Associations of calcium, phosphate and intact parathyroid hormone levels with mortality, residual kidney function and technical failure among patients on peritoneal dialysis
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PROVIDER: S-EPMC10616493 | biostudies-literature | 2023 Sep
REPOSITORIES: biostudies-literature
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Project description:ObjectiveSarcopenia is highly prevalent in patients undergoing peritoneal dialysis (PD), contributing to adverse clinical outcomes. Animal models suggest that parathyroid hormone (PTH) induces muscle wasting through adipose tissue browning. However, the relationship between PTH dysregulation and sarcopenia in the PD population remains unclear. Thus, we aimed to explore the association between serum intact PTH levels and sarcopenia in PD patients.MethodsWe conducted a cross-sectional analysis using data from the Tzu-Chi PD cohort, comprising 186 PD patients with a mean age of 57.5 ± 14.1 years. Basic information, comorbidities, serum intact PTH levels, and other biochemical data were retrieved. Atherosclerotic cardiovascular disease (ASCVD) includes any history of coronary artery disease, myocardial infarction, peripheral arterial disease, and stroke. All patients were evaluated for appendicular skeletal muscle mass (ASM) using the Body Composition Monitor (BCM), handgrip strength, and 6-m usual gait speed. Sarcopenia was defined based on the consensus of the Asian Working Group for Sarcopenia 2019. Relative over-hydration (OH) was also assessed using BCM.ResultsThe overall prevalence of sarcopenia was 38.2%. Across three groups of intact PTH levels (<150 pg/mL, 150-300 pg/mL, and >300 pg/mL), the prevalence rates of sarcopenia were 29.7, 36.4, and 46.2%, respectively (p for trend = 0.044). In the unadjusted model, age, ASCVD, subjective global assessment score, body mass index, relative OH, serum albumin, creatinine, phosphorus, and log-transformed intact PTH levels were significantly associated with sarcopenia. After full adjustment for all above factors, age (odds ratio [OR] = 1.04, 95% confidence interval [CI] = 1.00-1.08), ASCVD (OR = 4.12, 95% CI = 1.34-12.65), BMI (OR = 0.51, 95% CI = 0.41-0.64), relative OH (OR = 1.04, 95% CI = 1.00-1.07), log-transformed intact PTH levels (OR = 3.72, 95% CI = 1.51-9.14) were independently associated sarcopenia among PD patients.ConclusionAmong PD patients, elevated serum intact PTH levels are independently associated with sarcopenia. Further longitudinal studies are warranted to confirm their causal relationship.
| S-EPMC11521897 | biostudies-literature
Project description:Identifying modifiable risk factors of peritoneal dialysis (PD)-related peritonitis is of clinical importance in patient care. Mineral bone disease (MBD) has been associated with mortality and morbidity in end-stage kidney disease (ESKD) patients. However, its influence on PD related peritonitis due to altered host immunity remains elusive. This study investigated whether abnormal biomarkers of MBD are associated with the development of peritonitis in patients undergoing maintenance PD. We conducted a retrospective observational cohort study, analysing data derived from a nationwide dialysis registry database in Taiwan, from 2005 to 2012. A total of 5750 ESKD patients commencing PD therapy during this period were enrolled and followed up to 60 months or by the end of the study period. The patients were stratified based on their baseline serum parathyroid hormone (PTH) levels, calcium (Ca) levels or phosphorus (P) levels, respectively or in combinations. The primary outcome was the occurrence of first episode of peritonitis, and patient outcomes such as deaths, transfer to haemodialysis or receiving renal transplantation were censored. Peritonitis-free survival and the influence of PTH, Ca, P (individual or in combination) on the peritonitis occurrence were analysed. A total of 5750 PD patients was enrolled. Of them, 1611 patients experienced their first episode of peritonitis during the study period. Patients with low PTH, high Ca or low P levels, respectively or in combination, had the lowest peritonitis-free survival. After adjusting for age, sex and serum albumin levels, we found that the combinations of low PTH levels with either high Ca levels or low/normal P levels were significant risk factors of developing peritonitis. Abnormal mineral bone metabolism in maintenance PD patients with low serum PTH levels, in combination with either high Ca levels or low/normal P levels, could be novel risk factors of PD-related peritonitis.
