Alkaline Phosphatase Levels In Patients Research Articles

Assessment of Testosterone Levels, Kidney Function and Alkaline Phosphatase in Patients with Benign Prostatic Enlargement in Kirkuk City/Iraq

The present study is designed to evaluate the concentration of Testosterone, Creatinine, Urea urea, and alkaline phosphatase levels in patients with benign prostatic hyperplasia. This study was conducted for the period from the beginning of October 2023 to the end of February 2024 at Kirkuk Hospital. General and specialized medical clinics in the city of Kirkuk. The study included (70) males with benign prostatic hyperplasia, ages (45-75) years, and average weight (82) kg. In addition to 20 samples of healthy people with the same rate of ages and weights of patients, study samples were distributed as follows: The first group: the control group and included (20) healthy males, and the second group: the patient group and distributed to three groups according to the age groups first category ( 45-55) years and included 25 patients, the second age group (56-65) years and included 20 patients, the third age group (66-75) years and included 25 patients. The results of the current study showed a significant increase (p ≤ 0.05) in the concentration of urea, creatinine and alkaline phosphatase enzyme in patients with benign prostatic hyperplasia compared to healthy people, and the current study showed a significant decrease (P ≤ 0.05) in testosterone concentration in patients with benign prostatic hyperplasia compared to healthy people. According to age groups, the results showed no significant differences (p ≤ 0.05) in the concentrations of urea, creatinine and alkaline phosphatase enzyme in patients with prostatic hyperplasia, and the results showed a significant decrease (p≤ 0.05) in the concentration of testosterone according to the age groups of patients with benign prostatic hyperplasia.

A retrospective study: analysis of the relationship between lactate dehydrogenase and castration-resistant prostate cancer based on restricted cubic spline model.

Different prostate cancer patients take different amounts of time to progress to castration-resistant prostate cancer (CRPC), and this difference in time determines the patient's ultimate survival time. If the time to progression to CRPC can be estimated for each patient, the treatment can be better individualized. Castration-resistant prostate cancer is a challenge in attacking prostate cancer, the aim of the paper is to analyze the correlation between lactate dehydrogenase (LDH) and CRPC occurrence based on the restricted cubic spline model, and to provide a theoretical basis for LDH as a prognostic biomarker for prostate cancer patients. We retrospectively analyzed clinical and follow-up data of patients diagnosed with prostate cancer and treated with Androgen Deprivation Therapy (ADT) in our hospital from October 2019 to August 2022. Investigate the correlation between LDH and CRPC by COX regression, restricted cubic spline model and survival analysis. The initial tPSA concentration, prostate volume, LDH and alkaline phosphatase levels in patients with prostate cancer with rapid progression are higher than those in patients with prostate cancer with slow progression. Multivariate COX regression showed that initial tPSA level and LDH level are independent risk factors for prostate cancer. Restricted cubic spline model further showed that LDH level is linearly correlated with the risk of CRPC in prostate cancer patients (total P<0.05, nonlinear P>0.05). LDH was associated with the prognosis of prostate cancer and had a dose-response relationship with the risk of CRPC in prostate caner patients.

Ursodeoxycholic Acid Use After Bariatric Surgery: Effects on Metabolic and Inflammatory Blood Markers

