Association of serum globulin with all-cause mortality in incident hemodialysis patients

Abstract

Background Serum globulin is a major component of total protein and can be elevated in inflammatory disease states. While inflammation is common in hemodialysis patients and associated with mortality and morbidity, the association between serum globulin and mortality have never been examined in hemodialysis patients. Methods In a retrospective cohort of 104,164 incident hemodialysis patients treated by a large dialysis organization from 2007 to 2011, we explored the association between baseline serum globulin, A/G ratio and serum protein levels and all-cause, cardiovascular and infection-related mortality with adjustments for demographic variables and laboratory markers of malnutrition and inflammation using Cox proportional hazard models. Results Patients with globulin concentration >3.8 g/dL had higher all-cause and infection-related mortality risk (Hazard Ratio [HR] 1.11, 95% Confidence Interval [95%CI]: 1.06, 1.16 and HR 1.28, 95%CI: 1.09, 1.51; respectively) in the fully adjusted model when compared to the reference group of 3.0-<3.2 g/dL. In addition, patients with A/G ratio <0.75 had a 45% higher all-cause mortality hazard (HR 1.45, 95%CI: 1.38, 1.52) and patients with total serum protein <5.5 g/dL had a 34% higher risk of death (HR: 1.34, 95%CI: 1.27, 1.42) when compared to the reference (A/G ratio 1.05-<1.15 and total serum protein 6.5-<7 g/dL, respectively). Conclusions Among incident hemodialysis patients, higher globulin level was associated with higher mortality risk independent of other markers of malnutrition and inflammation, including albumin. Lower A/G ratio and serum protein was also associated with higher mortality hazard. The mechanisms that contribute to elevated serum globulin should be further explored.

Clinical significance of albumin to globulin ratio among patients with stroke-associated pneumonia

“…Furthermore, an in vitro experiment described albumin added to the albumin dialysis reduced the measurable amount of proinflammatory cytokine levels of IL-6, indicating albumin may also be an anti-inflammatory factor ( 21 ). Serum globulin, a classic inflammatory factor, increases during the inflammatory process ( 22 ). Inflammation typically causes an increase in the leukocytes.…”

Construction and validation of an early warning model for predicting the acute kidney injury in elderly patients with sepsis

“…In the stage of sepsis, albumin can indirectly contribute to immunity by providing nitrogen for globulin production, resulting in hypoalbuminemia and elevated globulin concentration [44]. Pai et al indicated that higher serum globulin (≥ 38 g/L) contributed to a higher infection-related mortality risk in 104,154 incident hemodialysis patients [45]. Thus, a lower AGR can result from a combination of low albumin and high globulin, and the combined biomarker might be a robust predictor of S-AKI in elderly sepsis patients.…”

Physical activity is associated with nutritional biomarkers in hemodialysis patients: A cross‐sectional study

“…In general, serum albumin is used to identify nutritional status, while serum globulin is used to assess the severity of chronic inflammation. As most biochemical markers, albumin, globulin, and albumin/globulin ratio levels are affected by several factors, such as fluid status [35][36][37] inflammatory acute changes, and nutritional status [15,[38][39][40][41]. Kaizu et al also demonstrated that muscle area was directly associated with serum albumin [42].…”

“…Our results did not demonstrate an association between physical activity levels and globulin. Despite no previous study have investigated this association, a recent cohort study found that high globulin levels were associated with mortality in CKD patients, a phenomenon that can be explained by conditions associated with inflammation (e.g., infections, malignancies, hematological disorders of connective tissue diseases, and increased immunoglobulin fraction) [15,43].…”

“…Previous evidence showed it to be associated with mortality [14]. In addition, globulin is also a major component of total protein, and has been recently associated with higher mortality risk independent of other nutritional biomarkers, such as albumin [15].…”