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The association between parathyroid hormone and mortality in dialysis patients is modified by wasting.

Drechsler C, Krane V, Grootendorst DC, Ritz E, Winkler K, März W, Dekker F, Wanner C, German Diabetes and Dialysis Study Investigato - Nephrol. Dial. Transplant. (2009)

Bottom Line: Patients had a mean age of 66 +/- 8 years, and 54% were male.Patients in the highest PTH tertile had a 74% higher risk of death (HR(adj) 1.74, 95% CI 1.27-2.40) and a 49% higher risk of CVE (HR(adj) 1.49, 95% CI 1.05-2.11) compared to patients in the lowest PTH tertile.In contrast, no effect was found in patients with wasting.

View Article: PubMed Central - PubMed

Affiliation: Division of Nephrology, Department of Medicine, University of Würzburg, Germany. drechsler_c@medizin.uni-wuerzburg.de

ABSTRACT

Background: The association between parathyroid hormone (PTH) level and mortality in dialysis patients is controversial. We hypothesized that wasting, a common condition potentially related to adynamic bone disease, modifies the association of PTH with mortality and cardiovascular events (CVE), respectively.

Methods: We analysed data from 1255 diabetic haemodialysis patients, participating in the German Diabetes and Dialysis Study between 1998 and 2004. The patients were stratified by the presence or absence of wasting (albumin 3.8 g/dL; BMI 23 kg/m(2)). Using Cox regression analyses, we calculated the risks of (1) all-cause mortality and (2) CVE according to baseline PTH levels. All analyses were adjusted for age, sex, atorvastatin treatment, duration of dialysis, comorbidity, HbA1c, phosphate, calcium, blood pressure, haemoglobin and C-reactive protein.

Results: Patients had a mean age of 66 +/- 8 years, and 54% were male. Among patients without wasting (albumin >3.8 g/dL, n = 586), the risks of death and CVE during 4 years of follow-up significantly increased by 23% and 20% per unit increase in logPTH. Patients in the highest PTH tertile had a 74% higher risk of death (HR(adj) 1.74, 95% CI 1.27-2.40) and a 49% higher risk of CVE (HR(adj) 1.49, 95% CI 1.05-2.11) compared to patients in the lowest PTH tertile. In contrast, no effect was found in patients with wasting. Accordingly, additional analyses in strata of BMI showed that PTH significantly impacted on death and CVE [HR(logPTH)(adj) 1.15 and 1.14, respectively] only in patients without, but not in patients with, wasting.

Conclusions: Wasting modifies the association of PTH with adverse outcomes in diabetic dialysis patients. High PTH levels are of concern in the patients without wasting, while the effect of PTH on mortality is ified in the patients with wasting.

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Related in: MedlinePlus

Kaplan–Meier curves for the time to all-cause mortality in patients with wasting (albumin ≤3.8 g/dL, A) and patients without wasting (albumin >3.8 g/dL, B); patients were grouped into tertiles of parathyroid hormone levels with the lowest tertile (tertile 1) serving as the reference group.
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Figure 1: Kaplan–Meier curves for the time to all-cause mortality in patients with wasting (albumin ≤3.8 g/dL, A) and patients without wasting (albumin >3.8 g/dL, B); patients were grouped into tertiles of parathyroid hormone levels with the lowest tertile (tertile 1) serving as the reference group.

Mentions: Within the whole study population, the mortality risks for patients in the second or third PTH tertile were not materially different compared to the reference of patients in the lowest PTH tertile (adjusted HRTertile2 1.17, 95% CI 0.95–1.44; adjusted HRTertile3 1.19, 95% CI 0.96–1.47). Investigating the hypothesis of effect modification by wasting, the analyses on PTH and mortality were stratified by wasting as defined by baseline albumin levels. In patients without wasting (albumin >3.8 g/dL, n = 586), the absolute mortality rate during 4 years of follow-up was 15 per 100 person years (py). All-cause mortality increased stepwise with higher PTH levels: it was 11/100 py for patients in the lowest tertile with a PTH ≤46.3 pg/mL, 15/100 py in patients with a PTH between 46.3 and 106 pg/mL (second tertile) and 17/100 py in patients with a PTH >106 pg/mL (third tertile) (Figure 1B and Table 2). In unadjusted Cox regression analyses using PTH as a continuous variable, the relative risk of death increased significantly by 17% per unit increase in log-transformed PTH (HR 1.17, 95% CI 1.04–1.31). The association was even stronger in multivariate analyses with a 23% increase in mortality per unit increase in log-transformed PTH (HR 1.23, 95% CI 1.09–1.39). With multivariate Cox regression models using PTH as a categorical variable, patients in the second PTH tertile had a 37% higher risk of death compared to those in the lowest tertile. Patients with highest PTH levels (third tertile) had the highest mortality, being significantly increased by 74% as compared to patients in the lowest PTH tertile (Table 2). Similar results were found in additional analyses using a BMI >23 kg/m2 to define the absence of wasting. All-cause mortality significantly rose by 15% per unit increase in log-transformed PTH in patients without wasting. In contrast, in patients with the disease state expectedly showing a high incidence of death (the absolute mortality rate was 21/100 py), no association of PTH with mortality was found: death rates were similar across the tertiles of PTH, both in the analyses using albumin and BMI for the definition of wasting.


