Higher iPTH Research Articles

Association of Secondary Hyperparathyroidism and Hyperkalemia in Hemodialysis-dependent Chronic Kidney Disease Patients

Abstract Introduction: Hyperparathyroidism secondary to chronic renal failure is a condition characterized by increased secretion of parathyroid hormone (PTH), secondary to hyperphosphatemia and hypocalcemia. In dialysis patients’ hyperkalemia is a frequent electrolyte disturbance that may result in various complications. Objectives: The study aimed to determine the association of secondary hyperparathyroidism (SHPTH) with hyperkalemia in hemodialysis patients. There is very little literature on the direct relationship of hyperparathyroidism with hyperkalemia. Materials and Methods: This is an observational study of hemodialysis patients visiting a university hospital for maintenance hemodialysis. Patients were randomly selected for the study who were visiting the Department of Nephrology for their regular maintenance hemodialysis program. Serum PTH analysis was done by chemiluminescence method. Serum potassium >5.5 mEq/L was considered hyperkalemia, and serum intact PTH (iPTH) >300 pg/mL was considered as SHPTH. Results: The study included 59 participants from dialysis-dependent chronic kidney disease patients. In this study, 64.4% of the participants were male and 35.6% were female. The mean age of the study group was 47.64 ± 13.042 years. 44.1% of the participants had hyperkalemia, and 43.1% of the participants had SHPTH. 89.7% of the patients with SHPTH had hyperkalemia. The mean serum potassium in the iPTH ≤300 pg/mL group was 4.50 mEq/L. The mean serum potassium in the iPTH >300 pg/mL group was 6.33 mEq/L. 90.9% of the participants in the group iPTH: ≤300 pg/mL had serum potassium: ≤5.5 mEq/L while 88.0% of the participants in the group iPTH: >300 pg/mL had serum potassium: >5.5 mEq/L. There was a strong positive correlation between iPTH and serum potassium, and this correlation was statistically significant (rho = 0.72, P ≤ 0.001). Conclusion: The present study shows a statistically significant association of iPTH (SHPTH) and serum potassium (hyperkalemia), and high iPTH is positively associated with hyperkalemia.

Association between serum intact parathyroid hormone and survival in dialysis patients.

To examine the relationship between serum intact parathyroid hormone (iPTH) levels and survival in maintenance dialysis patients. We retrospectively reviewed the data of patients who began and continued dialysis from January 2013 to December 2022. Patients were categorized based on their baseline and time-averaged (TA) iPTH levels into three groups: low (iPTH < 150pg/ml), medium (150 ≤ iPTH < 300pg/ml), and high (iPTH ≥ 300pg/ml). We utilized the Kaplan-Meier method to assess survival differences, the Cox proportional hazards regression model to identify risk factors impacting adverse outcomes and the restricted cubic spline model to evaluate the association between iPTH levels and the all-cause mortality. We included a total of 1023 participants, comprising 524 hemodialysis and 499 peritoneal dialysis. Kaplan-Meier analysis showed that high baseline group had higher survival and low baseline group had poorer survival, compared with medium baseline group, respectively (χ2 = 44.974, P < 0.001). The three TA groups showed similar results (χ2 = 67.316, P < 0.001). Multivariate COX regression analysis showed that low TA iPTH was an independent risk factor for all-cause death (hazard ratio [HR] = 1.655, 95% CI 1.159-2.365, P = 0.006). The restricted cubic spline model revealed an L-shaped connection between TA iPTH level and the all-cause mortality with an inflection point of 193pg/ml. The survival for maintenance dialysis patients varies significantly based on their baseline and time-averaged iPTH levels, with time-averaged iPTH emerges as an independent risk factor for all-cause death in these patients.

Serum 25(OH)D Levels and Mitral Valve Calcification in Patients with Severe Rheumatic Mitral Stenosis

Background: Rheumatic heart disease (RHD) imposes a significant burden on patients and the health system, especially in the developing countries. Recently, the role of vitamin D deficiency in increasing the severity of valve involvement and calcification in patients with RHD has been suggested. However, its role in the severe stenosis of the mitral valve is unknown. The aim of this study was to determine the relationship between serum levels of 25(OH)D and mitral involvement severity scores in patients with severe mitral stenosis (MS). Materials and Methods: In this cross-sectional study conducted in Shahid Madani Heart Center, Tabriz, Iran, 104 patients with severe rheumatic MS were reviewed, in the absence of other underlying diseases. Trans-esophageal Echocardiography was performed for all patients, and mitral valve Wilkins score and mitral valve area were calculated. Blood samples were taken from patients and levels of 25(OH)D, total calcium, phosphorus, and i-PTH were measured. Results: Eighty eight cases were female and 16 were male. Eighty-one patients had mild to moderate mitral calcification and in 23 patients with mitral valve was severely calcified. Furthermore, 54 were vitamin D deficient, while 35 had insufficient vitamin D levels, and only 15 had normal blood levels of vitamin D. In addition high serum iPTH levels were present in 83 patients (80%). The levels of 25(OH)D, calcium, phosphorous, and iPTH with total Wilkins score, calcification score and mitral valve area were not significantly correlated (p&gt;0.05 for all above). Conclusions: Although no correlation was found between the severity of mitral valve involvement, and vitamin D and iPTH levels, vitamin D deficiency and secondary hyperparathyroidism tend to be common among patients with severe rheumatic MS, which may play a role in the progression of the disease.

