Mortality prediction by surrogates of body composition: an examination of the obesity paradox in hemodialysis patients using composite ranking score analysis

Abstract

In hemodialysis patients, lower body mass index and weight loss have been associated with higher mortality rates, a phenomenon sometimes called the obesity paradox. This apparent paradox might be explained by loss of muscle mass. The authors thus examined the relation to mortality of changes in dry weight and changes in serum creatinine levels (a muscle-mass surrogate) in a cohort of 121,762 hemodialysis patients who were followed for up to 5 years (2001-2006). In addition to conventional regression analyses, the authors conducted a ranking analysis of joint effects in which the sums and differences of the percentiles of change for the 2 measures in each patient were used as the regressors. Concordant with previous body mass index observations, lower body mass, lower muscle mass, weight loss, and serum creatinine decline were associated with higher death rates. Among patients with a discordant change, persons whose weight declined but whose serum creatinine levels increased had lower death rates than did those whose weight increased but whose serum creatinine level declined. A decline in serum creatinine appeared to be a stronger predictor of mortality than did weight loss. Assuming residual selection bias and confounding were not large, the present results suggest that a considerable proportion of the obesity paradox in dialysis patients might be explained by the amount of decline in muscle mass.

Figure 1.

Association of baseline body mass index (BMI, measured as weight (kg)/height (m)² and derived from 3-month averaged dry weight) with mortality in 121,762 hemodialysis patients over 5 years (July 2001–June 2006). The y-axes show the rate ratios of all-cause mortality over 5 years based on the spline model, adjusted for case mix and malnutrition-inflammation-complex syndrome. Models were adjusted for age, sex, diabetes mellitus, dialysis vintage, primary insurance, marital status dialysis dose, residual renal function, serum albumin, transferrin, ferritin, phosphorus, calcium, bicarbonate, peripheral white blood cell count, lymphocyte percentage, hemoglobin, and daily protein intake. Dashed lines are 95% pointwise confidence bands.

Figure 2.

Association of 3-month averaged prehemodialysis serum creatinine levels with mortality in 107,082 hemodialysis patients, 2001–2006. The y-axes show the rate ratios of all-cause mortality over 5 years based on the spline model, adjusted for case mix and malnutrition-inflammation-complex syndrome. Models were adjusted for age, sex, diabetes mellitus, dialysis vintage, primary insurance, marital status dialysis dose, residual renal function, serum albumin, transferrin, ferritin, phosphorus, calcium, bicarbonate, peripheral white blood cell count, lymphocyte percentage, hemoglobin, and daily protein intake. Dashed lines are 95% pointwise confidence bands.

Figure 3.

Association between mortality and change in dry weight (measured using body mass index (weight (kg)/height (m)²)) over the first 6 months of the study in 57,247 hemodialysis patients who survived through the first 2 calendar quarters of the study and for whom posthemodialysis dry weight values for 6 consecutive months were available, 2001–2006. The y-axes show the rate ratios of all-cause mortality over 5 years based on the spline model, adjusted for case mix and malnutrition-inflammation-complex syndrome. Models were adjusted for age, sex, diabetes mellitus, dialysis vintage, primary insurance, marital status, dialysis dose, residual renal function, serum albumin, transferrin, ferritin, phosphorus, calcium, bicarbonate, peripheral white blood cell count, lymphocyte percentage, hemoglobin, and daily protein intake. Changes are ranked as −100th to 0th percentiles for decline and 0th to 100th percentiles for increases. Dashed lines are 95% pointwise confidence bands.

Figure 4.

Association between mortality and changes in serum creatinine over the patients’ first 6 months in the study in 58,201 hemodialysis patients who survived through the first 2 calendar quarters and for whom prehemodialysis serum creatinine values for 6 consecutive months were available, 2001–2006. The y-axes show the rate ratios of all-cause mortality over 5 years based on the spline model, adjusted for case mix and malnutrition-inflammation-complex syndrome. Models were adjusted for age, sex, diabetes mellitus, dialysis vintage, primary insurance, marital status, dialysis dose, residual renal function, serum albumin, transferrin, ferritin, phosphorus, calcium, bicarbonate, peripheral white blood cell count, lymphocyte percentage, hemoglobin, and daily protein intake. Changes are ranked as −100th to 0th percentiles for decline and 0th to 100th percentiles for increases. Dashed lines are 95% pointwise confidence bands.

Figure 5.

Association of mortality with changes in dry weight (measured using body mass index (weight (kg)/height (m)²)) and serum creatinine over the first 6 months of the cohort in 50,831 hemodialysis patients. Each patient first received a percentile score between −100 and 100 according to the percentile rank of the change in dry weight or serum creatinine. The sum of scores resulted in a number between −200 and 200 (A), as did the difference (B). The y-axes show the rate ratios of all-cause mortality over 5 years based on the spline model, adjusted for case mix and malnutrition-inflammation-complex syndrome. Models were adjusted for age, sex, diabetes mellitus, dialysis vintage, primary insurance, marital status, dialysis dose, residual renal function, serum albumin, transferrin, ferritin, phosphorus, calcium, bicarbonate, peripheral white blood cell count, lymphocyte percentage, hemoglobin, and daily protein intake. Dashed lines are 95% pointwise confidence bands.