Associação do fósforo sérico com mortalidade em uma coorte de pacientes incidentes em hemodiálise derivada do Registro Brasileiro de Diálise.

Abstract

Background. Mineral and bone disorders are frequently present in patients with kidney failure and have been implicated in reduced survival. However, it is still necessary to establish a definitive association between hyperphosphatemia and increased mortality in this population. Objective. To establish frequency of three phosphate-level ranges and evaluate their association with mortality in a cohort of incident hemodialysis (HD) patients. Methods. This is a retrospective cohort study, using the data from the Brazilian Dialysis Registry, which included 6214 incident adult patients on HD for >3 months. Data were collected from Jan/2011 to Dec/2018. Serum phosphate was stratified into 3 ranges: <3.5mg/dl, 3.5mg/dl - 5.5mg/dl, >5.5 mg/dl. The primary endpoint was 4-year all-cause-mortality. Kaplan-Meier method was used for survival analysis and Cox proportional hazard regression was used to estimate the hazard ratio of mortality after adjusting for: age, body mass index (BMI), skin color, type of dialysis funding, prescription of phosphate binders, heart failure, previous kidney transplantation, hemoglobin, ferritin, calcium, PTH, urea reduction rate (URR), and albumin. To better explore our results, we performed some subgroup analyses, dichotomizing the sample according to some pre-established variables. Results. The frequencies of cases in the lower, normal, and upper phosphate ranges were 5.8%, 64.6%, and 29.6%, respectively. The 4-year survival rates in the three cited phosphate ranges were 60.8%, 70.4%, and 73.1%, respectively. In the fully adjusted multivariate analysis, phosphate in the upper showed a strong association with mortality (HR 1.54, 95% CI 1.21-1.95, P < 0.001). Age (HR 1.03, 95% CI 1.02-1.04, P <0.001) and BMI <18.5 kg/m2 (HR 1.92, 95% CI 1.35 - 2.73, P <0.001) also exhibited a direct association with mortality. In contrast, BMI ≥ 25 kg/m2 (HR 0.80, 95% CI 0.65 - 0.99, P = 0.043) and the use of sevelamer alone (HR 0.44, 95% CI 0.32-0.60, P <0.001) or in association with calcium-based phosphate binders (HR 0.63, 95% CI 0.40-0.98, P = 0.041) proved protective. In subgroup analyses, low phosphate was significantly associated with mortality only in patients <60 years. In contrast, high phosphate had a significant association with mortality in the subgroups of: <60 years and ≥ 60 years; BMI < 25 kg/m2; public or private HD funding; with and without sevelamer prescription; as well as in the apparently healthier patients with hemoglobin, albumin, and PRU in the recommended ranges. Conclusion. Considering the serum phosphate values of the entire hemodialysis treatment, the study reinforced the association of high phosphate levels with mortality in incident patients. The use of sevelamer seemed to be associated with a lower mortality rate when compared to the use of calcium-based phosphate binders.