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Outcome predictability of biomarkers of protein-energy wasting and inflammation in moderate and advanced chronic kidney disease^1,2,3,4

¹ From the Salem VA Medical Center, Salem, VA (CPK); the University of Virginia, Charlottesville, VA (CPK); the Carilion Clinic, Roanoke, VA (SMG); The Johns Hopkins Bayview Medical Center, Baltimore, MD (JEA); the Harold Simmons Center for Kidney Disease Research and Epidemiology, Los Angeles Biomedical Research Institute at Harbor–UCLA Medical Center, Torrance, CA (KK-Z); and the David Geffen School of Medicine at UCLA, Los Angeles, CA (KKZ).

² Parts of this material were presented at the American Society of Nephrology Renal Week 2008, November 4–9, Philadelphia, PA.

³ Supported by grant 1R01DK078106-01 from the NIDDK of the NIH (to CPK and KK-Z).

⁴ Address correspondence to CP Kovesdy, Division of Nephrology, Salem VA Medical Center, 1970 Roanoke Boulevard, Salem, VA 24153. E-mail: csaba.kovesdy{at}va.gov.

Background: Markers of protein-energy wasting (PEW) and inflammation are common in chronic kidney disease (CKD) and are among the strongest predictors of mortality in dialysis patients.

Objective: We hypothesized that markers of PEW and inflammation show similar associations in patients with non-dialysis-dependent CKD (NDD-CKD).

Design: We examined the associations of serum albumin, white blood cell (WBC) count, percentage of lymphocytes in WBCs (%LYM), and a combination of all 3 with all-cause mortality and with the composite of predialysis mortality or end-stage renal disease (ESRD) by using fixed-covariate and time-dependent Cox models in 1220 men with NDD-CKD.

Results: Lower albumin and %LYM and a higher WBC count were significantly associated with outcomes. In time-dependent Cox models, compared with patients in whom none of these markers indicated PEW, those in whom 1, 2, or all 3 markers indicated the presence of PEW had multivariable-adjusted hazard ratios (95% CI) for all-cause mortality of 1.7 (1.2, 2.4), 2.4 (1.7, 3.4), and 3.6 (2.5, 5.1); the P for trend was <0.001. Similar associations were present in fixed-covariate models for all-cause mortality and in fixed-covariate and time-dependent models for the composite outcome.

Conclusions: Traditional and nontraditional markers of PEW display robust, strong, and independent associations with mortality in patients with NDD-CKD. Clinical trials are warranted to examine whether PEW-improving interventions can lead to better outcomes in these patients.