Mortality risks increase for hemodialysis (HD) patients with abnormal serum phosphorus levels or poor nutritional status, a new study confirms. Furthermore, nutritional status appears to influence the relationship of phosphorus with mortality.

Shingo Fukuma, MD, PhD, of Kyoto University in Kyoto, Japan, and colleagues examined the interaction between time-averaged serum phosphorus concentration and all-cause mortality according to tertiles of the geriatric nutritional risk index (GNRI), an equation incorporating gender, serum albumin, weight, and height.

Of 6230 Japanese HD patients from the Dialysis Outcomes and Practice Pattern Study 1997–2010, 561 died during follow-up (4.6 deaths per 100 person-years). Among patients with low to middle GNRI, those with low (less than 3.5 mg/dL), middle (at least 3.5 but less than 6 mg/dL), and high time-averaged phosphorus levels (6 mg/dL and above) had an approximately 4.3-, 2.1, and 2.2-fold increased risk of all-cause mortality, respectively. Among patients with high GNRI, those with high phosphorus had a 1.7-fold increased risk of all-cause mortality.

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In a time-dependent Cox model, the relative excess risk due to interaction between high phosphorus concentrations and low-middle GNRI was −0.57, “indicating an antagonistic interaction,” the investigators reported. A significant statistical multiplicative interaction between serum phosphorus and GNRI further corroborated the importance of nutritional status.

As for possible reasons for the interaction between phosphorus concentration and GNRI, the researchers observed that “the influence of low-middle GNRI may outweigh the association between high phosphorus concentration and mortality if the association between low-middle GNRI and mortality is stronger than that of high phosphorus concentration and mortality.” 

Another possibility is that the mechanism of the association between phosphorus concentration and mortality may differ by GNRI category. Among patients with a high GNRI, high phosphorus levels could be a risk factor for vascular calcification.

“These results suggest that the association between phosphorus concentration and mortality is indeed modified by nutritional index, suggesting that nutritional index should be considered in the management of phosphorus concentration in haemodialysis patients,” Dr Fukuma and his team wrote in BMJ Open.

In their models, the team adjusted for age, gender, time on dialysis, single-pool Kt/V, comorbid conditions, and use of phosphate binders and vitamin D receptor activators (but not type or dose).

Study limitations include the possibility of residual confounding due to unmeasured factors, which may affect the association between exposure categories and mortality. In addition, the researchers noted that they lacked data from other nutritional scoring tools, such as subjective global assessment and malnutrition-inflammation score, and lacked data on the type and dose of phosphate binders, which could confound the association between phosphorus level and mortality.

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Fukuma S, Ikenoue T, Akizawa T, and Fukuhara S. Impact of nutritional index on the association between phosphorus concentrations and mortality in haemodialysis patients: a cohort study from dialysis outcomes and practice pattern study in Japan. BMJ Open. 2017 Aug 7;7(8):e016682. doi: 10.1136/bmjopen-2017-016682.