Abstract
Patients with chronic kidney disease (CKD) frequently develop mineral and bone disorders and calcific cardiovascular abnormalities. Clinical management guidelines and treatment strategies are aimed at correcting serum concentrations of phosphorus, calcium and parathyroid hormone, due to an association between these analytes and vascular disease and mortality. However, randomized clinical trials have not demonstrated that treating mineral concentration abnormalities with existing treatment options lowers the risk of cardiovascular events or death.
This systemic review and meta-analysis assessed the quality of evidence in CKD patients, for the association between the serum concentrations of phosphorus, parathyroid hormone and calcium and the risks of mortality, cardiovascular mortality, and non-fatal cardiovascular events. MEDLINE, EMBASE and hand-searches yielded 327,644 adult patients from 47 cohort studies that met the inclusion criteria. Data extracted from these studies included characteristics of the study design, participants, exposures, covariates (age, race, time receiving dialysis [or duration of CKD]), cardiovascular disease and diabetes mellitus; together with relative risk (RR) of all-cause mortality, cardiovascular mortality and non-fatal cardiovascular events per 1 mg/dL (0.32 mmol/L) increase in phosphorus concentration, 100 ng/L (10.6 pmol/L) increase in parathyroid hormone (PTH) concentration and 1 mg/dL (0.25 mmol/L) increase in calcium concentration. When possible, the extracted data were summarized across studies using random-effects meta-regression.
The authors found no evidence for an association between all-cause mortality and serum concentrations of either calcium (RR per 0.25 mmol/L increase, 1.08 [95% Cl, 1.00–1.16]) or PTH (RR per 100 ng/L increase, 1.01 [95% Cl, 1.00–1.02]), but did find an association with higher serum concentrations of phosphorus and mortality (RR per 0.32 mmol/L increase, 1.18 [95% Cl, 1.12–1.25]). The results presented within this systematic review and meta-analysis highlight the lack of evidence used to inform clinical decision-making and practice guidelines for targeting serum concentrations of calcium and PTH as risk factors in patients with CKD. However, there does appear to be an association between higher serum concentrations of phosphorus and mortality in the population studied.