Disorders in bone-mineral parameters and the risk of death in persons with chronic kidney disease stages 4 and 5: the PECERA study.

Abstract

Abnormalities of bone mineral parameters are associated with increased mortality in patients on dialysis, but their effects and the optimal range of these biomarkers are less well characterized in non-dialysis chronic kidney disease (CKD). PECERA (Collaborative Study Project in Patients with Advanced CKD) is a 3-year, prospective multicenter, open-cohort study of 966 adult patients with non-dialyzed CKD stages 4-5 enrolled from 12 centers in Spain. Associations between levels of serum calcium (Ca) (corrected for albumin), phosphate (P), and intact parathyroid hormone (iPTH) with all-cause mortality (primary outcome) and cardiovascular mortality (secondary outcome) were examined using time-dependent Cox proportional hazards models and penalized splines analysis adjusted by demographics and comorbidities, treatments and biochemical values collected every 6months for 3years. After a median follow-up of 29months (IQR: 13-36months) there were 181 deaths (19%). The association of calcium with all-cause mortality was J-shaped, with an increased risk for all-cause mortality at levels > 10.5mg/dL. For phosphate and iPTH levels, the association was U-shaped. The serum values associated with the minimum risk of mortality were 3.8mg/dL for phosphate and 70pg/mL for iPTH, being the lowest risk ranges between 2.8 and 5.0mg/dL, and between 38 and 112pg/mL for phosphate and iPTH, respectively. Our study provides evidence on the non-linear association of serum calcium, phosphate and iPTH levels with mortality in stage 4 and 5 CKD patients, and suggests potential survival benefits for controlling bone mineral parameters in this population, as previously reported for dialysis patients.