BackgroundIn addition to the reduction of symptomatic gallstone disease, ursodeoxycholic acid (UDCA) might also have beneficial metabolic effects after bariatric surgery. We examined the impact of UDCA on liver enzymes, hemoglobin A1c (HbA1c), lipids, and inflammation markers.MethodsPatients in the UPGRADE trial (placebo-controlled, double-blind) were randomized between UDCA 900 mg daily or placebo pills for 6 months after bariatric surgery. Patients without blood measurements pre- or 6 months postoperatively were excluded. The change in liver enzymes, Hba1c, lipids, and inflammation markers after surgery were compared between the UDCA and placebo group, followed by a postoperative cross-sectional comparison.ResultsIn total, 513 patients were included (age [mean ± SD] 45.6 ± 10.7 years; 79% female). Preoperative blood values did not differ between UDCA (n = 266) and placebo (n = 247) groups. Increase of alkaline phosphatase (ALP) was greater in the UDCA group (mean difference 3.81 U/l [95%CI 0.50 7.12]). Change in other liver enzymes, HbA1c, lipids, and CRP levels did not differ. Postoperative cross-sectional comparison in 316 adherent patients also revealed a higher total cholesterol (mean difference 0.25 mg/dl [95%CI 0.07–0.42]), lower aspartate aminotransferase (mean difference −3.12 U/l [−5.16 – −1.08]), and lower alanine aminotransferase level (mean difference −5.89 U/l [−9.41 – −2.37]) in the UDCA group.ConclusionUDCA treatment leads to a higher, but clinically irrelevant increase in ALP level in patients 6 months after bariatric surgery. No other changes in metabolic or inflammatory markers were observed. Except for the reduction of gallstone formation, UDCA has no effects after bariatric surgery.Graphical

CHILDREN ON ANTI EPILEPTIC DRUGS HAVE LOW SERUM CALCIUM AND RAISED ALKALINE PHOSPHATASE LEVELS

Objective: Epilepsy is a common neurological disorder in children requiring long-term therapy using anti-epileptic drugs (AEDs). Chronic use of AEDs may impair bone health. This study aimed to determine the biochemical changes affecting bone metabolism in pediatric epileptic patients taking AEDs. Materials and Methods: This cross-sectional study was conducted in the Department of Pediatrics of Benazir Bhutto Hospital, Rawalpindi from January 2019 to July 2019. A total of 95 children were enrolled based on non-probability consecutive sampling technique. Bone metabolism was evaluated by measuring serum calcium and alkaline phosphatase levels in all the study participants. Data was entered on SPSS v 22 and descriptive statistics were applied. Results: Of 95 epileptic children, 50.53% (n=48) were male and 49.47% (n=47) were females taking AEDs (either carbamazepine, valproate sodium or phenobarbital), 47.37% (n=45) were between 2-6 years of age while 52.63% (n=50) were between 7-11 years of age (Mean age: 6.53±2.54 years). Mean calcium and alkaline phosphatase levels of patients were calculated as 7.94±2.3 mg/dl and 226.31±17.45 IU/L respectively. Frequency of hypocalcemia in patients taking AEDs was recorded in 67.37% (n=64) and 81.05% (n=77) had raised alkaline phosphatase levels. Conclusion: This study concludes that frequency of hypocalcemia and raised alkaline phosphatase levels in patients taking AEDs is higher and needs attention to address this issue while the magnitude recorded in this study is primary in local population which needs to be re-assessed through multi-center trials.

Alkaline Phosphatase is an Independent Risk Factor for Periprosthetic Fractures in Total Joint Arthroplasty.

Serum alkaline phosphatase (ALP) is a biomarker for chronic low-grade inflammation along with hepatobiliary and bone disorders. High abnormal ALP levels in blood have been associated with metabolic bone disease and high bone turnover. All primary total hip and knee arthroplasties from 2005 to 2019 were queried from the National Surgical Quality Improvement Program database. Patients with available serum ALP levels were included and stratified to low (<44 IU/L), normal (44 to 147 IU/L), and high (>147 IU/L). A risk-adjusted multivariate logistic regression was used to analyze ALP as an independent risk factor of complications. The analysis included 324,592 patients, consisting of 11,427 low ALP, 305,977 normal ALP, and 7,188 high preoperative ALP level patients undergoing total joint arthroplasty. Adjusted multivariate logistic regression analysis showed high ALP level patients had an overall increased risk of readmission within 30 days of surgery compared with the control group (odds ratio [OR], 1.69; P < 0.01). High ALP patients also had an increased risk of postoperative periprosthetic fracture (OR, 1.6), postoperative wound infection (OR, 1.81), pneumonia (OR, 2.24), renal insufficiency (OR, 2.39), cerebrovascular disease (OR, 2.2), postoperative bleeding requiring transfusion (OR, 1.83), sepsis (OR, 2.35), length of stay > 2 days (OR, 1.47), Clostridium difficile infection (OR, 2.07), and discharge to a rehab facility (OR, 1.41) (all P < 0.05). A low ALP level was also associated with increased postoperative bleeding transfusion risk (OR, 1.12; P < 0.01) and developing a deep vein thrombosis (OR, 1.25; P = 0.03). Abnormal serum ALP levels in patients undergoing primary total joint arthroplasty are associated with increased postoperative periprosthetic fracture risk and medical complications requiring increased length of stay and discharge to a rehabilitation facility.