Efficacy of iguratimod on mineral and bone disorders after kidney transplantation: a preliminary study

Background Iguratimod has been shown to promote bone formation and inhibit bone resorption in rheumatoid arthritis patients. We aimed to explore its effect on bone metabolism and vascular calcification (VC) in kidney transplant recipients (KTRs). Methods A post hoc analysis was conducted among the subjects in our previous randomized clinical trial (NCT02839941). Forty-three KTRs completing bone metabolism 52 weeks after enrollment were selected for this analysis, among whom 27 patients received VC examinations. In the iguratimod group, iguratimod (25 mg twice daily) was added adjuvant to the traditional triple regimen. At the 52-week follow-up, the following parameters were assessed: serum calcium, phosphorus, 25-hydroxyvitamin D, intact parathyroid hormone (iPTH), bone alkaline phosphatase (BALP), osteocalcin, type I collagen N-terminal peptide (NTx), type I collagen C-terminal peptide (CTx), bone mineral density (BMD) of the femoral neck and lumbar spine, coronary artery calcification (CAC) and thoracic aortic calcification (TAC). Bone metabolic and VC indices were compared between the two groups using the independent samples t test and Wilcoxon nonparametric test. Results At 52 weeks after enrollment, the iguratimod group had lower osteocalcin (p = 0.010), BALP (p = 0.015), NTx (p = 0.007), CTx (p = 0.012), CAC (p = 0.080) and TAC scores (p = 0.036) than the control group. There was no significant difference in serum calcium, phosphorus, 25-hydroxyvitamin D, iPTH and BMD between the groups. Iguratimod could reduce bone turnover markers (BTMs) at both high and low iPTH levels. The adverse effect of iguratimod was mild and tolerable. Conclusion Iguratimod is safe, can reduce BTMs and may could attenuate VC in the first year after KT.

Changes in Bone Mineral Density and Related Influencing Factors Assessed by Quantitative Computed Tomography in Maintenance Dialysis Patients.

To investigate the changes in volumetric bone mineral density (vBMD) assessed by quantitative computed tomography (QCT) in chronic kidney disease (CKD) patients on maintenance dialysis. Descriptive study. Place and Duration of the Study: Department of Radiology, The Second Affiliated Hospital of Anhui Medical University, Hefei, China, from March to July 2022. Maintenance dialysis patients were selected for this study, and parameters related to renal function and bone metabolism markers were recorded. Patients undergoing routine physical examination were age-matched with maintenance dialysis patients to serve as the control group. vBMD scans of the lumbar spine (L1-3) were obtained by QCT for all participants. Among the 141 maintenance dialysis patients, there were 67 patients with secondary hyperparathyroidism (SHPT) and 74 patients with non-secondary hyperparathyroidism (non-SHPT) with mean vBMDs of 145.99±55.13 mg/cm3 and 129.10±44.20 mg/cm3, respectively. The 159 individuals in the control group had mean age of 52.77±11.66 years and mean vBMD of 129.62±36.36 mg/cm3. The vBMD of the SHPT group was greater than that of both the non-SHPT group and the control group (all p<0.05). For dialysis patients, vBMD was positively correlated with calcium-phosphorus product and intact parathyroid hormone (iPTH) levels (r = 0.181, 0.214, respectively, p<0.05); vBMD was inversely correlated with age (r = -0.555, p<0.05). After adjusting for the covariates, vBMD remained positively correlated with iPTH (r = 0.184, p<0.05). Increased lumbar vertebral vBMD in maintenance dialysis patients may be associated with high iPTH, providing clinicians with a new understanding of the changes in bone mineral density in maintenance dialysis patients. Bone mineral density, Quantitative computed tomography, Chronic kidney disease, Maintenance dialysis.

Associations of calcium, phosphate and intact parathyroid hormone levels with mortality, residual kidney function and technical failure among patients on peritoneal dialysis.

Associations of calcium, phosphate and intact parathyroid hormone (iPTH) levels with outcomes may be different between patients on peritoneal dialysis (PD) and hemodialysis (HD). The aim of the study is to evaluate these associations among PD patients. In this prospective cohort study on the Japan Renal Data Registry, adults on PD at the end of 2009 were included. The observation period was until the end of 2018 and the data were censored at the time of transplantation or transition to HD. Exposures were time-averaged or time-dependent albumin-corrected calcium (cCa), phosphate and iPTH levels. Outcomes were all-cause and cardiovascular mortality, transition to HD and urine output. Data were analyzed using Cox regression models or linear mixed-effects models and the results were shown as cubic spline curves. Among 7393 patients, 590 deaths and 211 cardiovascular deaths were observed during a median follow-up of 3.0 years. Higher cCa and phosphate levels were associated with higher mortality. Lower cCa levels were associated with a faster decline, whereas lower phosphate was associated with a slower decline in urine output. Lower phosphate and iPTH levels were associated with a lower incidence of transition to HD. Among PD patients, the observed associations of cCa, phosphate and iPTH with mortality, residual kidney function and technical failure suggest that avoiding high cCa, phosphate and iPTH levels might improve outcomes.

