Dataset Information

Is there an association between elevated or low serum levels of phosphorus, parathyroid hormone, and calcium and mortality in patients with end stage renal disease? A meta-analysis.

ABSTRACT:

Background

Biochemical markers of altered mineral metabolism have been associated with increased mortality in end stage renal disease patients. Several studies have demonstrated non-linear (U-shaped or J-shaped) associations between these minerals and mortality, though many researchers have assumed linear relationships in their statistical modeling. This analysis synthesizes the non-linear relationships across studies.

Methods

We updated a prior systematic review through 2010. Studies included adults receiving dialysis and reported categorical data for calcium, phosphorus, and/or parathyroid hormone (PTH) together with all-cause mortality. We performed 2 separate meta-analyses to compare higher-than-referent levels vs referent and lower-than-referent levels vs referent levels.

Results

A literature review showed that when a linear relationship between the minerals and mortality was assumed, the estimated associations were more likely to be smaller or non-significant compared to non-linear models. In the meta-analyses, higher-than-referent levels of phosphorus (4 studies, RR = 1.20, 95% CI = 1.15-1.25), calcium (3 studies, RR = 1.10, 95% CI = 1.05-1.14), and PTH (5 studies, RR = 1.11, 95% CI = 1.07-1.16) were significantly associated with increased mortality. Although no significant associations between relatively low phosphorus or PTH and mortality were observed, a protective effect was observed for lower-than-referent calcium (RR = 0.86, 95% CI = 0.83-0.89).

Conclusions

Higher-than-referent levels of PTH, calcium, and phosphorus in dialysis patients were associated with increased mortality risk in a selection of observational studies suitable for meta-analysis of non-linear relationships. Findings were less consistent for lower-than-referent values. Future analyses should incorporate the non-linear relationships between the minerals and mortality to obtain accurate effect estimates.

SUBMITTER: Natoli JL

PROVIDER: S-EPMC3658973 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

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: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:BackgroundPeritoneal dialysis (PD) is an easily implementable dialysis modality in end-stage renal disease (ESRD). PD may improve access to renal replacement therapy in low- and middle-income countries; however, these countries have a higher prevalence of protein-energy wasting in patients and poorer socioeconomic conditions. We evaluated the effects of HIV infection on serum albumin levels in ESRD patients starting continuous ambulatory PD (CAPD) and mortality outcomes.MethodsWe conducted a single-center prospective cohort study of consecutive incident CAPD patients recruited from two hospitals in Durban, South Africa, from September 2012 to February 2015. Seventy HIV-negative and 70 HIV-positive ESRD patients were followed monthly for serum albumin levels and mortality events during the first 18 months of CAPD therapy.ResultsThe HIV-positive cohort recorded 28 deaths (40%) among patients with a functional CAPD catheter at 18 months and 13 deaths (18.6%) in the HIV-negative cohort (p = 0.005). The mean serum albumin levels were lower in the HIV-positive cohort than in the HIV-negative cohort during the 18-month follow-up. The mean difference in serum albumin levels between the two cohorts was 4.24 g/L (95% confidence interval [CI] 2.02-6.46, p<0.001) at baseline and 3.99 g/L (95% CI 1.19-6.79, p = 0.006) at 18 months. HIV-positive status (adjusted regression coefficient -2.84, CI -5.00--0.67, p = 0.011), diabetes (adjusted coefficient -2.85; CI, -5.58--0.12; p = 0.041), and serum C-reactive protein and blood hemoglobin levels were independent predictors of serum albumin levels on multivariable linear regression. Baseline serum albumin <25 g/L (subdistribution-hazard ratio [SHR] 13.06, 95% CI 3.09-55.14, p<0.001) and CD4+ cell count <200 cells/?L (SHR 3.2, CI 1.38-7.45, p = 0.007) were independent predictors of mortality in our competing risk model.ConclusionsHIV infection can adversely affect serum albumin levels in ESRD patients managed with CAPD, while low baseline serum albumin levels and impaired immunity reliably predict mortality.

Project description:OBJECTIVE:Hyperphosphatemia is common in end-stage renal disease and associates with mortality. Phosphate binders reduce serum phosphorus levels; however, adherence is often poor. This pilot study aims to assess patients' self-motivation to adhere to phosphate binders, its association with phosphorus control, and potential differences by race. DESIGN AND METHODS:Cross sectional design. Subjects were enrolled from one academic medical center dialysis practice from July to November 2012. Self-motivation to adhere to phosphate binders was assessed with the autonomous regulation (AR) scale (range: 1-7) and self-reported medication adherence with the Morisky Medication Adherence Scale. Linear regression models adjusting for age, sex, health literacy, and medication adherence were applied to determine associations with serum phosphorus level, including any evidence of interaction by race. RESULTS:Among 100 participants, mean age was 51 years (±15 years), 53% were male, 72% were non-white, 89% received hemodialysis, and mean serum phosphorus level was 5.7 ± 1.6 mg/dL. More than half (57%) reported the maximum AR score (7). Higher AR scores were noted in those reporting better health overall (P = .001) and those with higher health literacy (P = .01). AR score correlated with better medication adherence (r = 0.22; P = .02), and medication adherence was negatively associated with serum phosphorus (r = -0.40; P < .001). In subgroup analysis among non-whites, higher AR scores correlated with lower serum phosphorus (high vs lower AR score: 5.55 [1.5] vs 6.96 [2.2]; P = .01). Associations between AR score (? 95% confidence interval: -0.37 [-0.73 to -0.01]; P = .04), medication adherence (? 95% confidence interval: -0.25 [-0.42 to -0.07]; P = .01), and serum phosphorus persisted in adjusted analyses. CONCLUSIONS:Self-motivation was associated with phosphate binder adherence and phosphorus control, and this differed by race. Additional research is needed to determine if personalized, culturally sensitive strategies to understand and overcome motivational barriers may optimize mineral bone health in end-stage renal disease.