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Serum iPTH, calcium and phosphate, and the risk of mortality in a European haemodialysis population.

Floege J, Kim J, Ireland E, Chazot C, Drueke T, de Francisco A, Kronenberg F, Marcelli D, Passlick-Deetjen J, Schernthaner G, Fouqueray B, Wheeler DC, ARO Investigato - Nephrol. Dial. Transplant. (2010)

Bottom Line: TD analysis confirmed the results for iPTH.TD analysis confirmed the results for phosphate <1.13 mmol/L.FP analysis confirmed the results of baseline and TD analyses.

View Article: PubMed Central - PubMed

Affiliation: Div. Nephrology, RWTH University of Aachen, Germany. juergen.floege@rwth-aachen.de

ABSTRACT

Background: A number of US observational studies reported an increased mortality risk with higher intact parathyroid hormone (iPTH), calcium and/or phosphate. The existence of such a link in a European haemodialysis population was explored as part of the Analysing Data, Recognising Excellence and Optimising Outcomes (ARO) Chronic Kidney Disease (CKD) Research Initiative.

Methods: The association between the markers of mineral and bone disease and clinical outcomes was examined in 7970 patients treated in European Fresenius Medical Care facilities over a median of 21 months. Baseline and time-dependent (TD) Cox regression were performed using Kidney Disease Outcomes Quality Initiative (KDOQI) target ranges as reference categories, adjusting for demographics, medical history, dialysis parameters, inflammation, medications and laboratory parameters. Fractional polynomial (FP) models were also used.

Results: Hazard ratio (HR) estimates from baseline analysis for iPTH were U-shaped [>600 pg/mL, HR = 2.10, 95% confidence interval (CI) 1.62-2.73; <75 pg/mL, HR = 1.46, 95% CI 1.17-1.83]. TD analysis confirmed the results for iPTH. Baseline analysis showed that calcium >2.75 mmol/L increased risk of death (HR = 1.70, 95% CI 1.19-2.42). TD analysis showed that both low (HR = 1.19, 95% CI 1.04-1.37) and high calcium (HR = 1.74, 95% CI 1.30-2.34) increased risk of death. Baseline analysis for phosphate showed a U-shaped pattern (<1.13 mmol/L, HR = 1.18, 95% CI 1.01-1.37; >1.78 mmol/L, HR = 1.32, 95% CI 1.13-1.55). TD analysis confirmed the results for phosphate <1.13 mmol/L. HR estimates were higher in patients with diabetes versus those without diabetes for baseline analysis only (P-value = 0.014). FP analysis confirmed the results of baseline and TD analyses.

Conclusion: Patients with iPTH, calcium and phosphate levels within the KDOQI target ranges have the lowest risk of mortality compared with those outside the target ranges.

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Related in: MedlinePlus

Relative risk of all-cause mortality for iPTH baseline Cox regression using fractional polynomials in patients with diabetes and without diabetes. Values <0.5% percentile and >99.5% percentile were removed from both models (no history of diabetes model = 22 observations removed; history of diabetes model = 7 observations removed). Number of observations used: no history of diabetes model = 2906; history of diabetes model = 1011. iPTH values >1000 pg/mL not shown. No history of diabetes: log (HR) = −0.23 log iPTH + 0.001iPTH1 + βk×k (P = 0.03); history of diabetes model: log (HR) = −0.70 log iPTH + 0.11 iPTH0.5 + βk×k (P = 0.03). Adjusted for demographics (age, gender, country, body mass index, smoking status), medical history (chronic kidney disease aetiology, history of diabetes, history of CVD and history of cancer), dialysis parameters [dialysis vintage, vascular access type, dialysis adequacy (Kt/V) and blood flow], markers of inflammation (serum albumin and C-reactive protein), CVD medications (antihypertensives, angiotensin-converting enzyme inhibitors, oral anticoagulants and anti-aggregants), mineral and bone disorder medications (oral vitamin D and phosphate binders), calcium, phosphate, haemoglobin, ferritin, cholesterol, blood leucocytes, hospitalization, and change in vascular access type.
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fig2: Relative risk of all-cause mortality for iPTH baseline Cox regression using fractional polynomials in patients with diabetes and without diabetes. Values <0.5% percentile and >99.5% percentile were removed from both models (no history of diabetes model = 22 observations removed; history of diabetes model = 7 observations removed). Number of observations used: no history of diabetes model = 2906; history of diabetes model = 1011. iPTH values >1000 pg/mL not shown. No history of diabetes: log (HR) = −0.23 log iPTH + 0.001iPTH1 + βk×k (P = 0.03); history of diabetes model: log (HR) = −0.70 log iPTH + 0.11 iPTH0.5 + βk×k (P = 0.03). Adjusted for demographics (age, gender, country, body mass index, smoking status), medical history (chronic kidney disease aetiology, history of diabetes, history of CVD and history of cancer), dialysis parameters [dialysis vintage, vascular access type, dialysis adequacy (Kt/V) and blood flow], markers of inflammation (serum albumin and C-reactive protein), CVD medications (antihypertensives, angiotensin-converting enzyme inhibitors, oral anticoagulants and anti-aggregants), mineral and bone disorder medications (oral vitamin D and phosphate binders), calcium, phosphate, haemoglobin, ferritin, cholesterol, blood leucocytes, hospitalization, and change in vascular access type.

