25OHD), total calcium (tCa), phosphate (PO4), alkaline phosphatase, C-reactive protein, albumin, transferrin, ferritin and transferrin saturation, as markers of mineral metabolism, inflammatory, nutritional and iron status, respectively. Associations among studied parameters were assessed by Spearman rank test, multivariate linear regression and logistic regression models. Non-parametric variables were log-transformed. RESULTS The median cFGF23 was 4.65 (95% CI 7.57–14.4) pg/mL. Subjects in the highest cFGF23 quartile [n = 22, cFGF23 20.8 (95% CI 20.8–40.8) pg/mL] had higher RDW (P = 0.02), iPTH (P &amp;lt; 0.001), PO4 (P = 0.005) and ACR (P = 0.004), but lower tCa (P = 0.04), haemoglobin (P = 0.01) and eGFR (P &amp;lt; 0.001) as compared to those in the lowest quartile [n = 23, cFGF23 0.84 (95% CI 0.71–1.10) pg/mL]. Moreover, they had higher proportions of arterial hypertension (P = 0.01) and previous treatment with intravenous iron (P = 0.03). A trend to higher PLR (P = 0.052), NLR (P = 0.064), and ferritin (P = 0.076) was also observed. However, beside the expected bivariate correlations with eGFR, ACR, iPTH, tCa and PO4, cFGF23 was further correlated solely with haemoglobin (rs = –0.33, P = 0.002). In a multivariate linear regression model which explained 34% of the log(cFGF23) variance, log(PLR) (B 1.59, 95% CI 0.14–3.03, P = 0.03) and log(eGFR) (B –1.65, 95% CI –2.51 to –0.80, P &amp;lt; 0.001) were independent predictors. After adjustment for history of arterial hypertension and previous intravenous iron treatment, in a model of logistic regression (Nagelkerke R2 0.57, Chi2 16.7, P = 0.03), log(eGFR) was found as independent predictor of the log(FGF23) [odds ratio (OR) 0.07, 95% CI 0.01–0.36, P = 0.002]. However, RDW was retained in the last step of this model with a borderline significance (OR 4.3, 95% CI 0.98–19.02, P = 0.052). CONCLUSION Taken together, our findings suggest that, in addition to the kidney function, RDW and PLR seem to predict cFGF23 in non-inflammed, stable, non-dialysis CKD adults. Thus, one might speculate in favour of the association between chronic inflammatory state and FGF23 metabolism and in support of the revelatory role of some haematological markers of inflammation, a hypothesis that needs further research.

MO451: The Usefulness of Calcium/Magnesium Ratio in the Risk Stratification of Early Onset of Renal Replacement Therapy

Abstract BACKGROUND AND AIMS Recently, a growing number of studies have reported a close relationship between high serum calcium and low serum magnesium with vascular calcification. Endothelial dysfunction and vascular inflammation seem plausible risk factors for enhanced progression of kidney disease nevertheless, the knowledge remains scarce. The aim of this study is to evaluate the role of the calcium/magnesium ratio as a risk factor in CKD progression. METHOD Observational, prospective study involving 693 patients (f = 371, m = 322) with stage 4 and 5 CKD. Patients were divided into two groups, according to the development of end-stage renal disease (ESRD): G1 (n = 541), who did not undergo renal replacement therapy and G2 (n = 152), who had started renal replacement therapy (RRT). Several laboratory parameters were measured: haemoglobin, eGFR (MDRD), albumin, cholesterol, magnesium and mineral metabolism markers (PTH, calcium and phosphorus). Baseline characteristics were analysed and compared using Student%u2019s T-test for continuous variables and chi-squared test for categorical variables. Multivariate Cox regression analysis was used to identify independent factors associated with RRT initiation. A modified Poisson regression with robust error variance was used to estimate the cumulative relative risk for RRT initiation. RESULTS The mean age and estimated glomerular filtration rate (eGFR) of the study population was 70.09 ± 12.51 years and 19.91 ± 8.11 mL/min, respectively. Comparing the two groups, G2 had a significantly lower serum levels of Hb (11.75 versus 10.95 g/dL, P = 0.000), calcium (9.34 versus 8.95 mg/dL, P = 0.000), magnesium (1.92 versus 1.40 mg/dL, P = 0.0001), albumin (4.00 versus 3.88 g/dL, P = 0.03) and cholesterol (183.17 versus 172.39 mg/dL, P = 0.01) and a higher serum levels of phosphorus (3.88 versus 4.69 mg/dL, P = 0.0001), calcium/magnesium ratio (5.73 versus 7.56, P = 0.0001) and PTH (209.71 versus 338.84 pg/mL, P = 0.0001). In univariate Cox regression analysis, age, haemoglobin, eGFR, calcium, magnesium, phosphorus, calcium-magnesium ratio and PTH correlate with onset of RRT, which were further tested using a multivariate COX regression model. The results showed a clear relationship between high levels of phosphorus (HRa = 1.638, P = 0.001) and calcium-magnesium ratio (HRa = 1.292; P = 0.002), and low levels of magnesium (HRa = 0.761, P = 0.005) and eGFR (HRa = 0.934; P = 0.0001) were independent risk factors to start depurative techniques. Additionally, Poisson regression analysis showed that high calcium-magnesium ratios (aPR = 1.986; 95% CI 1.026–3.051; P = 0.002), high phosphorus levels (aPR = 1.607; 95% CI 1.324–1.950; P &amp;lt; 0.0001) and low levels eGFR (aPR = 0.927; 95% CI 0.891–0.964; P &amp;lt; 0.0001) were associated with a cumulative risk for initiation of RRT. CONCLUSION Our results suggest that the calcium/magnesium ratio is an independent predictive factor for the initiation of renal replacement therapy. Further studies are required to validate the use of this novel marker as a predictor of CKD progression.

