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Effects of genetic variants on serum parathyroid hormone in hyperparathyroidism and end-stage renal disease patients: A systematic review and meta-analysis.

ABSTRACT: BACKGROUND:Parathyroid hormone (PTH) is one of the principal regulators of calcium homeostasis, crucial for normal functioning of the kidneys, bones, heart, and nervous system. Different pathologic conditions can affect serum PTH level resulting in hyperparathyroidism or hypoparathyroidism. Our study assessed the association of previously reported polymorphisms with the level of PTH (expressed in pg/mL) among individuals with different pathologic conditions affecting PTH level. METHODS:We searched Web of Science, MEDLINE, and Scopus to identify relevant articles published up to July 2017. The search yielded 6967 publications of which 44 fulfilled the inclusion criteria. We conducted meta-analyses for calcium-sensing receptor gene (CaSR) rs1801725 polymorphism in patients with primary hyperparathyroidism and vitamin D receptor gene (VDR) rs1544410 polymorphism in patients with end-stage renal disease (ESRD). RESULTS:None of the polymorphisms were significantly associated with PTH levels in the overall population. In subgroup analysis by ethnicity for VDR rs1544410 gene polymorphism, we found significant differences under dominant model (SMD: -0.18 [-0.32, -0.05], P?

SUBMITTER: Matana A

PROVIDER: S-EPMC6392899 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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Effects of genetic variants on serum parathyroid hormone in hyperparathyroidism and end-stage renal disease patients: A systematic review and meta-analysis.

Matana Antonela A Popović Marijana M Torlak Vesela V Punda Ante A Barbalić Maja M Zemunik Tatijana T

Medicine 20180501 21

<h4>Background</h4>Parathyroid hormone (PTH) is one of the principal regulators of calcium homeostasis, crucial for normal functioning of the kidneys, bones, heart, and nervous system. Different pathologic conditions can affect serum PTH level resulting in hyperparathyroidism or hypoparathyroidism. Our study assessed the association of previously reported polymorphisms with the level of PTH (expressed in pg/mL) among individuals with different pathologic conditions affecting PTH level.<h4>Method ...[more]

PMID: 29794776

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Project description:Elevated serum phosphorus (P) levels have been linked to increased morbidity and mortality in dialysis patients with secondary hyperparathyroidism (SHPT) but may be difficult to control if parathyroid hormone (PTH) is persistently elevated. We conducted a post hoc analysis of data from an earlier interventional study (OPTIMA) to explore the relationship between PTH control and serum P.The OPTIMA study randomized dialysis patients with intact PTH (iPTH) 300-799 pg/mL to receive conventional care alone (vitamin D and/or phosphate binders [PB]; n=184) or a cinacalcet-based regimen (n=368). For patients randomized to conventional care, investigators were allowed flexibility in using a non-cinacalcet regimen (with no specific criteria for vitamin D analogue dosage) to attain KDOQI™ targets for iPTH, P, Ca and Ca x P. For those assigned to the cinacalcet-based regimen, dosages of cinacalcet, vitamin D sterols, and PB were optimized over the first 16 weeks of the study, using a predefined treatment algorithm. The present analysis examined achievement of serum P targets (? 4.5 and ? 5.5 mg/dL) in relation to achievement of iPTH ? 300 pg/mL during the efficacy assessment phase (EAP; weeks 17-23).Patients who achieved iPTH ? 300 pg/mL (or a reduction of ? 30% from baseline) were more likely to achieve serum P targets than those who did not, regardless of treatment group. Of those who did achieve iPTH ? 300 pg/mL, 43% achieved P ? 4.5 mg/dL and 70% achieved P ? 5.5 mg/dL, versus 21% and 46% of those who did not achieve iPTH ? 300 pg/mL. Doses of PB tended to be higher in patients not achieving serum P targets. Patients receiving cinacalcet were more likely to achieve iPTH ? 300 pg/mL than those receiving conventional care (73% vs 23% of patients). Logistic regression analysis identified lower baseline P, no PB use at baseline and cinacalcet treatment to be predictors of achieving P ? 4.5 mg/dL during EAP in patients above this threshold at baseline.This post hoc analysis found that control of serum P in dialysis patients was better when serum PTH levels were lowered effectively, regardless of treatment received.Clinicaltrials.gov identifier NCT00110890.