The association between parathyroid hormone and mortality in dialysis patients is modified by wasting.

Drechsler C, Krane V, Grootendorst DC, Ritz E, Winkler K, März W, Dekker F, Wanner C, German Diabetes and Dialysis Study Investigato - Nephrol. Dial. Transplant. (2009)

Kaplan–Meier curves for the time to all-cause mortality in patients with wasting (albumin ≤3.8 g/dL, A) and patients without wasting (albumin >3.8 g/dL, B); patients were grouped into tertiles of parathyroid hormone levels with the lowest tertile (tertile 1) serving as the reference group.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC2747498&req=5

Figure 1: Kaplan–Meier curves for the time to all-cause mortality in patients with wasting (albumin ≤3.8 g/dL, A) and patients without wasting (albumin >3.8 g/dL, B); patients were grouped into tertiles of parathyroid hormone levels with the lowest tertile (tertile 1) serving as the reference group.
Mentions: Within the whole study population, the mortality risks for patients in the second or third PTH tertile were not materially different compared to the reference of patients in the lowest PTH tertile (adjusted HRTertile2 1.17, 95% CI 0.95–1.44; adjusted HRTertile3 1.19, 95% CI 0.96–1.47). Investigating the hypothesis of effect modification by wasting, the analyses on PTH and mortality were stratified by wasting as defined by baseline albumin levels. In patients without wasting (albumin >3.8 g/dL, n = 586), the absolute mortality rate during 4 years of follow-up was 15 per 100 person years (py). All-cause mortality increased stepwise with higher PTH levels: it was 11/100 py for patients in the lowest tertile with a PTH ≤46.3 pg/mL, 15/100 py in patients with a PTH between 46.3 and 106 pg/mL (second tertile) and 17/100 py in patients with a PTH >106 pg/mL (third tertile) (Figure 1B and Table 2). In unadjusted Cox regression analyses using PTH as a continuous variable, the relative risk of death increased significantly by 17% per unit increase in log-transformed PTH (HR 1.17, 95% CI 1.04–1.31). The association was even stronger in multivariate analyses with a 23% increase in mortality per unit increase in log-transformed PTH (HR 1.23, 95% CI 1.09–1.39). With multivariate Cox regression models using PTH as a categorical variable, patients in the second PTH tertile had a 37% higher risk of death compared to those in the lowest tertile. Patients with highest PTH levels (third tertile) had the highest mortality, being significantly increased by 74% as compared to patients in the lowest PTH tertile (Table 2). Similar results were found in additional analyses using a BMI >23 kg/m2 to define the absence of wasting. All-cause mortality significantly rose by 15% per unit increase in log-transformed PTH in patients without wasting. In contrast, in patients with the disease state expectedly showing a high incidence of death (the absolute mortality rate was 21/100 py), no association of PTH with mortality was found: death rates were similar across the tertiles of PTH, both in the analyses using albumin and BMI for the definition of wasting.

Bottom Line: Patients had a mean age of 66 +/- 8 years, and 54% were male.Patients in the highest PTH tertile had a 74% higher risk of death (HR(adj) 1.74, 95% CI 1.27-2.40) and a 49% higher risk of CVE (HR(adj) 1.49, 95% CI 1.05-2.11) compared to patients in the lowest PTH tertile.In contrast, no effect was found in patients with wasting.

View Article: PubMed Central - PubMed

Affiliation: Division of Nephrology, Department of Medicine, University of Würzburg, Germany. drechsler_c@medizin.uni-wuerzburg.de

ABSTRACT

Background: The association between parathyroid hormone (PTH) level and mortality in dialysis patients is controversial. We hypothesized that wasting, a common condition potentially related to adynamic bone disease, modifies the association of PTH with mortality and cardiovascular events (CVE), respectively.

Methods: We analysed data from 1255 diabetic haemodialysis patients, participating in the German Diabetes and Dialysis Study between 1998 and 2004. The patients were stratified by the presence or absence of wasting (albumin 3.8 g/dL; BMI 23 kg/m(2)). Using Cox regression analyses, we calculated the risks of (1) all-cause mortality and (2) CVE according to baseline PTH levels. All analyses were adjusted for age, sex, atorvastatin treatment, duration of dialysis, comorbidity, HbA1c, phosphate, calcium, blood pressure, haemoglobin and C-reactive protein.

Results: Patients had a mean age of 66 +/- 8 years, and 54% were male. Among patients without wasting (albumin >3.8 g/dL, n = 586), the risks of death and CVE during 4 years of follow-up significantly increased by 23% and 20% per unit increase in logPTH. Patients in the highest PTH tertile had a 74% higher risk of death (HR(adj) 1.74, 95% CI 1.27-2.40) and a 49% higher risk of CVE (HR(adj) 1.49, 95% CI 1.05-2.11) compared to patients in the lowest PTH tertile. In contrast, no effect was found in patients with wasting. Accordingly, additional analyses in strata of BMI showed that PTH significantly impacted on death and CVE [HR(logPTH)(adj) 1.15 and 1.14, respectively] only in patients without, but not in patients with, wasting.

Conclusions: Wasting modifies the association of PTH with adverse outcomes in diabetic dialysis patients. High PTH levels are of concern in the patients without wasting, while the effect of PTH on mortality is ified in the patients with wasting.

Show MeSH
Related in: MedlinePlus