Investigators have identified clinical ranges of chronic kidney disease-mineral bone disorder parameters (CKD-MBD) associated with the lowest mortality risks among patients with nondialysis-dependent chronic kidney disease (NDD-CKD).
In a study of 966 patients with CKD stage 4 or 5 not receiving dialysis, the serum values associated with the least risk for all-cause mortality were 3.8 mg/dL for phosphate, 70 pg/mL for iPTH, and 9.5 mg/dL for calcium, Pablo Molina, MD, PhD, of Hospital Universitari Dr Peset, in Valencia, Spain, and colleagues reported in the Journal of Nephrology. These specific values fell within the lowest risk ranges of 2.8-5.0 mg/dL for phosphate, 38-112 pg/mL for iPTH, and 10.5 mg/dL or less for calcium.
The phosphate and calcium ranges corroborate Kidney Disease Improving Global Outcomes (KDIGO) guidelines recommending more normal phosphate and avoidance of hypocalcemia. The iPTH finding, however, is novel, with the observed iPTH thresholds lower than currently recommended, according to the investigators
“In the absence of trial evidence, our results may inform clinical decisions on when to initiate or intensify therapeutic strategies to control CKD-MBD disorders in advanced CKD,” according to Dr Molina’s team.
The study patients were part of PECERA (Collaborative Study Project In Patients with Advanced Renal Failure), the largest and longest prospective, observational cohort of patients with stages 4 to 5 NDD-CKD, according to the study authors. Over a median 29 months, 181 patients (19%) died.
Both low and high phosphate and iPTH levels were associated with increased risk for mortality in a U-shaped curve. Only high calcium was associated with greater death risk in a J-shaped curve.
High calcium levels have been linked to vascular calcification, adynamic bone disease and immobility, the investigators noted. Abnormal levels of iPTH correlate with left ventricular myocardial function, cardiac fibrosis, vascular calcification, and bone remodeling. Phosphate possibly increases fibroblast growth factor-23, vascular calcification, atherosclerosis, and myocardial hypertrophy.
Molina P, Molina MD, Pallardó LM, et al. Disorders in bone‑mineral parameters and the risk of death in persons with chronic kidney disease stages 4 and 5: the PECERA study. Published online January 4, 2021. J Nephrol. doi:10.1007/s40620-020-00916-9