Correlation between eosinophil count and total protein and alkaline phosphatase in asymptomatic patients with normal and high levels of aspartate aminotransferase from a polyclinic in Villa El Salvador, Lima, Peru

Objective: To evaluate the correlation between eosinophil differential count and total protein and alkaline phosphatase levels in patients with normal and high levels of aspartate aminotransferase from a polyclinic in the district of Villa El Salvador in Lima, Peru. Materials and methods: An observational, analytical and correlational study conducted with apparently healthy male and female patients aged 18 years or older, showing normal and high levels of enzyme aspartate aminotransferase. The study included 279 patients who met the eligibility criteria. Spearman's correlation coefficient was used to determine the correlation between eosinophil count and alkaline phosphatase and total protein in patients with normal and high levels of aspartate aminotransferase. Results: No correlation was found between the variables studied in the group with normal levels of aminotransferases. However, in the group with high levels of aspartate aminotransferase, a moderate and negative correlation was found between eosinophil count and total protein (Rho = -465) and a low and positive correlation between eosinophil count and alkaline phosphatase (Rho = 296). Conclusions: In the presence of aminotransferase levels above the normal range, eosinophils correlate with total protein and alkaline phosphatase. Further studies with a larger number of patients and greater methodological complexity are necessary to determine if the interaction between eosinophils and albumin and phosphatase is frequently seen with high levels of aminotransferases. Moreover, they are necessary to consider possible implications in the pathophysiology of chronic diseases associated with this enzyme, as well as possible clinical and therapeutic implications.

S1262 Alkaline Phosphatase Responsiveness to Ursodiol Therapy in Patients With Primary Biliary Cholangitis and Varying Degrees of Liver Fibrosis

Introduction: Primary biliary cholangitis (PBC) is an inflammatory cholestatic liver disease that destroys the bile duct. PBC is frequently associated with varying degrees of liver fibrosis measured by fibroscan. Various mechanisms such as inflammation, cytokine signaling, and abnormal interaction amongst cholangiocytes and mesenchymal cells contribute to the development of fibrosis. Firstline treatment is ursodiol (UDCA) therapy. This study aims to elucidate the consequences of liver fibrosis on the effectiveness of UDCA therapy indicated by alkaline phosphatase (ALP) levels in PBC patients. Methods: At a single academic center, a retrospective review was conducted to obtain ALP levels in patients with PBC at the start of UDCA therapy and at 6 and 12 month periods. Degree of liver fibrosis determined by fibroscan was recorded. Patients were categorically separated into the following groups: mild (< 8 kPa), moderate (8-14 kPa), and severe ( >14 kPa). Variables were analyzed by chi-squared tests and general linear regression analysis. Results: In 47 PBC patients treated only with UDCA, the mean age was 59.3 years old (range 30-85). 78.7% (n=37) of the patients were females. The mean liver stiffness as per fibroscans was 9.7 kPa (range 3.0-41.5) with a SD of 6.65. The 3 and 5 year survival were both 100% (n=47). 48.9% (n=23) of patients had mild fibrosis, 36.2% (n=17) of patients had moderate fibrosis, and 14.9% (n=7) of patients had severe fibrosis. Regarding patients with mild fibrosis, ALP < 200 at baseline and at 6 and 12 months was 47.8%, 65.2%, and 78.3%, respectively. Regarding patients with moderate fibrosis, ALP < 200 at baseline and at 6 and 12 months was 41.2%, 70.6%, and 70.6%, respectively. Regarding patients with severe fibrosis, ALP < 200 at baseline and at 6 and 12 months was 28.6%, 34.8%, and 100%, respectively. The results of the chi-square test showed no significant association between ALP >200 and categorical liver fibrosis at 6 and 12 months. Linear regression analysis showed no significant liver fibrosis effect on change in ALP >200 from baseline to 6 and 12 months. Conclusion: The number of patients with ALP < 200 across all fibrosis groups increased with UDCA therapy at 6 and 12 months compared to baseline. Based on our results, varying degrees of liver fibrosis do not appear to alter the effectiveness of UDCA in PBC patients. If ALP remains >200 after 12 months of UDCA therapy, additional therapeutics should be considered.