Post Hoc Analysis of National Institute of Child Health and Human Development Vitamin-D Pregnancy Cohort and The Role of Functional Vitamin-D Deficiency in Pregnancy.

Our objective was to conduct a secondary, post hoc analysis of the National Institute of Child Health and Human Development (NICHD) vitamin D (vitD) pregnancy study by Hollis et al, which reported on the effect of vitD supplementation in pregnant women and determine the potential interaction between intact parathyroid hormone (iPTH) concentrations, vitD status, and various comorbidities associated with pregnancy. Women with low 25-hydroxy vitamin D (25(OH)D) concentrations and high iPTH concentrations during pregnancy, known as functional vitamin-D deficiency (FVDD), were more likely to acquire complications also affecting their neonates. This post hoc analysis of data collected from a diverse group of pregnant women participating in the NICHD vitD pregnancy study was applied to investigate the applicability of the concept of FVDD in pregnancy (Hemmingway, 2018) in identifying potential risks for certain comorbidities of pregnancy. This analysis defines FVDD as maternal serum 25(OH)D concentrations below 20 ng/mL and iPTH concentrations above 65 pg/mL creating a definitive ratio number, 0.308, to classify mothers as having FVDD prior to delivery (PTD). Statistical analyses were performed using SAS 9.4 (Cary, NC). In total, 281 women (85 African American, 115 Hispanic, and 81 Caucasian) with 25(OH)D and iPTH concentrations measured at monthly visits were included in this analysis. No statistically significant association was found between mothers classified as having FVDD at baseline or 1-month PTD and hypertensive disorders of pregnancy, infection, or admittance to the neonatal intensive care unit. When combining all comorbidities of pregnancy in this cohort, results showed those with FVDD at baseline, 24 weeks' gestation, and 1-month PTD were more likely to experience a comorbidity (p = 0.001; p = 0.001; p = 0.004, respectively). Those with FVDD 1-month PTD were 7.1 times (confidence interval [CI]: 1.71-29.81) more likely to have preterm birth (<37 weeks) than women without FVDD. Participants were more likely to have experienced preterm birth if they met the criteria for FVDD. This study supports the importance of FVDD during pregnancy. · Functional vitamin D deficiency (FVDD) is defined as the ratio of 25(OH)D divided by iPTH concentration ≤0.308.. · At a minimum, it is recommended that vitamin D status be kept in the healthy range based on current recommendations for pregnant individuals.. · FVDD is a more sensitive predictor of pregnancy risk than 25(OH)D alone.. · FVDD identified those with greater risk of preterm birth in this cohort..

Associated factors of osteoporosis and vascular calcification in patients awaiting kidney transplantation

IntroductionPretransplant osteoporosis and vascular calcification probably increase the risk of fractures and cardiovascular events after kidney transplantation. In the present study, we investigated the related risk factors of osteoporosis and vascular calcification among end-stage renal disease (ESRD) patients awaiting kidney transplantation.MethodsA total of 221 ESRD patients (age, 43.4 ± 14.3 years; 125 males and 96 females; median dialysis duration, 61.0 m) awaiting kidney transplantation were enrolled in this cross-sectional study. Serum levels of bone turnover markers and intact parathyroid hormone (iPTH) were analyzed from fasting morning blood samples. Dual-energy X-ray absorptiometry was used to measure bone mineral density (BMD). Vascular calcification was evaluated by lateral abdominal radiography and plain radiographic films of the pelvis and hands.ResultsThe osteoporosis prevalence was 27.6% in this cohort of kidney transplantation candidates, and the prevalence of vascular calcification was 51.1%. The related factors for osteoporosis and vascular calcification were similar and included older age, longer dialysis duration, parathyroid hyperplasia, and higher levels of iPTH and bone turnover markers. In the multivariable regression model, age and iPTH were independent risk predictors of both vascular calcification and osteoporosis. There were strong, positive correlations between iPTH and all bone turnover markers. The moderate and severe hyperparathyroidism (iPTH 600–1499 pg/ml and iPTH 1500 pg/ml) were related to reduced serum albumin and hemoglobin levels.ConclusionThe involvement of high iPTH levels in vascular calcification, osteoporosis, and malnutrition indicated the need of treating hyperparathyroidism early in patients awaiting kidney transplantation. Prospective studies are needed to further examine the utility of bone turnover markers.

Agreement of Parathyroid Hormone Status Measured by Intact and Biointact Parathyroid Hormone Assays among Chronic Kidney Disease Patients and Its Correlation with Bone Turnover Parameters.

