Association of lactate dehydrogenase with mortality in incident hemodialysis patients

Abstract

Background: Lactate dehydrogenase (LDH) plays a role in the glucose metabolism of the human body. Higher LDH levels have been linked to mortality in various cancer types; however, the relationship between LDH and survival in incident hemodialysis (HD) patients has not yet been examined. We hypothesized that higher LDH level is associated with higher death risk in these patients.

Methods: We examined the association of baseline and time-varying serum LDH with all-cause, cardiovascular and infection-related mortality among 109 632 adult incident HD patients receiving care from a large dialysis organization in the USA during January 2007 to December 2011. Baseline and time-varying survival models were adjusted for demographic variables and available clinical and laboratory surrogates of malnutrition-inflammation complex syndrome.

Results: There was a linear association between baseline serum LDH levels and all-cause, cardiovascular and infection-related mortality in both baseline and time-varying models, except for time-varying infection-related mortality. Adjustment for markers of inflammation and malnutrition attenuated the association in all models. In fully adjusted models, baseline LDH levels ≥360 U/L were associated with the highest risk of all-cause mortality (hazard ratios = 1.19, 95% confidence interval 1.14-1.25). In time-varying models, LDH >280 U/L was associated with higher death risk in all three hierarchical models for all-cause and cardiovascular mortality.

Conclusions: Higher LDH level >280 U/L was incrementally associated with higher all-cause and cardiovascular mortality in incident dialysis patients, whereas LDH <240 U/L was associated with better survival. These findings suggest that the assessment of metabolic functions and monitoring for comorbidities may confer survival benefit to dialysis patients.

Keywords: all-cause mortality; end-stage renal disease; hemodialysis; lactate dehydrogenase.

FIGURE 1

Baseline all-cause (A), cardiovascular (B) and infection-related (C) mortality, and time-varying all-cause (D), cardiovascular (E) and infection-related (F) mortality HRs (and 95% CI error bars) by LDH levels across three levels of multivariable adjustment in 109 632 incident HD patients.

FIGURE 2

Subgroup analysis of all-cause mortality hazard ratios (and 95% CI error bars) of baseline (A) and time-varying (B) high LDH (LDH ≥250 U/L) versus low LDH (LDH <250 U/L) after adjustment for casemix + MICS variables. AST, aspartate aminotransferase; CBVD, cerebrovascular disease; COPD, chronic obstructive pulmonary disease; Hgb, hemoglobin; HIV, human immunodeficiency virus.