Interleukin -17, Interleukin-23 and Alkalinephosphatase Levels in Patients with Helicobacter pylori Infection

The study was carried out to detection of H.pylori in (218) patients who attended two teaching hospitals in Baghdad. The diagnosis is done by Immunochromatography methods. Stools and blood samples were taken from each patient as well as other (30) healthy control matching in age. The study included measurement the Levels of Interleukin-17, Interleukin-23, and Alkaline phosphatase in sera of patients and control .The result indicated presence of H pylori antigen in 115 cases 59 cases of males and 51 of females , Also, the result indicated increasing levels of IL-17 and IL-23 and Alkaline phosphatase in patients sera in comparison with healthy control.

Segmented linear correlations between bone scan index and prostate cancer biomarkers, alkaline phosphatase, and prostate specific antigen in patients with a Gleason score ≥7.

Technetium-99m methyl diphosphonate bone scintigraphy is relatively easily accessible for detecting bone metastases in prostate cancer patients. However, it is subjective and can be challenging to compare images taken at different time points. The bone scan index (BSI) is a more objective evaluation and allows for better comparison of images. Its correlation with other biomarkers of prostate cancer metastases such as prostate specific antigen (PSA) and alkaline phosphatase (ALP) is not clearly understood. This study thus aimed to compare the BSI correlation to PSA against that of BSI to ALP levels in patients with a Gleason score ≥7.A retrospective analysis of the medical records of 50 prostate cancer patients with a Gleason score of ≥7 referred for a bone scan between January 1, 2015 and December 31, 2018 was undertaken. Bone scans were interpreted visually, and using a semi-automated computer programme to quantify the BSI and its relation to PSA and ALP measurements.For the metastasis positive measurements, there was a statistically significant moderate positive overall linear correlation between BSI and PSA. For ALP and BSI, there were 2 segmented strong positive linear relationships between them. The first segment consisted of ALP < 375 IU/L and BSI >10%, where ALP and BSI were strongly and positively correlated. The other segment tended to have generally low BSI measurements (<10%) and also had a strong and positive correlation.The BSI was found to be better linearly correlated with ALP than PSA.

Serum Alkaline Phosphatase in Cryptogenic Stroke Cases with Active Cancer.

Objective We assessed the relationship between the levels of serum alkaline phosphatase, which is often increased with biliary obstruction and bone metastasis, and active cancer in patients with cryptogenic stroke. Methods Serum alkaline phosphatase levels in patients with cryptogenic stroke sampled upon admission were measured using the Japan Society of Clinical Chemistry method used in Japan. Active cancer was defined as a new diagnosis, treatment, progression, or recurrence within six months before admission or metastatic cancer. Multivariate logistic regression analyses were performed to explore the relationship between serum alkaline phosphatase and active cancer in these patients. Results Among the 249 patients classified as having cryptogenic stroke, 64 had active cancer. Patients with cryptogenic stroke with active cancer had significantly higher serum alkaline phosphatase levels (486±497 vs. 259±88.2 U/L; p<0.001) than those without cancer. Multivariate logistic analysis revealed that serum alkaline phosphatase levels ≥286 U/L were associated with cryptogenic stroke with active cancer [odds ratio (OR), 2.669, 95% confidence interval (CI), 1.291-5.517; p=0.008] independent of age ≤70 years old (OR, 3.303, 95% CI, 1.569-6.994; p=0.002), male sex (OR, 0.806, 95% CI, 0.380-1.710; p=0.573), and serum D-dimer levels ≥2.6 μg/mL (OR, 18.78, 95% CI, 8.130-43.40; p<0.001). Conclusion In patients with cryptogenic stroke, high serum alkaline phosphatase levels may be related to active cancer.