This study aimed to determine the agreement between intact parathyroid hormone (iPTH) and biointact parathyroid hormone (bio-PTH) assays and to correlate them with bone markers. This cross-sectional study included 180 patients with chronic kidney disease (CKD) stages 3b, 4 and 5D. We measured their iPTH, bio-PTH, 25-hydroxyvitaminD (25(OH)D), C-terminal telopeptide collagen (CTX), procollagen 1 intact N-terminal propeptide (P1NP), calcium, phosphate and alkaline phosphatase (ALP). Higher iPTH than bio-PTH concentrations were seen in CKD stages 3b, 4 and 5D (58[62] versus 55[67] pg/mL, 94[85] versus 85[76] pg/mL and 378[481] versus 252[280] pg/mL, respectively). Both PTH assays showed good agreement among all the subjects, with an intraclass correlation coefficient of 0.832 (P-value < 0.001). The Passing-Bablok showed that the equation for the bio-PTH was PTH = 0.64 iPTH + 15.80, with r = 0.99. The Bland-Altman plots showed increased bias with an increasing PTH concentration. Both PTH assays showed a high positive correlation with CTX and P1NP, a moderate correlation with phosphate, a low correlation with ALP and calcium, and a negligible correlation with phosphate and 25(OH)D. The iPTH and bio-PTH assays were in agreement, but their bias increased with the PTH concentration. The unacceptable large bias indicates that the two assays cannot be used interchangeably. They had a variable correlation with the bone parameters.

Risk factors for intracerebral hemorrhage in patients undergoing maintenance hemodialysis.

In patients undergoing hemodialysis, intracerebral hemorrhage (ICH) is the main cause of mortality among stroke subtypes. It is unclear whether, along with traditional cardiovascular risk factors, the risk factors unique to the uraemic environment, such as the abnormal metabolism of intact parathyroid hormone (iPTH), can contribute to the risk of ICH in these patients. This retrospective case-control study included 25 patients undergoing hemodialysis with ICH at a single center between 30 June 2015 and 10 October 2022. The controls were 95 patients undergoing maintenance hemodialysis treated at the same dialysis center in July 2020. We compared the characteristics of patients with ICH with those of the control group to identify factors that contributed to the development of ICH. Intracerebral hemorrhage (ICH) was located in the basal ganglia (14/25), cerebellum (6/25), and brainstem (6/25) in 25 patients. A total of 17 patients died in the first 16 days due to neurological complications. Univariate analysis showed significant differences in systolic BP, diastolic BP, iPTH, and alkaline phosphatase between the two groups (p < 0.05). Multivariate logistic regression analysis showed that higher systolic BP (OR, 1.053; 95% CI, 1.018-1.090; p = 0.003) and higher iPTH (OR, 1.007; 95% CI, 1.003-1.012; p = 0.001) were associated with the onset of ICH. ICH was predicted by systolic BP and iPTH by receiver operating characteristic (ROC) curve analysis, with areas under the curve (AUCs) of 0.732 and 0.624, respectively. The optimal cutoffs for systolic BP and iPTH were 151.9 mmHg and 295.4 pg./ml, respectively. Restricted cubic spline showed that the shape of the association of iPTH with the risk of ICH was approximately J-shaped (P for non-linearity <0.05). Higher systolic BP and abnormal iPTH metabolism might be associated with ICH in patients undergoing hemodialysis. Comprehensive control of hypertension and iPTH may be a fundamental preventive strategy for ICH in these patients.

Evaluation of T helper17 as skeletal homeostasis factor in peripheral blood mononuclear cells and T helper cells of end-stage renal disease cases with impaired parathyroid hormone.

Chronic renal failure is mainly connected with high and low parathyroid hormone (PTH) levels and immunological impairments. The present study aimed to evaluate T helper 17 (Th17) cells as a crucial modulator of the immune system and skeletal homeostasis in hemodialysis patients with impaired intact PTH (iPTH). In this research, blood samples were taken from ESRD patients with high (> 300 pg/mL), normal (150-300 pg/mL), and low (< 150 pg/mL) serum intact parathyroid hormone (iPTH( levels (n = 30 in each group). The frequency of Th17 (CD4+ IL17+) cells was evaluated by flow cytometry in each group. The expression levels of Th17 cell-related master transcription factors, cytokines in peripheral blood mononuclear cells (PBMC), and Th cells, and the level of the mentioned cytokines were determined in the supernatant of PBMCs. The number of Th17 cells remarkably increased in subjects with high iPTH against low and normal iPTH. Also, RORɣt and STAT3 levels were significantly higher in high iPTH ESRD patients than in other groups in the expression of mRNA and protein levels. These findings are confirmed by evaluating the IL-17 and IL-23 in the supernatant of cultured PBMCs and isolated Th cells. Our findings indicated that increased serum PTH levels in hemodialysis cases may be involved in increasing the differentiation of CD4 + cells to Th17 cells in PBMC.

Effect of Roxadustat versus erythropoietin (EPO) for treating anemia in patients with diabetic kidney disease: a retrospective cohort study

