Studies have linked it to various factors, including inflammation and hyperparathyroidism.

In dialysis patients, hypoalbuminemia is a strong predictor of poor outcomes. Although low serum albumin is often attributed to inadequate protein intake, there is evidence that inflammation may be the predominant cause. Since albumin is a negative acute-phase reactant, non-nutritional factors like inflammation depress albumin synthesis.

The National Kidney Foundation (NKF) Kidney Disease Outcomes Quality Initiative (KDOQI) clinical practice guidelines for CVD in dialysis patients acknowledge that “in studies in which the effect of inflammation (measured by CRP [C-reactive protein] levels) is also accounted for in multiple regression analysis, low serum albumin levels tend to lose predictive power, suggesting that inflammation may be a more powerful predictor of poor outcome.”

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The guidelines cite two large studies to support this position. Pifer et al (Kidney Int. 2002;62:2238-2245) examined nutritional indicators and risk of death in 7,719 hemodialysis patients, with results indicating that “the risk of mortality increased with higher baseline and six-month increases in neutrophil count,” a marker for infection or inflammation.

Similarly, a study of 25,661 hemodialysis patients by Reddan et al (Nephrol Dial Transplant. 2003;18:1167-1173) found that “increased neutrophil count and reduced lymphocyte count are independent predictors of increased mortality risk” in the dialysis population.

Mechanisms related to inflammation that also impact albumin involve pro-inflammatory cytokines (interleukin-1 [IL-1], IL-6, and tumor necrosis factor-α [TNF-α]), which have been shown to decrease appetite and increase protein catabolism.

A recent study by Akgul et al (Hemodial Int. 2007;11:198-203) found that TNF-α was positively correlated with malnutrition-inflammation score (MIS) in a study group of 88 maintenance hemodialysis patients, even in the presence of relatively low levels of CRP (10 mg/L or less). The authors also note that dosing requirements for recombinant human erythropoietin (rHuEPO) were increased in patients with MIS and suggest that “future research should focus on reversing the undergoing microinflammation for a better outcome in dialysis patients.”

A modifiable source of inflammation in hemodialysis patients relates to choice of vascular access. Chand et al (Nephron Clin Pract. 2008;108:c91-c98) examined data from more than 12,000 hemodialysis patients with respect to access type and outcome measures. The use of central venous catheters (CVCs) was associated with lower serum albumin compared with arteriovenous fistulas or grafts. Because CVCs were also correlated with poorer adequacy of dialysis (Kt/V), the authors propose that this “contributes to an increased inflammatory state and anorexia, leading to the lower albumin levels observed.”