Proof-of-concept study to evaluate the safety and efficacy of saroglitazar in patients with primary biliary cholangitis

Saroglitazar is a novel peroxisome proliferator-activated receptor (PPAR) agonist with dual agonistic properties (α/γ). Due to a strong mechanistic rationale, we aimed to test the safety and efficacy of saroglitazar in patients with primary biliary cholangitis (PBC) who were either ursodeoxycholic acid (UDCA) resistant or intolerant. In this double-blind, phase II proof-of-concept trial, 37 patients with PBC were randomized to saroglitazar 4 mg (n= 13), saroglitazar 2 mg (n= 14), or placebo (n= 10) daily for 16 weeks. The primary efficacy endpoint was the reduction in alkaline phosphatase (ALP) level at Week16. A significant reduction of mean ALP levels was observed at Week 16 relative to baseline in both the saroglitazar 4 mg (least-squares [LS] mean=-163.3 U/L, SE= 25.1, p <0.001) and 2 mg (LS mean=-155.8 U/L, SE= 24.4, p <0.001) groups, compared with placebo (LS mean=-21.1 U/L, SE= 28.9). Treatment with saroglitazar resulted in a rapid reduction of ALP concentration at Week 4 that was sustained through the study duration. At least 1 treatment-emergent adverse event occurred in 11 (84.6%) patients in the saroglitazar 4 mg group, in 12 (85.7%) patients in the 2 mg group and in 8 (80%) patients in the placebo group. Study drug was discontinued in 4 patients (3 patients in the 4 mg group and 1 patient in the 2 mg group) due to aminotransferase increases that promptly returned to baseline values after drug discontinuation. Saroglitazar at 2 mg and 4 mg daily was tolerated and resulted in rapid and sustained improvements in ALP. Further studies are underway at a daily dose of 2 mg and 1 mg due to the higher incidence of elevated liver enzymes observed with the 4 mg dose. CLINICALTRIALS. NCT03112681 LAY SUMMARY: Saroglitazar resulted in a rapid and sustained improvement in alkaline phosphatase levels in patients with primary biliary cholangitis. The mean percentage reductions in alkaline phosphatase levels were 49% and 51% in the saroglitazar 4 mg and 2 mg groups compared to 3% in the placebo group.

Effect of platelet-rich fibrin membrane on gingival crevicular fluid alkaline phosphatase levels in patients undergoing periodontally accelerated osteogenic orthodontics

BackgroundThe present study is aimed to compare the osteoblastic activity in periodontally accelerated osteogenic orthodontics (PAOO) with and without the platelet-rich fibrin (PRF) membrane by evaluating the gingival crevicular fluid (GCF), alkaline phosphate (ALP) levels and also to explore the efficiency of PRF membrane in terms of healing. MethodsA split-mouth randomized controlled trial, which comprised 16 sites, was randomly treated with PAOO + PRF membrane and PAOO alone. The primary outcome was to analyze the GCF ALP levels at baseline, 3rd, week, 5th week (2 weeks after surgery, 1 h before and after activation), 7th week (4 weeks after surgery), and 9th week (6 weeks after surgery). The clinical parameters (plaque index [PI], gingival index [GI], bleeding index [BI]) were assessed at baseline, 3rd week, 15th week, and 27th week. Healing index was recorded at 4th week (1 week after surgery), 5th week (2 weeks after surgery), and 7th week (4 weeks after surgery). ResultsThere was a statistically significant increase in GCF ALP levels (p < 0.05) in the test site (PAOO with PRF membrane) 2 weeks post-surgically compared to the control site. Improvement in the clinical measures (PI, GI, BI) was statistically significant at all time intervals. Adjunctive use of PRF resulted in statistically significant early healing in the first postoperative week compared to the control site (p < 0.05). ConclusionsWithin the limitations of this split-mouth study, PRF membrane showed significant osteoblastic activity in the 5th week (2 weeks after PAOO) with the increased GCF ALP levels and accelerated healing in the 1st week after PAOO. They also maintained post-orthodontic stability until 18 months.

