Original Investigation
Pathogenesis and Treatment of Kidney Disease
Serum Phosphorus and Progression of CKD and Mortality: A Meta-analysis of Cohort Studies

https://doi.org/10.1053/j.ajkd.2015.01.009Get rights and content

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.

Section snippets

Search Strategy and Selection Criteria

We undertook a systematic review of the literature according to the Meta-analysis of Observational Studies in Epidemiology (MOOSE) reporting guidelines.9 Relevant studies were identified by searching the following data sources: MEDLINE (Ovid; from January 1950 to June 2014), EMBASE (from January 1970 to June 2014), and the Cochrane Library database (Cochrane Central Register of Controlled Trials [CENTRAL]; no date restriction). We used Medical Subject Headings (MeSH) and text words of chronic

Characteristics and Quality of Studies

Our literature search returned 5,891 results for relevant articles. Of these, we reviewed the full text of 55 reports, from which we identified 12 cohort studies of adults with CKD in the meta-analysis (Fig 1). All cohort studies were published from 2005 to 2014 and involved a total of 25,546 patients with CKD.7, 8, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24 Characteristics of included studies are provided in Table 1. Of those patients, 0.6% were in CKD stage 1; 2%, stage 2; 85%, stage 3; and

Discussion

Recent studies have indicated that phosphorus may play an independent pathogenic role in CKD progression,7 but some of those studies are underpowered and yield inconsistent results.8 To our knowledge, this is the first systematic review and meta-analysis of serum phosphorus level and outcomes in CKD and included 12 cohort studies with 25,546 patients with CKD. Our study indicates that higher serum phosphorus level is an independent risk factor for kidney disease progression and mortality among

Acknowledgements

We thank Rajnish Mehrotra and the KEEP Study group, Biagio R. Di Iorio, and Antonio Bellasi for providing useful additional information for this meta-analysis.

Support: Design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript were supported by the Research Special Fund for Public Welfare Industry of Health from National Health and Family Planning Commission of the People’s Republic of China (201002010

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