Mentions: We found evidence of an interaction between history of diabetes, iPTH and mortality in the baseline Cox model, in which the relative risk estimates were higher among patients with diabetes than those without diabetes (P = 0.014). Patients with diabetes in the highest iPTH category had nearly a 3-fold increase in risk of death compared to patients who were within the target range (HR 2.89, 95% CI 1.73–4.82, P < 0.001). Conversely, for patients without diabetes, the increase in risk of death was <2-fold (HR 1.85, 95% CI 1.36–2.52, P < 0.001). Moreover, patients with diabetes in the lowest iPTH category had almost a 2-fold increase in the risk of mortality (HR 1.89, 95% CI 1.27–2.81, P = 0.002) than patients without diabetes, whose relative risk estimates were attenuated (HR 1.29, 95% CI 0.98–1.70, P = 0.070). In contrast to the baseline analysis, the test for interaction between diabetes, iPTH and mortality in the time-dependent analysis was not statistically significant (P = 0.233). Results of the Cox regression models based on FP analysis confirmed the overall trends in the relative risk estimates for iPTH (Figures 1a and 2). The FP analysis also showed an attenuation of effect in the time-dependent analysis with higher values of iPTH.


Serum iPTH, calcium and phosphate, and the risk of mortality in a European haemodialysis population.

Floege J, Kim J, Ireland E, Chazot C, Drueke T, de Francisco A, Kronenberg F, Marcelli D, Passlick-Deetjen J, Schernthaner G, Fouqueray B, Wheeler DC, ARO Investigato - Nephrol. Dial. Transplant. (2010)

Relative risk of all-cause mortality for iPTH baseline Cox regression using fractional polynomials in patients with diabetes and without diabetes. Values <0.5% percentile and >99.5% percentile were removed from both models (no history of diabetes model = 22 observations removed; history of diabetes model = 7 observations removed). Number of observations used: no history of diabetes model = 2906; history of diabetes model = 1011. iPTH values >1000 pg/mL not shown. No history of diabetes: log (HR) = −0.23 log iPTH + 0.001iPTH1 + βk×k (P = 0.03); history of diabetes model: log (HR) = −0.70 log iPTH + 0.11 iPTH0.5 + βk×k (P = 0.03). Adjusted for demographics (age, gender, country, body mass index, smoking status), medical history (chronic kidney disease aetiology, history of diabetes, history of CVD and history of cancer), dialysis parameters [dialysis vintage, vascular access type, dialysis adequacy (Kt/V) and blood flow], markers of inflammation (serum albumin and C-reactive protein), CVD medications (antihypertensives, angiotensin-converting enzyme inhibitors, oral anticoagulants and anti-aggregants), mineral and bone disorder medications (oral vitamin D and phosphate binders), calcium, phosphate, haemoglobin, ferritin, cholesterol, blood leucocytes, hospitalization, and change in vascular access type.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3107766&req=5