| S-EPMC7806837 | biostudies-literature
Project description:BackgroundContinuous ambulatory peritoneal dialysis (CAPD) patients have a high incidence of stroke and commonly have increased parathyroid hormone levels and vitamin D insufficiency. We seek to investigate the incidence of stroke and the role of parathyroid hormone and vitamin D supplementation in stroke risk among CAPD patients.MethodsThis study employed a retrospective design. We enrolled a Chinese cohort of 980 CAPD patients who were routinely followed in our department. The demographic and clinical data were recorded at the time of initial CAPD and during follow-up. The included patients were separated into non-stroke and stroke groups. The effects of parathyroid hormone and vitamin D supplementation on stroke in CAPD patients was evaluated. The primary endpoint is defined as the first occurrence of stroke, and composite endpoint events are defined as death or switch to hemodialysis during follow-up.ResultsA total of 757 eligible CAPD patients with a mean follow-up time of 54.7 (standard deviation, 33) months were included in the study. The median incidence of stroke among our CAPD patients was 18.9 (interquartile range, 15.7-22.1) per 1000 person-years. A significant nonlinear correlation between baseline iPTH and hazard of stroke (p-value of linear association = 0.2 and nonlinear association = 0.002) was observed in our univariate Cox regression analysis, and low baseline iPTH levels (≤150 pg/ml) were associated with an increased cumulative hazard of stroke. Multivariate Cox regression analysis indicated a significant interaction effect between age and iPTH after adjusting for other confounders. Vitamin D supplementation during follow-up was a predictive factor for stroke in our cohort.ConclusionsCAPD patients suffered a high risk of stroke, and lower iPTH levels were significantly correlated with an increased risk of stroke. Nevertheless, vitamin D supplementation may reduce the risk of stroke in these patients.
| S-EPMC7236177 | biostudies-literature
Project description:Mineral and bone disorder (MBD) is observed universally in patients with chronic kidney disease (CKD). Detrimental MBD-related skeletal changes include increased prevalence of fracture, cardiovascular disease, and mortality. MicroRNAs (miRNAs) have been identified as useful biomarkers in various diseases, and the aim of this study was to identify miRNAs associated with parathyroid hormone level in peritoneal dialysis (PD) patients. Fifty-two PD patients were enrolled and grouped by their intact parathyroid hormone (iPTH) level; 11 patients had low iPTH (<150 pg/mL) and 41 patients had high iPTH (≥150 pg/mL). Total RNA was extracted from whole blood samples. Total RNA from 15 patients (7 and 8 patients in the low and high iPTH groups, respectively) underwent miRNA microarray analysis, and three differentially upregulated (>2-fold change) miRNAs previously associated with human disease were selected for real-time quantitative PCR (qPCR) analysis. Interaction analyses between miRNAs and genes were performed by using TargetScan and the KEGG pathway database. Microarray results revealed 165 miRNAs were differentially expressed between patients with high iPTH levels and low iPTH levels. Of those miRNAs, 81 were upregulated and 84 were downregulated in patients with high iPTH levels. Expression levels of miR-1299, miR-3680-5p, and miR-548b-5p (previously associated with human disease) in 52 patients were analyzed by using qPCR. MiR-3680-5p was differentially expressed in low and high iPTH patients (P < 0.05). The predicted target genes of miR-3680-5p were USP6, USP32, USP46, and DLT, which are involved in the ubiquitin proteolysis pathway. This pathway has roles in PTH and parathyroid hormone related protein degradation and proteolysis. The mechanisms involved in the associations among low PTH, adynamic bone disease, miR-3680-5p, and the target genes should be explored further in order to elucidate their roles in CKD-MBD development.
| S-EPMC5289431 | biostudies-literature
Project description:In renal failure, hyperphosphatemia is common and correlates with increased mortality making phosphate removal a key priority for dialysis therapy. We investigated phosphate clearance, removal and serum level, and factors associated with phosphate control in patients undergoing continuous ambulatory (CAPD), continuous cyclic (CCPD) and automated (APD) peritoneal dialysis (PD). In 154 prevalent PD patients (mean age 53.2 ± 17.6 year, 59% men, 47% anuric), 196 daily collections of urine and 368 collections of dialysate were evaluated in terms of renal, peritoneal and total (renal plus peritoneal) phosphorus removal (g/week), phosphate and creatinine clearances (L/week) and urea KT/V. Dialytic removal of phosphorus was lower in APD (1.34 ± 0.62 g/week) than in CAPD (1.89 ± 0.73 g/week) and CCPD (1.91 ± 0.63 g/week) patients; concomitantly, serum phosphorus was higher in APD than in CAPD (5.55 ± 1.61 vs. 4.84 ± 1.23 mg/dL; p < 0.05). Peritoneal and total phosphate clearances correlated with peritoneal (rho = 0.93) and total (rho = 0.85) creatinine clearances (p < 0.001) but less with peritoneal and total urea KT/V (rho = 0.60 and rho = 0.65, respectively, p < 0.001). Phosphate removal, clearance and serum levels differed between PD modalities. CAPD was associated with higher peritoneal removal and lower serum level of phosphate than APD.
