Low parathyroid hormone status induced by high dialysate calcium is an independent risk factor for cardiovascular death in hemodialysis patients

Abstract

Here we studied a possible association between low parathyroid hormone (PTH) status and mortality in incident patients undergoing hemodialysis . A total of 1983 patients were included at baseline and prospectively followed for 24 months. Patients were classified according to their Kidney Disease: Improving Global Outcomes PTH status at baseline and at 12 months, and mortality evaluated at 12 to 24 months using adjusted Cox analysis. Factors potentially involved in PTH status variability between baseline and 12 months were analyzed. A decrease in serum PTH from normal or high to low values between baseline and 12 months was associated with significantly increased cardiovascular mortality at 12 to 24 months (hazard ratio, 2.03; 95% confidence interval, 1.22-3.36). For patients with high or normal baseline PTH levels, the main independent factor at 6 months for a decrease to low PTH levels at 12 months was high dialysate calcium (1.75 mmol/L), whereas prescription of non-calcium-based phosphate binders was associated with a lower risk of PTH decrease. In the high cardiovascular (CV) mortality risk subgroup of patients who acquired a low PTH status at 12 months, the main independent factor at 12 months associated with significant 12- to 24-month CV mortality was high dialysate calcium (odds ratio, 5.44; 95% CI, 2.52-11.75). Thus, patients with a serum PTH decrease to low values after 1 year of hemodialysis treatment are at high risk of short-term CV death. High dialysate calcium was an important contributor to PTH oversuppression, and continued use was associated with increased CV mortality.

A decrease in intact parathyroid hormone (iPTH) levels is associated with higher mortality in prevalent hemodialysis patients

“…A decrease from baseline high-normal iPTH levels to low levels (heterogeneous definition: <2x lower than the upper limit of normal of the iPTH assay at each center) during the first year of hemodialysis in incident patients, was an independent and strong risk factor for cardiovascular death in the following year, but not for all-cause death, (20). However, the main contributor to the observed decrease in serum iPTH was the use of a high-calcium dialysate concentration (1.75 mmol/L) which was also independently associated with higher mortality risk [18]. By contrast, patients with low baseline iPTH levels that remained within the low iPTH range at month 12 had no increase in cardiovascular death risk and it was not studied whether a decrease in iPTH remaining within the normal-high range was associated with mortality.…”

“…The mechanisms underlying the relationship between ΔiPTH and mortality requires further investigation, as it has the potential to modify daily clinical practice. Possible explanations include the use of therapies that lower iPTH, especially those that have been reported to associate with a negative influence on survival, as may be the case for high dialysate calcium [18]or the presence of nutrition abnormalities such as malnutrition or obesity. However, no data supported these associations in our population, although the number of patients was too low to obtain meaningful information in this regard.…”

Osteoprotegerin Is the Strongest Predictor for Progression of Arterial Calcification in Peritoneal Dialysis Patients

“…The low frequency of high levels of iPTH is also noteworthy; this was probably a result of the high percentage of patients with diabetes in whom iPTH is usually lower than in non-diabetics, and high calcium loads supply by PD and phosphate binders [37]. …”

Analysis of the kinetics of the parathyroid hormone, and of associated patient outcomes, in a cohort of haemodialysis patients

“…Recently, two observational studies have reported an increased rate of mortality associated with low PTH levels [ 15 , 16 ]. However, as these two studies failed to identify the underlying cause of low PTH levels, we believe that their suggestion of a possible risk in treating SHPT in HD patients might be misleading.…”