fig2: Relative risk of all-cause mortality for iPTH baseline Cox regression using fractional polynomials in patients with diabetes and without diabetes. Values <0.5% percentile and >99.5% percentile were removed from both models (no history of diabetes model = 22 observations removed; history of diabetes model = 7 observations removed). Number of observations used: no history of diabetes model = 2906; history of diabetes model = 1011. iPTH values >1000 pg/mL not shown. No history of diabetes: log (HR) = −0.23 log iPTH + 0.001iPTH1 + βk×k (P = 0.03); history of diabetes model: log (HR) = −0.70 log iPTH + 0.11 iPTH0.5 + βk×k (P = 0.03). Adjusted for demographics (age, gender, country, body mass index, smoking status), medical history (chronic kidney disease aetiology, history of diabetes, history of CVD and history of cancer), dialysis parameters [dialysis vintage, vascular access type, dialysis adequacy (Kt/V) and blood flow], markers of inflammation (serum albumin and C-reactive protein), CVD medications (antihypertensives, angiotensin-converting enzyme inhibitors, oral anticoagulants and anti-aggregants), mineral and bone disorder medications (oral vitamin D and phosphate binders), calcium, phosphate, haemoglobin, ferritin, cholesterol, blood leucocytes, hospitalization, and change in vascular access type.
Mentions: We found evidence of an interaction between history of diabetes, iPTH and mortality in the baseline Cox model, in which the relative risk estimates were higher among patients with diabetes than those without diabetes (P = 0.014). Patients with diabetes in the highest iPTH category had nearly a 3-fold increase in risk of death compared to patients who were within the target range (HR 2.89, 95% CI 1.73–4.82, P < 0.001). Conversely, for patients without diabetes, the increase in risk of death was <2-fold (HR 1.85, 95% CI 1.36–2.52, P < 0.001). Moreover, patients with diabetes in the lowest iPTH category had almost a 2-fold increase in the risk of mortality (HR 1.89, 95% CI 1.27–2.81, P = 0.002) than patients without diabetes, whose relative risk estimates were attenuated (HR 1.29, 95% CI 0.98–1.70, P = 0.070). In contrast to the baseline analysis, the test for interaction between diabetes, iPTH and mortality in the time-dependent analysis was not statistically significant (P = 0.233). Results of the Cox regression models based on FP analysis confirmed the overall trends in the relative risk estimates for iPTH (Figures 1a and 2). The FP analysis also showed an attenuation of effect in the time-dependent analysis with higher values of iPTH.

Bottom Line: TD analysis confirmed the results for iPTH.TD analysis confirmed the results for phosphate <1.13 mmol/L.FP analysis confirmed the results of baseline and TD analyses.

View Article: PubMed Central - PubMed

Affiliation: Div. Nephrology, RWTH University of Aachen, Germany. juergen.floege@rwth-aachen.de

ABSTRACT

Background: A number of US observational studies reported an increased mortality risk with higher intact parathyroid hormone (iPTH), calcium and/or phosphate. The existence of such a link in a European haemodialysis population was explored as part of the Analysing Data, Recognising Excellence and Optimising Outcomes (ARO) Chronic Kidney Disease (CKD) Research Initiative.

Methods: The association between the markers of mineral and bone disease and clinical outcomes was examined in 7970 patients treated in European Fresenius Medical Care facilities over a median of 21 months. Baseline and time-dependent (TD) Cox regression were performed using Kidney Disease Outcomes Quality Initiative (KDOQI) target ranges as reference categories, adjusting for demographics, medical history, dialysis parameters, inflammation, medications and laboratory parameters. Fractional polynomial (FP) models were also used.

Results: Hazard ratio (HR) estimates from baseline analysis for iPTH were U-shaped [>600 pg/mL, HR = 2.10, 95% confidence interval (CI) 1.62-2.73; <75 pg/mL, HR = 1.46, 95% CI 1.17-1.83]. TD analysis confirmed the results for iPTH. Baseline analysis showed that calcium >2.75 mmol/L increased risk of death (HR = 1.70, 95% CI 1.19-2.42). TD analysis showed that both low (HR = 1.19, 95% CI 1.04-1.37) and high calcium (HR = 1.74, 95% CI 1.30-2.34) increased risk of death. Baseline analysis for phosphate showed a U-shaped pattern (<1.13 mmol/L, HR = 1.18, 95% CI 1.01-1.37; >1.78 mmol/L, HR = 1.32, 95% CI 1.13-1.55). TD analysis confirmed the results for phosphate <1.13 mmol/L. HR estimates were higher in patients with diabetes versus those without diabetes for baseline analysis only (P-value = 0.014). FP analysis confirmed the results of baseline and TD analyses.

Conclusion: Patients with iPTH, calcium and phosphate levels within the KDOQI target ranges have the lowest risk of mortality compared with those outside the target ranges.

Show MeSH
Related in: MedlinePlus