Changes in 3-month mineral and bone disorder patterns were associated with all-cause mortality in prevalent hemodialysis patients with secondary hyperparathyroidism

Abstract

Background: There is limited evidence on the association between short-term changes in mineral and bone disorder parameters and survival in maintenance hemodialysis patients.

Methods: We investigated the association between changing patterns of phosphorus, calcium and intact parathyroid hormone levels and all-cause mortality in hemodialysis patients with secondary hyperparathyroidism. Each parameter was divided into three categories (low [L], middle [M] and high [H]), and the changing patterns between two consecutive visits at 3-month intervals were categorized into nine groups (e.g., L-L and M-H). The middle category was defined as 4.0-7.0 mg/dL for phosphorous, 8.5-9.5 mg/dL for calcium and 200-500 pg/mL for intact parathyroid hormone. Adjusted incidence rates and rate ratios were analyzed by weighted Poisson regression models accounting for time-dependent exposures.

Results: For phosphorus, shifts from low/high to middle category (L-M/H-M) were associated with a lower mortality compared with the L-L and H-H groups, whereas shifts from middle to low/high category (M-L/M-H) were associated with a higher mortality compared with the M-M group. For calcium, shifts from low/middle to high category (L-H/M-H) were associated with a higher mortality compared with the L-L and M-M groups, whereas shifts from high to middle category (H-M) were associated with a lower mortality compared with the H-H group. For intact parathyroid hormone, shifts from low to middle category (L-M) were associated with a lower mortality compared with the L-L group.

Conclusions: Changes in the 3-month patterns of phosphorus and calcium toward the middle category were associated with lower mortality. Our study also suggests the importance of avoiding hypercalcemia.

Trial registration: ClinicalTrials.gov NCT00995163.

Keywords: CKD-MBD; Changing pattern; Hemodialysis; Mortality; Secondary hyperparathyroidism.

Conflict of interest statement

CK, SA, TN and MW are employees of Kyowa Kirin Co. ltd., (KKC). NF received grants from KKC. CM and YO do not have any conflicts of interest to declare. SF1 has acted as a scientific advisor for KKC. SF2 has acted as a scientific advisor for and has received grants from KKC. MF has received consulting fees from KKC and Ono Pharmaceutical; lecture fees from KKC, Bayer, Torii Pharmaceutical and Ono Pharmaceutical; and grants from KKC, Bayer and Ono Pharmaceutical. TA has received personal fees from KKC, Astellas Pharma, Bayer, Fuso Pharmaceutical, Japan Tobacco, Ono Pharmaceutical, NIPRO, Chugai Pharmaceutical, Kissei Pharmaceutical, Torii Pharmaceutical and Otsuka Pharmaceutical.

Figures

Fig. 1

Study design of the MBD-5D study.The study has a whole cohort (solid circle) of all patients enrolled and a subcohort (dotted circle) of randomly selected 40% of the whole cohort. From 86 facilities, all 8,229 dialysis patients with secondary hyperparathyroidism were registered and 3,276 patients were selected into the subcohort. In total, 1,226 all-cause deaths and 462 deaths due to cardiovascular disease were reported. CV, cardiovascular

Fig. 2

Illustration of changing patterns of MBD parameters and outcome. Levels of each parameter were divided into three categories (Low, Middle and High); the middle categories were defined as 4.0–7.0 mg/dL for phosphorus, 8.5–9.5 mg/dL for calcium and 200–500 pg/mL for intact parathyroid hormone. MBD, mineral and bone disorder

Fig. 3

aIRRs for each combination of the values at baseline and 3 months later. Levels of each parameter were divided into three categories (L, M and H); the middle category were defined as 4.0–7.0 mg/dL for phosphorus, 8.5–9.5 mg/dL for calcium and 200–500 pg/mL for intact PTH. For each 3-month interval ending at visit t, the changing patterns of MBD parameters during the previous 3-month interval from visit t—2 (baseline) to visit t—1 (3 months later) were evaluated. Incidence rate ratios were adjusted for patients’ characteristics (age, sex, primary kidney disease, diabetes, dialysis vintage, cardiovascular disease, lung disease, liver disease, malignancy and history of parathyroidectomy) and time-varying variables (VDRAs, phosphate binders, cinacalcet, albumin, hemoglobin, body mass index, Kt/V and dialysate Ca concentration). aIRRs, adjusted incident rate ratios; H, high; PTH, parathyroid hormone; L, low; M, middle; MBD, mineral and bone disorder; ref, reference; VDRA, vitamin D receptor activator

Fig. 4

aIRRs for each combination of the values at baseline and 12 months later. Levels of each parameter were divided into three categories (L, M and H); the middle category were defined as 4.0–7.0 mg/dL for phosphorus, 8.5–9.5 mg/dL for calcium and 200–500 pg/mL for intact PTH. For each 12-month interval ending at visit t, the changing patterns of MBD parameters during the previous 12-month interval from visit t—2 (baseline) to visit t—1 (12 months later) were evaluated. Incidence rate ratios were adjusted for patients’ characteristics (age, sex, primary kidney disease, diabetes, dialysis vintage, cardiovascular disease, lung disease, liver disease, malignancy and history of parathyroidectomy) and time-varying variables (VDRAs, phosphate binders, cinacalcet, albumin, hemoglobin, body mass index, Kt/V and dialysate Ca concentration). aIRRs, adjusted incident rate ratios; H, high; PTH, parathyroid hormone; L, low; M, middle; MBD, mineral and bone disorder; ref, reference; VDRA, vitamin D receptor activator