| S-EPMC7566511 | biostudies-literature
Project description:Extracellular phosphate regulates its own renal excretion by eliciting concentration-dependent secretion of parathyroid hormone (PTH). However, the phosphate-sensing mechanism remains unknown and requires elucidation for understanding the aetiology of secondary hyperparathyroidism in chronic kidney disease (CKD). The calcium-sensing receptor (CaSR) is the main controller of PTH secretion and here we show that raising phosphate concentration within the pathophysiologic range for CKD significantly inhibits CaSR activity via non-competitive antagonism. Mutation of residue R62 in anion binding site-1 abolishes phosphate-induced inhibition of CaSR. Further, pathophysiologic phosphate concentrations elicit rapid and reversible increases in PTH secretion from freshly-isolated human parathyroid cells consistent with a receptor-mediated action. The same effect is seen in wild-type murine parathyroid glands, but not in CaSR knockout glands. By sensing moderate changes in extracellular phosphate concentration, the CaSR represents a phosphate sensor in the parathyroid gland, explaining the stimulatory effect of phosphate on PTH secretion.
| S-EPMC6795806 | biostudies-literature
Project description:BackgroundThe number of patients ⩾65 years who require maintenance hemodialysis (MHD) is increasing. Although reduced bone turnover in older patients receiving hemodialysis, as reflected by lower serum intact parathyroid hormone (iPTH) and phosphate (P) levels, has been reported, focus on the association between abnormal bone metabolism and the risk of death in older patients receiving MHD has been limited.MethodsWe retrospectively examined data from the Beijing Hemodialysis Quality Control and Improvement Center for 1410 older patients who underwent hemodialysis from 1 January 2012 to 31 December 2016. Baseline, time-dependent (TD) Cox proportional hazards models and Kaplan-Meier analyses were used to evaluate the association between the markers of mineral and bone disorder (MBD) [calcium (Ca), P, and iPTH] and survival. The Kidney Disease: Improving Global Outcomes (KDIGO) target ranges were included as reference values.ResultsSerum P levels >2.49 mmol/l increased the risk of all-cause death [hazard ratio (HR): 1.46; 95% confidence interval (CI): 1.04-2.07; p = 0.030] and cardiovascular death (HR: 2.01; 95%CI: 1.21-3.34; p = 0.007); iPTH levels >600 pg/ml increased the risk of cardiovascular death (HR: 1.95; 95%CI: 1.20-3.15; p = 0.007). Baseline results and TD Cox analyses were similar. All three MBD parameters were within the respective target ranges at least once during the follow-up period in 399 (28.3%) patients, and these patients had better survival rates than those who achieved two of the three target ranges (715/1410 patients; 50.7%); those who achieved one or no target range (296/1410; 21.0%) had the lowest survival rate (all-cause death: log-rank chi square = 83.96, p < 0.001; cardiovascular death: log-rank chi square = 47.06, p < 0.001).ConclusionOlder patients undergoing MHD who achieved the KDIGO target levels for any two or three MBD parameters had lower risks of all-cause and cardiovascular death.