Low serum alkaline phosphatase levels in patients with chronic liver diseases: Possible contributions to disease pathogenesis

ObjectivesA low serum alkaline phosphatase (ALP) level is an uncommon finding in patients with chronic liver disease (CLD). The prevalence of this finding and whether low ALP expression influences CLD remain to be determined. The objectives of this study were: (1) to document the prevalence of low serum ALP levels in adult CLD patients and (2) compare features of CLD in patients with low versus normal or elevated serum ALP levels. MethodsAn adult, outpatient liver disease database was searched for patients with low serum ALP levels (<40 IU/L). Hepatic inflammation, function, fibrosis and disease severity were determined by serum aminotransferases, albumin, bilirubin and INR levels, Fib-4 calculations and MELD scores respectively. ResultsOf 19,037 patients entered into the database, 47 (0.25%) had consistently low serum ALP levels, 51 (0.27%) low levels on the majority and 469 (2.44%) on the minority of determinations. Patients with consistently low levels were matched (1:2) by age, gender and nature of the underlying liver disease to patients with normal or elevated serum ALP levels. Matched patients with consistently low ALP levels had significantly lower serum aminotransferase and bilirubin levels at their initial visit and throughout the follow-up period (p < 0.05 respectively) while Fib-4 levels and MELD scores were similar at the initial and last follow-up visit. ConclusionsThese results establish the prevalence of low serum ALP levels in adult CLD patients and describe a hitherto unreported association between low serum ALP levels and less biochemical evidence of active disease.

Serum Calcium and Serum Alkaline Phosphatase Levels and their Correlations with Disease Activity in Patients with Rheumatoid Arthritis

Rheumatoid Arthritis is a systemic autoimmune disease, characterized by chronic synovial inflammationleading to joint destruction and bone erosion. Metabolic changes have been studied in rheumatoid arthritis,with several studies reported decrease in serum calcium, and increase in serum alkaline phosphatase inrheumatoid arthritis patients in comparison to healthy individuals. This study has been undertaken toevaluate serum calcium and serum alkaline phosphatase levels in patients with rheumatoid arthritis, andtheir correlation with disease activity. A total of 100 patients with rheumatoid arthritis were enrolled in thestudy and compared with 50 healthy controls (46 female: 4 male) matched for age and sex. No significantdifferences have been noticed in mean values of serum calcium, corrected calcium, and serum alkalinephosphatase in patients with rheumatoid arthritis and healthy controls. The mean values of serum calcium,corrected calcium and serum alkaline phosphatase levels were slightly higher with moderate and high diseaseactivity in comparison to low disease activity in patients with rheumatoid arthritis, but the differences didnot reach the statistical significance.

Association between serum ficolin-1 level and disease progression in primary biliary cholangitis.