Renal anemia of diabetic kidney disease (DKD) shows higher incidence rate, earlier onset and higher severity than other chronic kidney disease (CKD). Roxadustat, an oral hypoxia-inducible factor-prolyl hydroxylase inhibitor, improves CKD anemia. This retrospective cohort study evaluates if Roxadustat could effectively treat DKD anemia. DKD anemia patients treated with either Roxadustat or erythropoietin (EPO) for 3 months in two hospitals were enrolled. EPO group were matched 1:1 to Roxadustat group based on age, gender and baseline Hb. Baseline data include age, sex, dialysis, height, weight, hemoglobin (Hb), hematocrit (Hct), serum albumin (ALB), serum creatinine (Scr), eGFR, C-reactive protein (CRP), and intact parathyroid hormone (iPTH). Primary and secondary outcomes were change of Hb (ΔHb) and Hct (ΔHct), Hb response rate and Hb qualified rate. Sensitivity analyses were performed and the effect size were calculated. No significant differences were observed in body mass index (BMI), Scr, eGFR, Hct, CRP, and dialysis between the 2 groups (61 subjects each). ALB, iPTH, and DKD stage differed between the 2 groups. After 3-month treatment, Roxadustat significantly increased patients' Hb and Hct. Although ΔHb and ΔHct of the Roxadustat group was higher than those of EPO group, difference in the least-square mean changes (95% CI) were 4.9 (-2.4, 12.1) and 1.2 (-1.1, 3.4), while Cohen's d were 0.18 and 0.14, suggesting that Roxadustat's ability to increase Hb within 3-month was similar to EPO. 78.7% and 54.1% of the patients responded to anti-anemia therapy in the Roxadustat and EPO group, respectively. Logistic regression analysis showed the Hb response rate of Roxadustat was 3.30 (1.20, 9.94) times higher than that of EPO. Subgroup analysis suggested that Roxadustat might have better efficacy in treating patients in the advanced stage, with high CRP and iPTH, and low ALB levels. In DKD patients, Roxadustat improves renal anemia. Effect of Roxadustat is similar to that of EPO.

High C-Terminal Fibroblast Growth Factor-23, Intact Parathyroid Hormone, and Interleukin-6 as Determinants of Valvular Calcification in Regular Hemodialysis Patients.

PurposeBiggest cause of death in chronic kidney disease-hemodialysis (CKD-HD) patients is cardiovascular disease (CVD). Cardiovascular disease is often associated with mineral bone disorders (MBD), especially vascular and valvular calcification. Biomarkers such as C-terminal-fibroblast growth factor-23 (FGF-23), intact parathyroid hormone (iPTH), and interleukin-6 (IL-6) were investigated. Only few studies have focused on valvular calcification in CKD-HD patients, with controversial results. The present study aimed to investigate whether high C-terminal-FGF-23, iPTH, and IL-6 can be used as determinants of valvular calcification in CKD-MBD patients undergoing regular HD.Patients and MethodsThis was an analytical cross-sectional study which involved CKD-HD patients aged 18–60 years with no history of CVD, malignancy, and diabetes mellitus. C-terminal FGF-23 was measured using enzyme-linked immunosorbent assay (ELISA) kit, iPTH using chemiluminescent immunometric method, and IL-6 using sandwich enzyme immunoassay technique. Valvular calcification on aortic and mitral valves was examined with echocardiography. Data analysis was done using Chi-squared test or Fisher’s exact test as appropriate and multivariate logistic regression analysis.ResultsBivariate analysis with Fisher’s exact test showed significant association of prevalence ratio (PR) of C-terminal FGF-23 (PR = 1.33; p = 0.003; CI (1.017–1.748)), iPTH (PR = 1.361; p = 0.002; CI (1.02–1.816)), and IL-6 (PR = 1.2; p = 0.019; CI (1.000–1.446)) with valvular calcification. Multivariate analysis with logistic regression showed high C-terminal FGF-23 (exp (B) value of 16.44; p = 0.045; CI (1.07–252.75)), iPTH (exp (B) value of 33.312; p = 0.016; CI (1.94–571.71)), and IL-6 (exp (B) value of 21.58; p = 0.0381; CI (1.18–394.87)) were determinants of valvular calcification in CKD-MBD patients undergoing regular HD.ConclusionThis study demonstrated that high C-terminal FGF-23, iPTH, and IL-6 were determinants of valvular calcification in CKD-MBD patients undergoing regular HD.

POS-754 PERSISTENT HYPERPARATHYROIDISM AFTER KIDNEY TRANSPLANTATION, ITS PREVALENCE AND RISK FACTORS

Persistent hyperparathyroidism (pHPT) is common after successful kidney transplantation (KTx) and is related to pretransplant risk factors. pHPT is associated with increased graft loss, mortality and increased risk of fractures. This study aims to evaluate the prevalence and risk factors for pHPT after KTx. A retrospective study of kidney transplant recipients attending the transplant clinic between November 2018 and March 2020 was performed. The laboratory data of patients (Serum calcium, phosphorus, creatinine, intact parathyroid hormone (iPTH) and estimated glomerular filtration rate (eGFR)) were collected at 12 months posttransplantation and at pretransplantation. The persistency of HPT after transplant was defined as iPTH ≥ 130 pg/mL, and the term "tertiary hyperparathyroidism" (THPT) was used for patients with pHPT how needed parathyroidectomy (PTx). Risk factors for the development of pHPT were investigated by comparing THPT and non-pHPT groups. Data for 80 patients were analyzed. After one year of KTx, HPT persists in 18 patients (22.5%), of whom six patients underwent parathyroidectomy, and 12 patients were kept on conservative management. Compared with non-HPT group, patients with THPT had significantly longer dialysis duration (43 ± 32.6 mo vs 12.6 ± 13.9 mo. P = 0.013), higher pre-KTx iPTH (1138.7 ± 669.8 vs 365.5 ± 178.6 pg/ml, P = 0.001), and higher pre-KTx calcium (10.1 ± 0.61 vs 8.6 ± 0.60 mg/dl, P < 0.0001). Based on our study results, the most important risk factors for post-KT pHPT are long dialysis duration and high pre-KTx iPTH and Ca levels. Therefore, parathyroidectomy must be considered before kidney transplantation in high-risk patients.