Project description:The risk of vertebral fracture is unclear in end-stage renal disease. We report a high vertebral fracture prevalence and incidence in transplantation-eligible patients on dialysis, suggesting that these patients may benefit from radiographic screening for vertebral fractures. Parathyroid hormone had a U-shaped association with vertebral fracture risk.IntroductionVertebral fractures are often overlooked, but even undiagnosed vertebral fractures negatively impact physical functioning, quality of life, and mortality. The risk of vertebral fractures in end-stage renal disease (ESRD) patients is unclear, and parathyroid hormone (PTH) might play a role in the development of vertebral fractures. We therefore determined vertebral fracture prevalence and incidence in ESRD patients and assessed associations of vertebral trabecular bone mineral density (BMD) and PTH with vertebral fracture.MethodsIn 146 transplantation-eligible patients on dialysis, we determined vertebral fractures on lateral chest radiographs, which image the thoracic and upper lumbar spine. We determined incident vertebral fractures in 70 patients with follow-up radiographs (23 received a kidney transplant) after median 1.8 years. Vertebral trabecular BMD was measured with computed tomography, and PTH measured with 2-site immunoassays, categorized in tertiles with the middle tertile as reference. We used Poisson regression to assess associations of vertebral trabecular BMD and PTH with vertebral fracture.ResultsMean age of the study population was 52 ± 13 years, and 98 (67%) were male. Median dialysis duration was 26 (IQR 13-55) months. Vertebral fractures were present in 50/146 patients (34%) and incident vertebral fractures occurred in 20/70 patients (29%). Vertebral trabecular BMD was not associated with vertebral fracture prevalence (relative risk 0.97, 95% CI 0.89 to 1.04). For the lowest PTH tertile (< 11 pmol/L), the relative risk of vertebral fracture was greater although not significant (2.28, 95% CI 0.97 to 5.97) and was significantly greater for the highest PTH tertile (≥ 30 pmol/L; 2.82, 95% CI 1.22 to 7.27) after adjustment for potential confounders.ConclusionsThe prevalence and incidence of vertebral fractures is high even in relatively young and healthy ESRD patients. Vertebral trabecular BMD is not associated with vertebral fracture, and the association of PTH with vertebral fracture risk appears U-shaped. Nevertheless, our study did not measure vertebral BMD using DXA and assessed vertebral fractures using lateral chest radiographs and not spine radiographs.

Project description:Persistent or recurrent renal hyperparathyroidism may occur after total parathyroidectomy and transcervical thymectomy with forearm autograft under continuous stimulation due to uremia. Parathyroid hormone (PTH) levels may reflect persistent or recurrent renal hyperparathyroidism because of the enlarged autografted parathyroid glands in the forearm or remnant parathyroid glands in the neck or mediastinum. Detailed imaging requires predictive localization of causative parathyroid glands. Casanova and simplified Casanova tests may be convenient. However, these methods require avascularization of the autografted forearm for >10 min with a tourniquet or Esmarch. The heavy pressure during avascularization can be incredibly painful and result in nerve damage. An easier method that minimizes the burden on patients in addition to predicting the localization of causative parathyroid glands was developed in this study. Ninety patients who underwent successful re-parathyroidectomy for persistent or recurrent renal hyperparathyroidism after parathyroidectomy between January 2000 and July 2019 were classified according to the localization of causative parathyroid glands (63 and 27 patients in the autografted forearm and the neck or mediastinum groups, respectively). Preoperatively, intact PTH levels were measured from bilateral forearm blood samples following a 5-min avascularization of the autografted forearm. Cutoff values of the intact PTH ratio (intact PTH level obtained from the non-autografted forearm before re-parathyroidectomy/intact PTH level obtained from the autografted forearm before re-parathyroidectomy) were investigated with receiver operating characteristic curves to localize the causative parathyroid glands. Intact PTH ratios of <0.310 with an area under the curve (AUC) of 0.913 (95% confidence interval [CI]: 0.856-0.970; P < 0.001) and >0.859 with an AUC 0.744 (95% CI: 0.587-0.901; P = 0.013) could predict causative parathyroid glands in the autografted forearm and the neck or mediastinum with diagnostic accuracies of 81.1% and 83.3%, respectively. Therefore, we propose that the intact PTH ratio is useful for predicting the localization of causative parathyroid glands for re-parathyroidectomy.

Project description:OBJECTIVE:Serum albumin is a marker of malnutrition and inflammation and has been demonstrated as a strong predictor of mortality in chronic kidney disease (CKD) and end-stage renal disease (ESRD) patients. Yet, whether serum albumin levels in late-stage CKD are associated with adverse outcomes after the transition to ESRD is unknown. We hypothesize that lower levels and a decline in serum albumin in late-stage CKD are associated with higher risk of mortality and hospitalization rates 1 year after transition to ESRD. DESIGN AND METHODS:This retrospective cohort study included 29,124 US veterans with advanced CKD transitioning to ESRD between 2007 and 2015. We evaluated the association of pre-ESRD (91 days before transition) serum albumin with 12-month post-ESRD all-cause, cardiovascular, and infection-related mortalities and hospitalization rates as well as the association of 1-year pre-ESRD albumin slope and 12-month post-ESRD mortality using hierarchical multivariable adjustments. RESULTS:There was a negative linear association between serum albumin and all-cause mortality, such that risk doubled (hazard ratio [HR]: 2.07, 95% confidence interval [CI]: 1.87, 2.28) for patients with the lowest serum albumin <2.8 g/dL (ref: ?4.0 g/dL) after full adjustment. A consistent relationship was observed between serum albumin and cardiovascular and infection-related mortality, and hospitalization outcomes. An increase in serum albumin of >0.25 g/dL/year was associated with reduced mortality risk (HR: 0.76, 95% CI: 0.63, 0.91) compared with a slight decline in albumin (ref: >-0.25 to 0 g/dL/year), whereas a decline more than 0.5 g/dL/year was associated with a 55% higher risk in mortality (HR: 1.55, 95% CI: 1.43, 1.68) in fully adjusted models. CONCLUSIONS:Lower pre-ESRD serum albumin was associated with higher post-ESRD all-cause, cardiovascular, and infection-related mortalities and hospitalization rates. Declining serum albumin levels in the pre-ESRD period were also associated with worse 12-month post-ESRD mortality.

Dataset Information

Effects of genetic variants on serum parathyroid hormone in hyperparathyroidism and end-stage renal disease patients: A systematic review and meta-analysis.

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Effects of genetic variants on serum parathyroid hormone in hyperparathyroidism and end-stage renal disease patients: A systematic review and meta-analysis.

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