Bone phenotypes in multiple endocrine neoplasia type 1: survey on the MEN1 Florentine database.

Multiple endocrine neoplasia type 1 (MEN1) is a rare, inherited cancer syndrome characterized by the development of multiple endocrine and non-endocrine tumors. MEN1 patients show a reduction of bone mass and a higher prevalence of early onset osteoporosis, compared to healthy population of the same age, gender, and ethnicity. During the monitoring and follow-up of MEN1 patients, the attention of clinicians is primarily focused on the diagnosis and therapy of tumors, while the assessment of bone health and mineral metabolism is, in many cases, marginally considered. In this study, we retrospectively analyzed bone and mineral metabolism features in a series of MEN1 patients from the MEN1 Florentine database. Biochemical markers of bone and mineral metabolism and densitometric parameters of bone mass were retrieved from the database and were analyzed based on age ranges and genders of patients and presence/absence of the three main MEN1-related endocrine tumor types. Our evaluation confirmed that patients with a MEN1 diagnosis have a high prevalence of earlyonset osteopenia and osteoporosis, in association with levels of serum and urinary markers of bone turnover higher than the normal reference values, regardless of their different MEN1 tumors. Fifty percent of patients younger than 26 years manifested osteopenia and 8.3% had osteoporosis, in at least one of the measured bone sites. These data suggest the importance of including biochemical and instrumental monitoring of bone metabolism and bone mass in the routine medical evaluation and follow-up of MEN1 patients and MEN1 carriers as important clinical aspects in the management of the syndrome.

Gla-Rich Protein, Magnesium and Phosphate Associate with Mitral and Aortic Valves Calcification in Diabetic Patients with Moderate CKD.

Accelerated and premature cardiovascular calcification is a hallmark of chronic kidney disease (CKD) patients. Valvular calcification (VC) is a critical indicator of cardiovascular disease and all-cause mortality in this population, lacking validated biomarkers for early diagnosis. Gla-rich protein (GRP) is a cardiovascular calcification inhibitor recently associated with vascular calcification, pulse pressure, mineral metabolism markers and kidney function. Here, we examined the association between GRP serum levels and mitral and aortic valves calcification in a cohort of 80 diabetic patients with CKD stages 2–4. Mitral and aortic valves calcification were detected in 36.2% and 34.4% of the patients and associated with lower GRP levels, even after adjustments for age and gender. In this pilot study, univariate, multivariate and Poisson regression analysis, show that low levels of GRP and magnesium (Mg), and high levels of phosphate (P) are associated with mitral and aortic valves calcification. Receiver operating characteristic (ROC) curves showed that the area under the curve (AUC) values of GRP for mitral (0.762) and aortic (0.802) valves calcification were higher than those of Mg and P. These results suggest that low levels of GRP and Mg, and high levels of P, are independent and cumulative risk factors for VC in this population; the GRP diagnostic value might be potentially useful in cardiovascular risk assessment.

A novel long-term intravenous combined with local treatment with human amnion-derived mesenchymal stem cells for a multidisciplinary rescued uremic calciphylaxis patient and the underlying mechanism.

Calciphylaxis is a rare disease characterized histologically by microvessel calcification and microthrombosis, with high mortality and no proven therapy. Here, we reported a severe uremic calciphylaxis patient with progressive skin ischemia, large areas of painful malodorous ulcers, and mummified legs. Because of the worsening symptoms and signs refractory to conventional therapies, treatment with human amnion-derived mesenchymal stem cells (hAMSCs) was approved. Preclinical release inspections of hAMSCs, efficacy, and safety assessment, including cytokine secretory ability, immunocompetence, tumorigenicity, and genetics analysis in vitro, were introduced. We further performed acute and long-term hAMSC toxicity evaluations in C57BL/6 mice and rats, abnormal immune response tests in C57BL/6 mice, and tumorigenicity tests in neonatal Balbc-nu nude mice. After the preclinical research, the patient was treated with hAMSCs by intravenous and local intramuscular injection and external supernatant application to the ulcers. When followed up to 15 months, the blood-based markers of bone and mineral metabolism improved, with skin soft tissue regeneration and a more favorable profile of peripheral blood mononuclear cells. Skin biopsy after 1-month treatment showed vascular regeneration with mature noncalcified vessels within the dermis, and 20 months later, the re-epithelialization restored the integrity of the damaged site. No infusion or local treatment-related adverse events occurred. Thus, this novel long-term intravenous combined with local treatment with hAMSCs warrants further investigation as a potential regenerative treatment for uremic calciphylaxis due to effects of inhibiting vascular calcification, stimulating angiogenesis and myogenesis, anti-inflammatory and immune modulation, multidifferentiation, re-epithelialization, and restoration of integrity.