Elevated parathyroid hormone levels in older women treated for osteoporosis using denosumab.

Primary care physicians (PCPs) often struggle with elevated serum intact parathyroid hormone (iPTH) in osteoporotic patients on antiresorptive treatment, specifically, denosumab. As iPTH and calcium levels need to be within normal ranges to receive the next dose of denosumab, continuously high serum iPTH may necessitate additional tests to rule out pathological causes. We aimed to determine factors associated with iPTH elevation in a cohort of postmenopausal women receiving osteoporosis treatment. A cross-sectional analysis of electronic medical records of patients 50years and older who visited a geriatric osteoporosis clinic between October 1, 2014 and December 31, 2019, was conducted. We divided patients into 3 categories: not currently on treatment, on bisphosphonates or on denosumab. Percentage change in iPTH levels from baseline to 1year follow-up was the outcome measure. Other variables used are age, body mass index, chronic co-morbidities, 25OH-vitamin D, calcium, TSH, glomerular filtration rate and femoral neck BMD. Linear regression models were used to assess independent associations between treatment group and iPTH changes. Mean (SD) age of 173 participants in our study was 78 (± 10) years, and 71% were Caucasian. At follow-up, mean percent change of iPTH was 13.47 ± 62.76, 30.35 ± 61.17, and 39.60 ± 35.51 in the "no treatment", "bisphosphonate" and "denosumab" groups, respectively. Age was a predictor of elevated percent change of iPTH in the denosumab group. Increasing age is associated with iPTH elevations in osteoporotic patients on denosumab. In the absence of any pathology, continuation of denosumab may be safe in lowering fracture risk. However, a larger study may be required to confirm this.

Association Between Secondary Hyperparathyroidism and Body Composition in Pediatric Patients With Moderate and Advanced Chronic Kidney Disease.

Objective: This single center cross-sectional study aims to investigate the association between secondary hyperparathyroidism and body composition in pediatric patients with moderate (stage 3) and advanced (stage 4–5) chronic kidney disease (CKD).Methods: 61 patients (median age: 13.4 years) were included. Body composition indices, including lean tissue index (LTI) and fat tissue index (FTI), were measured using multi-frequency bio-impedance spectroscopy. Muscle wasting was defined as LTI adjusted to height-age (HA) z-score < −1.65 SD and high adiposity as FTI z-score > 1.65 SD. Serum mineral metabolism parameters, including serum intact parathormone (iPTH), calcium, phosphorus and 25-hydroxyvitamin D, as well as serum leptin were measured in each patient. In advanced CKD patients, the mean values of serum mineral laboratory parameters of the 6 months prior to body composition assessment were recorded, and alfacalcidol index, defined as weekly alfacalcidol dose (mcg/week) per pg/ml of iPTH × 1,000, was calculated.Results: In moderate CKD (31 patients), high iPTH (>90 ng/ml) was observed in 10 (32.3%) patients and was associated with higher FTI z-score (p = 0.022). Moreover, serum iPTH was negatively correlated to LTI HA z-score (rs = −0.486, p = 0.006), and positively correlated to serum leptin levels (rs = 0.369, p = 0.041). The positive correlation between FTI z-score and iPTH (rs = 0.393, p = 0.039) lost significance after adjustment for serum leptin. iPTH was positively associated with high adiposity (12 patients, 38.7%) after adjustment for the other mineral metabolism parameters (OR 1.023, 95% CI 1.002–1.045, p = 0.028). In advanced CKD (30 patients), no significant correlation was observed between iPTH and body composition indices and serum leptin levels. Eleven (36.7%) patients with muscle wasting presented lower alfacalcidol index (p = 0.017). Alfacalcidol index ≤ 24 was strongly associated with muscle wasting after adjustment for CKD stage and other mineral metabolism parameters (OR 7.226, 95% CI 1.150–45.384, p = 0.035).Conclusion: Secondary hyperparathyroidism is associated with high adiposity in moderate but not in advanced CKD, with leptin acting as a potential contributive factor. In advanced CKD, targeting higher alfacalcidol weekly dose per each unit of serum PTH seems beneficial for preventing muscle wasting.

