J Diabetes Complications. 2013 Jul-Aug;27(4):328-32.

Phosphorus as an early marker of morbidity and mortality in type 2 chronic kidney disease diabetic patients.

Ana Paula Silva, André Fragoso, Ana Pinho, Nelson Tavares, Ana Camacho, Marília Faísca, Pedro Leão Neves .

Department  of  Nephrology, Hospital Faro, Faro, Portugal



Aims: To evaluate the association of different phosphorus levels with cardiovascular mortality and hospitalizations risk in type-2 diabetic patients in phase 3/4 of CKD.

Methods: An observational, prospective study involving 119 patients divided into groups according to baseline phosphorus levels: 1 ≤ 3.60 mg/dL; 2, 3.60–4.60 mg/dL; and 3,≥4.60 mg/dL. Baseline characteristics were analyzed and compared. Multivariate Cox regression and Multivariate Logistic regression were used to find out the predictors of cardiovascular mortality and hospitalizations, respectively. T-test was used to investigate the association of phosphorus and start of hemodialysis.

Results: Patients of group 3 presented lower clearance and Hb and increased PTH, Ca×P, LVMI, HOMA, uric acid, IL-6 and more hospitalization days. Patients’ mean survival on groups 1, 2 and 3 was 62.5 ± 1.95, 60.1 ± 2.85 and 52.6 ± 2.84 months, respectively (p = 0.001). Phosphorus and creatinine levels were independent predictors of mortality, and phosphorus, creatinine, PTH and age were independent predictors of hospitalizations in this population. Patients who entered hemodialysis presented greater phosphorus levels than those who did not (5.04 ± 1.31 vs. 4.14 ± 1.09; p = 0.001).

Conclusions: Phosphorus was a predictor of cardiovascular mortality and hospitalizations. Phosphorus levels might have a significant clinical use, possibly translated as an early marker of mortality and hospitalizations in this population.

PMID: 23528898



Hyperphosphatemia is considered to play a crucial role in promoting the co-morbid conditions associated with CKD (Gupta et al., 2011). Epidemiological studies have shown that hyperphosphatemia is associated with unexpectedly high rates of cardiovascular events and death (Locatelli et al., 2003).

Several mechanisms have been proposed to explain how hyperphosphatemia aggravates CVD, including vascular calcification (Alfrey2004; Moe and Chen 2008), associated with concurrent deterioration of the cardiovascular system and, increased parathyroid hormone (PTH) levels (Slatopolsky 2003). This situation is pro-inflammatory and has been reported to produce interleukin 6 (IL-6) which, in turn, is associated with increased CVD risk.

This is a particularly critical health burden in patients with diabetes, who have a risk for clinical CVD two to four times higher than a non-diabetic person (Laakso et al., 1995). In the presence of further aggravated renal disease (diabetic nephropathy), hyperphosphatemia might act as one of the cardiovascular disease markers, by worsening diabetes and related complications (Mahmud et al., 2011).

Based on current available evidences, and encouraged by the scarcity of studies conducted to assess the impact of phosphorus in stages 3 and 4 of renal disease, as well as by the lack of national data, it is important to further investigate the association between phosphorus and cardiovascular mortality and need for hospitalization, in order to clarify the role of phosphorus as a possible early marker of cardiovascular risk in patients with CKD and to try to improve the management of the disease in these patients.

We then hypothesized “Is phosphorus a risk factor for cardiovascular mortality and morbidity in type 2 diabetic subjects with mild to moderate kidney disease (stage 3 and 4)”?

In our study the patients with low phosphorus levels tended to have better survival rates than patients with higher levels of phosphorus

Ana Paula Silva-1

Phosphorus was found to independently predict patient survival, with increased risk of mortality associated with higher phosphorus levels (Fig2).

Ana Paula Silva-2

Phosphorus was found to be a predictive variable of the need for cardiovascular hospitalizations, with increased risk associated with higher serum phosphorus levels (Fig3).

Ana Paula Silva-3

The importance of this study – is supported as it demonstrates that phosphorus levels might have a significant clinical use, possibly being translated as an early marker/predictor of cardiovascular mortality and need for hospitalizations in this population.

In addition, these results assume particular relevance if we take into consideration the relatively early stages of kidney disease presented. It is already well established that hyperphosphatemia is associated with greater cardiovascular mortality and morbidity in patients with end-stage renal disease.



  1. Gupta, D., Brietzke, S., et al. (2011). Phosphate Metabolism in Cardiorenal Metabolic Disease. Cardiorenal Medicine, 1(4), 261–270.
  2. Locatelli, F., Pozzoni, P., et al. (2003). Epidemiology of cardiovascular risk in patients with chronic kidney disease. Nephrology, Dialysis, Transplantation, 18(Suppl 7), vii2–vii9.
  3. Alfrey, A. C. (2004). The role of abnormal phosphorus metabolism in the progression of chronic kidney disease and metastatic calcification. Kidney International, 66(Supplement 90), S13–S17.
  4. Slatopolsky, E. (2003). New developments in hyperphosphatemia management. Journal of the American Society of Nephrology, 14, S297–S299.
  5. Laakso, M., Rönnemaa, T., et al. (1995). Does NIDDM increase the risk for coronary heart disease similarly in both low- and high-risk populations? Diabetologia, 38(4), 487–493.
  6. Mahmud, I., Rahman, Z., et al. (2011). Hyperphosphataemia Is Associated with the Diabetes-related Cardiovascular Risk Factors. Journal of Oleo Science, 60(2), 79–85.


Ana Paula Silva-4


Ana Paula Silva


Department  of  Nephrology, Hospital Faro, Portugal

Rua Leão Penedo 8000-386



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