Pattern recognition molecules (PRMs) in the complement system contribute to homeostasis as mediators of complement activation. The contribution of PRMs to primary biliary cholangitis (PBC) is unknown. In the current study, we aimed to assess the association between PRMs and the clinical findings of PBC. A total of 122 PBC patients and 20 healthy controls were enrolled. We measured four different PRMs (mannose-binding lectin [MBL], ficolin-1, ficolin-2 and ficolin-3) using stored sera, and retrospectively analyzed the associations between PRMs and laboratory findings, histological findings, and the development of cirrhosis-related conditions. Ficolin-1 levels were significantly higher in the PBC patients than in the healthy controls (152 ng/mL vs 102 ng/mL, P = 0.034), but no significant differences were observed regarding MBL, ficolin-2, and ficolin-3 levels. Ficolin-1 was significantly correlated with alkaline phosphatase (ALP). Low ficolin-1 levels were significantly associated with the development of cirrhosis-related conditions independent for histological stage and ALP levels (hazard ratio: 0.933; 95% confidence interval: 0.875–0.994; P = 0.032). Patients with low levels of ficolin-1 (< 77 ng/mL) had a significantly increased rate of developing cirrhosis-related conditions. Low ficolin-1 levels were associated with disease progression independent of histological stage and ALP levels in patients with PBC.

Diagnostic Accuracy of Ultrasound in Correlation to Alkaline Phosphatase Levels in Patients with Biliary Obstructions

Abdominal Ultrasonography (USG) is an appropriate initial screening method for detection of biliary tract disease the consultants sometimes encounter patients who only have findings of dilatation of the Common Bile Duct (CBD) on US without specic biliary symptoms or jaundice.

Alkaline Phosphatase is not Associated with Insulin Resistance: A Retrospective Cross-Sectional Study

Background: Many epidemiologic studies suggested that vitamin D deficiency is associated with obesity but the relationship between obesity and alkaline phosphatase (ALP) is controversial. In this study association between insulin resistance and alkaline phosphatase is investigated. Methods: Of the 124 women aged (35,942±9,714) years with (39,47±7,66) body mass index (BMI) and with vitamin D deficiency is included. The relationship among insulin, glucose, parathormone (PTH), calcium (Ca), alkaline phosphatase (ALP) were evaulated with correlation, linear regression and ANOVA (with post hoc TUKEY). Statistical analysis performed with Eviews v.11 and Graphpad Prism v.8.1 Results: There was no significant correlation among Vitamin D, ALP and PTH in non-insulin resistance patients. A weak correlation was found among Vitamin D, ALP and Parathormone in insulin resistance group. There was no significant elevation between ALP levels in patients with or without insulin resistance. Conclusion: Elevation in ALP levels is not associated with insulin resistance. It might be a response to elevated parathormone levels. Further investigations in large populations are required to understand the relationship between insulin resistance and ALP.

The Impact of Serum Magnesium Level Disorders on Parathyroid Hormone and Alkaline Phosphatase Levels in Patients with Chronic Kidney Disease Stage 5 under Maintenance Hemodialysis

The Impact of Serum Magnesium Level Disorders on Parathyroid Hormone and Alkaline Phosphatase Levels in Patients with Chronic Kidney Disease Stage 5 under Maintenance Hemodialysis

Association between increased serum alkaline phosphatase and the coronary slow flow phenomenon

BackgroundDespite marked advances in our understanding of the pathophysiology of the coronary slow flow phenomenon (CSFP), the exact mechanism remains unclear. Previous studies have suggested that CSFP might be associated with generalized atherosclerosis, endothelial dysfunction, and low-grade chronic inflammation. High serum alkaline phosphatase (ALP) levels are associated with vascular calcification, atherosclerotic disease, and an increased risk of cardiovascular events. However, the relationship between ALP and CSFP is unclear.MethodsWe investigated 64 patients with angiographically proven CSFP and 50 with normal coronary flow. Serum ALP levels were measured in all studied individuals.ResultsSerum ALP levels in patients with CSFP were significantly higher than those in the control group (70.5 ± 17.1 vs. 61.9 ± 16.1 U/L, P = 0.007). A positive association was observed (r = 0.42, P = 0.032) between serum ALP levels and the mean thrombolysis in myocardial infarction frame count (mTFC). Regression analysis showed a high serum ALP level was the only independent predictor of the mTFC (β = 0.309, P < 0.001). Moreover, our study showed that a serum ALP level > 67.5 U/L was a predictor of CSFP (sensitivity = 83.3%, specificity = 84.1%).ConclusionsPatients with CSFP show high serum ALP levels, which may be associated with the pathogenesis of CSFP. A high serum ALP level is a predictor of CSFP. Future studies are needed to clarify the role of ALP in patients with CSFP.