Mild progressive osseous heteroplasia overlap syndrome with PTH and TSH resistance appearing during adolescence and not early childhood

Progressive osseous heteroplasia (POH), a genetic disorder, is associated with Albright's hereditary osteodystrophy (AHO), pseudohypoparathyroidism, and primary osteoma cutis and has common features of superficial ossification and GNAS-inactivating mutations. Disorders due to GNAS-inactivating mutations are classified as "inactivating parathyroid hormone (PTH)/PTHrP signaling disorder type 2." This study reports a case of mild POH overlap syndrome to improve understanding of genotype-phenotype correlations. A 13-year and 6-month-old Japanese boy was referred to our hospital with a chief complaint of the lower limb length difference. He underwent clinical, biochemical, radiological, and genetic studies. He showed sporadic GNAS mutation, deep ectopic ossification, small for gestational age (SGA), congenital tooth defect, and lack of AHO features; he met the diagnostic criteria for POH, and mild PTH and TSH resistance was detected. He had constant hyperphosphatasemia and hypocalciuria. At the age of 10 years, he occasionally experienced high iPTH levels. The pituitary stimulation test showed a normal response of all hormones at 3 years of age, but TSH response was decreased (previously 0.770, peak value 4.144 μIU/mL) in the TRH loading test at age 13 years and 6 months. DNA analysis showed a heterozygous p.D189MfsTer14 mutation of GNAS. The parents did not carry this mutation. We report a rare case of POH overlap syndrome with PTH/TSH resistance that appeared in adolescence rather than early childhood. Cases diagnosed with POH in early childhood also require reassessment during adolescence. Further studies of the GNAS heterozygous mutation p.D189MfsTer14 may reveal factors involved in POH overlap syndrome.

Oral versus intramuscular cholecalciferol replacement in hemodialysis patients with vitamin D deficiency

Introduction: Low 25-hydroxyvitamin D (25(OH)D) level in hemodialysis (HD) patients is associated with high bone turnover, secondary hyperparathyroidism, and decreased bone mineral density (BMD). Objective: To investigate the efficacy of equivalent doses of pulse oral cholecalciferol versus intramuscular (IM) cholecalciferol in correcting serum 25(OH)D levels in HD patients with vitamin D deficiency. Patients and Methods: In a prospective randomized open-label clinical trial, 80 HD patients with 25(OH)D level &lt;20 ng/mL and serum intact parathyroid hormone (iPTH) level &gt;100 pg/mL were enrolled in the study. Patients were divided into two groups. Group I: 40 HD patients received oral cholecalciferol 25 000 IU weekly for 12 weeks. Group II: 40 HD patients received a single dose of IM cholecalciferol 300 000 IU. Patients were maintained on their regular medications as alfacalcidol or phosphate binders. Serum calcium, phosphorus, 25(OH)D, alkaline phosphatase and iPTH were monitored at 0, 6th, and 12th week of intervention. Results: Significant increase in serum 25(OH)D level in group II patients who received IM (intramuscular) cholecalciferol, with delta mean a change of vitamin D level was 2.92 ±7.29 ng/mL over three months in comparison to the insignificant change in oral cholecalciferol group. Additionally there was a significant increase in the mean of serum calcium in comparison to oral cholecalciferol group, while we found a statistically significant decrease in alkaline phosphatase level in both groups too (P&lt;0.05). The mean of iPTH levels was reduced significantly with IM cholecalciferol dose (1064.00 ± 787.60 to 609.9 ± 551.41 pg/mL; P&lt;0.05). Conclusion: Intramuscular cholecalciferol dose is more effective at increasing 25(OH) D levels in dialysis patients than oral supplementation, achieves more increase in serum calcium and reduce iPTH levels. However, the longer duration of treatment is required to achieve recommended levels of vitamin D and suppress high iPTH levels.