| S-EPMC8246503 | biostudies-literature
Project description:ObjectiveTo examine independent associations of serum 25-hydroxyvitamin D (25(OH)D), parathyroid hormone (PTH) and calcium with a range of cardiovascular risk factors in adolescents.DesignCross-sectional population-based study.SettingA nationally representative sample of the US adolescent population.ParticipantsHealthy adolescents (aged 12-19) participating in the National Health and Nutrition Examination Survey (NHANES) between 2001 and 2006. Numbers varied between 740 and 5609 for given exposure and outcome associations.Main outcome measuresSystolic blood pressure (SBP), diastolic blood pressure (DBP), lipids (triglycerides, low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C)), fasting insulin and glucose, postload glucose and glycohaemoglobin (HbA1c).Results25(OH)D was inversely associated with SBP (-0.068 standard deviations (SD), 95% CI -0.118 to -0.018), and positively associated with HDL-C (0.101; 0.040 to 0.162) and HbA1c (0.073; 0.021 to 0.125) after adjustment for gender, age, ethnicity, socioeconomic status and waist circumference. In adjusted models, PTH was inversely associated with triglycerides (-0.115; -0.188 to -0.042) and LDL-C (-0.133; -0.207 to -0.060). In adjusted models, calcium was positively associated with fasting insulin (0.110; 0.060 to 0.160), postload glucose (0.116; 0.000 to 0.232), HbA1c (0.079; 0.035 to 0.123), triglycerides (0.182; 0.122 to 0.242), HDL-C (0.049; 0.010 to 0.088) and LDL-C (0.137; 0.080 to 0.195). The associations of each exposure with risk factors remained after mutual adjustment for each other.ConclusionHigher calcium levels might be a more important predictor of increased cardiovascular risk in adolescents than lower 25(OH)D levels or PTH levels, but the findings require replication in additional studies and examination in prospective studies.
| S-EPMC3931194 | biostudies-literature
Project description:Although echocardiograms are often performed when peritoneal dialysis is started, associations between commonly reported findings and prospective changes in renal function remain understudied. Ninety-nine of 101 patients in the Trio Trial had transthoracic echocardiograms within 6 months of dialysis initiation, and measurements of residual renal function every six weeks for up to two years. Generalized mixed modelling linear regression in STATA was used to examine associations between left atrial size, left ventricular hypertrophy, left ventricular ejection fraction, right ventricular systolic pressure, and left valvular calcification with subsequent slopes in renal function. After echocardiography (performed a median of 16 days following peritoneal dialysis initiation) right ventricular systolic pressure was associated with faster, while declining left ventricular ejection fraction and valvular calcification were associated with slower declines in residual renal function. Future studies could be conducted to confirm these findings, and identify pathophysiological mechanisms.
| S-EPMC6895151 | biostudies-literature
Project description:BACKGROUND AND OBJECTIVES:Residual kidney function contributes to the clearance of antibiotics excreted by the kidneys, lowering the antibiotic concentration, which may adversely affect the treatment of peritoneal dialysis-associated peritonitis. The objective of our study was to examine the relationship between residual kidneyfunction and peritonitis treatment outcomes. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS:Our study included 181 participants who experienced 339 episodes of Gram-positive, Gram-negative, and culture-negative peritoneal dialysis-associated peritonitis at a single centerfrom 2003 to 2010. Episodes were categorized according to participants' urinary creatinine clearance (0, >0-5, and >5 ml/min). The data were analyzed using generalized estimating equation models to determine the covariate-adjusted association between urinary creatinine clearance and treatment failure (defined as relapse or recurrent peritonitis episodes, peritoneal catheter removal, or death from any cause during peritonitis treatment). RESULTS:Among episodes of peritonitis due to Gram-positive organisms or culture-negative infections, those experienced by participants with urinary creatinine clearance >5 ml/min had significantly higher odds of treatment failure than episodes experienced by anuric participants (27 of 80 versus 20 of 119 episodes resulting in treatment failure for creatinine clearance >5 versus 0 ml/min; odds ratio, 6.80; 95% confidence interval, 2.37 to 19.6). Episodes experienced by participants with creatinine clearance >0-5 ml/min also had significantly higher odds of treatment failure than episodes experienced by anuric participants (14 of 64 episodes resulting in treatment failure for creatinine clearance >0-5 ml/min; odds ratio, 2.87; 95% confidence interval, 1.12 to 7.35). The odds of relapse and recurrent peritonitis among participants with creatinine clearance >5 ml/min was also significantly higher compared with in anuric participants (17 of 80 versus 12 of 119 episodes resulting in relapse and recurrence for creatinine clearance >5 versus 0 ml/min; odds ratio, 6.76; 95% confidence interval, 1.90 to 23.8). Among participants with Gram-negative peritonitis, creatinine clearance was significantly associated with neither treatment failure nor relapse and recurrent peritonitis. CONCLUSIONS:Residual kidney function as measured by greater urinary creatinine clearance was associated with treatment failure among participants with Gram-positive and culture-negative peritonitis.
| S-EPMC5718262 | biostudies-literature