Seladelpar (MBX-8025), a selective PPAR-δ agonist, in patients with primary biliary cholangitis with an inadequate response to ursodeoxycholic acid: a double-blind, randomised, placebo-controlled, phase 2, proof-of-concept study

Many patients with primary biliary cholangitis have an inadequate response to first-line therapy with ursodeoxycholic acid. Seladelpar is a potent, selective agonist for the peroxisome proliferator-activated receptor-delta (PPAR-δ), which is implicated in bile acid homoeostasis. This first-in-class study evaluated the anti-cholestatic effects and safety of seladelpar in patients with an inadequate response to ursodeoxycholic acid. The study was a 12-week, double-blind, placebo-controlled, phase 2 trial of patients with alkaline phosphatase of at least 1·67 times the upper limit of normal (ULN) despite treatment with ursodeoxycholic acid. Patients, recruited at 29 sites in North America and Europe, were randomly assigned to placebo, seladelpar 50 mg/day, or seladelpar 200 mg/day while ursodeoxycholic acid was continued. Randomisation was done centrally (1:1:1) by a computerised system using an interactive voice-web response system with a block size of three. Randomisation was stratified by region (North America and Europe). The primary outcome was the percentage change from baseline in alkaline phosphatase over 12 weeks, analysed in the modified intention-to-treat (ITT) population (any randomised patient who received at least one dose of medication and had at least one post-baseline alkaline phosphatase evaluation). This study is registered with ClinicalTrials.gov (NCT02609048) and the EU Clinical Trials Registry (EudraCT2015-002698-39). Between Nov 4, 2015, and May 26, 2016, 70 patients were screened at 29 sites in North America and Europe. During recruitment, three patients treated with seladelpar developed fully reversible, asymptomatic grade 3 alanine aminotransferase increases (one on 50 mg, two on 200 mg), ranging from just over five to 20 times the ULN; as a result, the study was terminated after 41 patients were randomly assigned. The modified ITT population consisted of 12 patients in the placebo group, 13 in the seladelpar 50 mg group, and 10 in the seladelpar 200 mg group. Mean changes from baseline in alkaline phosphatase were -2% (SD 16) in the placebo group, -53% (14) in the seladelpar 50 mg group, and -63% (8) in the seladelpar 200 mg group. Changes in both seladelpar groups versus placebo were significant (p<0·0001 for both groups vs placebo), with no significant difference between the two seladelpar groups (p=0·1729). All five patients who received seladelpar for 12 weeks had normal alkaline phosphatase values at the end of treatment, based on a central laboratory ULN for alkaline phosphatase of 116 U/L. The most frequently reported adverse events were pruritus (16%; one patient on placebo, four on seladelpar 50 mg, and one on seladelpar 200 mg), nausea (13%; one patient on placebo, three on seladelpar 50 mg, and one on seladelpar 200 mg), diarrhoea (10%; two patients on placebo, one on seladelpar 50 mg, and one on seladelpar 200 mg), dyspepsia (8%; two patients on seladelpar 50 mg and one on seladelpar 200 mg), muscle spasms (8%; three patients on seladelpar 200 mg), myalgia (8%; one patient on placebo and two on seladelpar 200 mg), and dizziness (8%; one patient on placebo and two on seladelpar 50 mg). Seladelpar normalised alkaline phosphatase levels in patients who completed 12 weeks of treatment. However, treatment was associated with grade 3 increases in aminotransferases and the study was stopped early. The effects of seladelpar should be explored at lower doses. CymaBay Therapeutics.