MO753RELATIONSHIP BETWEEN MINERAL BONE DISEASE AND ATHEROSCLEROSIS IN NON-DIABETIC PERITONEAL DIALYSIS PATIENTS

Abstract Background and Aims The term chronic kidney disease-mineral bone disorder has the role of highlighting that the disturbed mineral and bone metabolism is a major contributor to vascular calcification and finally cardiovascular disease in chronic kidney disease (CKD), especially in hemodialysis. This relationship was less studied in peritoneal dialysis (PD). The aim of the present study was to evaluate the impact of metabolic bone disorder (MBD) on symptomatic atherosclerosis (stable angina SA, acute coronary syndrome ACS, ischemic stroke, peripheral artery disease PAD) in non-diabetic PD patients. We choose to exclude diabetic patients since they are already at increased risk for atherosclerosis. Method We performed a prospective study in non-diabetic population of patients in stable PD programme for at least 6 months. We analysed clinical and biological parameters of calcium-phosphate metabolism (calcemia Ca, phosphatemia P, CaxP product, intact parathormone iPTH), presence of atherosclerotic disease and we performed carotid ultrasound for measurement of intima media thickness (IMT) as a marker for subclinic atherosclerosis. Independent risk factors for atherosclerotic disease were identified by multivariate analysis through logistic regression using IBM SPSS ver. 20.0. Results 246 consecutive non-diabetic PD patients (pts) were included (128M, 118F), mean age 56.3 + 15.7 years (20-85), with a follow up of 6.5±1.1 years. 19 pts (7.7%) had calcemia (Ca)&amp;gt;10.2 mg/dl, no patient had a Ca&amp;lt;8.2 mg/dl, 127 pts (51.6%) had phosphatemia (P)&amp;gt;5.5 mg/dl, 45 pts (18.3%) had CaxtaP product&amp;gt;55 mg2/dl2, 68 pts (27.6%) had iPTH&amp;lt;150 pg/ml, 95 pts (38.6%) had iPTH&amp;gt;300 pg/ml. We found a weak positive correlation between IMT and Ca (r=0.283, p=0.005); pts with iPTH&amp;lt;150 pg/ml and those with iPTH&amp;gt;300 pg/ml had a higher risk of increased IMT compared to pts with iPTH 150-300 pg/ml (OR 4.1, p=0.009, for iPTH&amp;lt;150 pg/ml, respectively OR 3.4, p=0.01 for iPTH&amp;gt;300 pg/ml). Pts with atherosclerotic disease had significantly higher P and CaxP, without differences regarding Ca and iPTH (Table 1). An iPTH&amp;lt;150 pg/ml was a risk factor for SA, ACS and PAD, while iPTH&amp;gt;300 pg/ml was a risk factor for SA and ACS (Table 2). We perfomed multivariate analysis to identify independent risk factors for SA, ACS, stroke and PAD by entering in the analysis the factors identified in univariate analysis to be significantly associated with different manifestations of atherosclerosis. Among independent risk factors identified for atherosclerotic disease, iPTH&amp;lt;150 pg/ml was risk factor for SA (adjusted OR 11.5, p=0.007) and ACS (adjusted OR 221.4, p=0.01), iPTH&amp;gt;300 pg/ml was risk factor for ACS (adjusted OR 5.2, p=0.03), CaxP &amp;gt;55 mg2/dl2 was risk factor for ACS (adjusted OR 33.5, p=0.02) and ischemic stroke (adjusted OR 4.4, p=0.01). No parameters of calcium-phosphate metabolism were identified as independent risk factors for PAD. Conclusion We found significant independent correlations between different parameters which characterize MBD and presence of symptomatic atherosclerosis in non-diabetic PD pts. The most important risk factors identified were abnormally low or high iPTH level, and elevated CaxP. The most striking result was the low iPTH associated with SA and especially ACS, suggesting that an adynamic bone is incapable to buffer the serum calcium and phosphate, thus increasing the risk of vascular calcifications. Future studies may address the issue whether correction of these parameters may be associated with attenuation of atherosclerotic disease in this population.

A Case of Pseudohypoparathyroidism Type 1b in Pregnancy

Introduction: Pseudohypoparathyroidism (PHP) type 1b is characterized by target organ resistance to PTH leading to hypocalcemia and hyperphosphatemia in the setting of elevated PTH due to abnormal imprinting that affects the regulatory elements of GNAS1. It poses challenges in management during pregnancy and lactation. We report the case of a patient who was diagnosed with PHP type 1b while pregnant. Case Presentation: A 30 year old woman, 16 weeks pregnant was referred for the evaluation of hypocalcemia. She had a history of traumatic fracture of her lower extremity and hypothyroidism treated with levothyroxine. She was noted to have hypocalcemia 1 year prior during routine labs. Family history was significant for hypothyroidism in her sister. On physical examination, she did not have phenotypic features of Albright hereditary osteodystrophy except for short stature. Before pregnancy her labs were significant for Ca 8.1 mg/dL(8.6–10.2), iCa 4.2 mg/dL(4.8–5.6), iPTH 289 pg/mL (14–64), creatinine 0.6 mg/dL(0.8–1.2), 25 vitamin D 22 ng/mL and 24 hr urine Ca 80 mg/24 hr (65-250mg). She was started on a combination of calcium citrate and carbonate 600 mg daily and vitamin D 1000 units daily. Labs while pregnant showed Ca 8.1 mg/dL, iCa 4.1 mg/dL, iPTH 184 pg/mL, PO4 4.9 mg/dL(2.5–3.5), 1,25 Vitamin D 53 pg/mL(18–72) and 25 Vitamin D 38 ng/mL. She had mild paresthesia and muscle cramps. Calcium supplements were increased to 1800 mg daily. While the urine Ca increased to 315 mg/24 hr, other biochemical parameters did not improve. Given her low Ca, high iPTH, high PO4, normal GFR and 25 vitamin D, PHP was suspected. Genetic testing showed loss of methylation at GNAS locus down to 5% (NL >43%) Diagnosis of PHP type 1b was made. Her Ca decreased the next months to a nadir of 7.9 mg/dL despite increased doses of calcium up to 1200 mg BID. Calcitriol 0.25 mcg BID was added. The rest of her pregnancy the serum Ca stayed between 8.1–8.6 mg/dL. She delivered a boy. At birth his Ca was 8.0 mg/ dL and PTH 81pg/mL. Genetic testing showed 41% methylation of GNAS. While breast feeding her Ca was 9.4 mg/dL, her calcitriol and calcium supplements were decreased. She continues to do well on calcium 630 mg daily and calcitriol 0.25 mcg daily with serum Ca between 8.5–8.8 mg/dL. Conclusion: The literature on PHP in pregnancy is scarce due to its rarity and the management is challenging due to altered calcium and vitamin D metabolism during pregnancy and lactation. The fetus draws calcium from maternal circulation and predisposes mother to hypocalcemia. Some patients may become normocalcemic during pregnancy due to placental secretion of 1,25 Vitamin D and PTHrp. There is also increased demand for calcium with lactation. There are genetic implications on the baby as it is inherited in an autosomal dominant mode. It is important to monitor calcium levels closely as there are multiple factors that could influence calcium metabolism in pregnancy.