Serum Phosphorus and Progression of CKD and Mortality: A Meta-analysis of Cohort Studies

Background Recent studies have indicated that phosphorus may play an independent pathogenic role in chronic kidney disease (CKD) progression, but some of those studies were underpowered and yielded inconsistent results. Study Design Systematic review and meta-analysis. Setting & Population Non–dialysis-dependent patients with CKD (transplant recipients were excluded). Selection Criteria for Studies Studies assessing the risk ratio of serum phosphorus level on kidney failure and mortality for non–dialysis-dependent patients with CKD published from January 1950 to June 2014 were included following systematic searching of MEDLINE, EMBASE, and the Cochrane Library. Predictor Serum phosphorus level. Outcome Kidney failure, defined as doubled serum creatinine level, 50% decline in estimated glomerular filtration rate, or end-stage kidney disease. Results In 12 cohort studies with 25,546 patients, 1,442 (8.8%) developed kidney failure and 3,089 (13.6%) died. Overall, every 1-mg/dL increase in serum phosphorus level was associated independently with increased risk of kidney failure (hazard ratio, 1.36; 95% CI, 1.20-1.55) and mortality (hazard ratio, 1.20; 95% CI, 1.05-1.37). Limitations Existence of potential residual confounding could not be excluded. Conclusions This meta-analysis suggests an independent association between serum phosphorus level and kidney failure and mortality among non–dialysis-dependent patients with CKD and suggests that large-scale randomized controlled trials should target disordered phosphorus homeostasis in CKD. Recent studies have indicated that phosphorus may play an independent pathogenic role in chronic kidney disease (CKD) progression, but some of those studies were underpowered and yielded inconsistent results. Systematic review and meta-analysis. Non–dialysis-dependent patients with CKD (transplant recipients were excluded). Studies assessing the risk ratio of serum phosphorus level on kidney failure and mortality for non–dialysis-dependent patients with CKD published from January 1950 to June 2014 were included following systematic searching of MEDLINE, EMBASE, and the Cochrane Library. Serum phosphorus level. Kidney failure, defined as doubled serum creatinine level, 50% decline in estimated glomerular filtration rate, or end-stage kidney disease. In 12 cohort studies with 25,546 patients, 1,442 (8.8%) developed kidney failure and 3,089 (13.6%) died. Overall, every 1-mg/dL increase in serum phosphorus level was associated independently with increased risk of kidney failure (hazard ratio, 1.36; 95% CI, 1.20-1.55) and mortality (hazard ratio, 1.20; 95% CI, 1.05-1.37). Existence of potential residual confounding could not be excluded. This meta-analysis suggests an independent association between serum phosphorus level and kidney failure and mortality among non–dialysis-dependent patients with CKD and suggests that large-scale randomized controlled trials should target disordered phosphorus homeostasis in CKD.