For their meta-analysis, the investigative team led by Jingjing Da, MD, and Xinfang Xie, MD, of Peking University in Beijing, pooled results from 12 cohort studies (2005-2014) involving 25,546 CKD patients not receiving hemodialysis. Of the patients, 0.6% had stage 1 disease, 2% stage 2, 85% stage 3, and 12.4% stages 4 and 5.
Kidney failure developed in nearly 9% of patients, according to results published online ahead of print in the American Journal of Kidney Diseases. The researchers defined kidney failure as a doubling of serum creatinine levels, a 50% decline in estimated glomerular filtration rate, or end-stage renal disease (ESRD). Every 1 mg/dL increase in serum phosphorus level was independently associated with 36% greater risk of kidney failure and 20% greater risk of mortality.
“[The study] highlights the necessity of monitoring biomarkers related to phosphorus homeostasis in patients with an early stage of CKD,” the investigators wrote.
Previous studies have linked higher serum phosphorus levels with cardiovascular events and mortality. This study is among those indicating an association with kidney disease progression.
Several mechanisms could contribute to a possible cause-and-effect relationship, the researchers suggested. Increased phosphate load may lead to tubular injury, interstitial fibrosis, endothelial dysfunction, and vascular calcification (via phosphate or calcium-phosphate crystals). The crystals may deposit in tubular cells, damaging them and leading to progressive kidney loss. Alternatively, communication between high serum phosphorus levels and the disordered system regulating renal excretion of phosphorus may lead to kidney damage.
The investigators said they could not rule out residual confounding due to limitations of the individual studies.