Serum levels of phosphorus, parathyroid hormone, and calcium and risks of death and cardiovascular disease in individuals with chronic kidney disease – a systemic review and meta-analysis

Abstract

lines are a powerful influence on management strategies for common conditions. When evidence that treating risk factors reduces disease and improves health outcomes is provided by large and well-conducted randomized controlled trials, guidelines can appropriately summarize the relevant data and widely disseminate recommendations for best practice. However, when practice guidelines promote therapeutic strategies without sufficient evidence of effectiveness or harms, overtreatment and widespread inappropriate use of medications, services, or devices may occur. Accordingly, guidelines may recommend health interventions that do not actually improve population outcomes or the quality of care, unnecessarily increase health care expenditure , and may even harm individuals who might be expected to receive small or negligible treatment benefit. An important example is anemia in chronic kidney disease. Guidelines 1,2 For editorial comment see p 1138. Context Clinical practice guidelines on the management of mineral and bone disorders due to chronic kidney disease recommend specific treatment target levels for serum phosphorus, parathyroid hormone, and calcium. Objective To assess the quality of evidence for the association between levels of serum phosphorus, parathyroid hormone, and calcium and risks of death, cardiovas-cular mortality, and nonfatal cardiovascular events in individuals with chronic kidney disease. Data Sources The databases of MEDLINE (1948 to December 2010) and EMBASE (1947 to December 2010) were searched without language restriction. Hand searches also were conducted of the reference lists of primary studies, review articles, and clinical guidelines along with full-text review of any citation that appeared relevant. Study Selection Of 8380 citations identified in the original search, 47 cohort studies (N=327 644 patients) met the inclusion criteria. Data Extraction The characteristics of study design, participants, exposures, and covariates together with the outcomes of all-cause mortality, cardiovascular mortality , and nonfatal cardiovascular events at different levels of serum phosphorus, para-thyroid hormone, and calcium were analyzed within studies. Data were summarized across studies (when possible) using random-effects meta-regression. Data Synthesis The risk of death increased 18% for every 1-mg/dL increase in serum phosphorus (relative risk [RR], 1.18 [95% confidence interval {CI}, 1.12-1.25]). There was no significant association between all-cause mortality and serum level of parathy-roid hormone (RR per 100-pg/mL increase, 1.01 [95% CI, 1.00-1.02]) or serum level of calcium (RR per 1-mg/dL increase, 1.08 [95% CI, 1.00-1.16]). Data for the association between serum level of phosphorus, parathyroid hormone, and calcium and cardiovas-cular death were each available in only 1 adequately adjusted cohort study. Lack of adjustment for confounding variables was not a major limitation of the available studies. Conclusions The evidentiary basis for a strong, consistent, and independent association between serum levels of calcium and parathyroid hormone and the risk of death and cardiovascular events in chronic kidney disease is poor. There appears to be an association between higher serum levels of phosphorus and mortality in this population.