The obesity paradox and mortality associated with surrogates of body size and muscle mass in patients receiving hemodialysis

Abstract

Objective: To determine whether dry weight gain accompanied by an increase in muscle mass is associated with a survival benefit in patients receiving maintenance hemodialysis (HD).

Patients and methods: In a nationally representative 5-year cohort of 121,762 patients receiving HD 3 times weekly from July 1, 2001, through June 30, 2006, we examined whether body mass index (BMI) (calculated using 3-month averaged post-HD dry weight) and 3-month averaged serum creatinine levels (a likely surrogate of muscle mass) and their changes over time were predictive of mortality risk.

Results: In the cohort, higher BMI (up to 45) and higher serum creatinine concentration were incrementally and independently associated with greater survival, even after extensive multivariate adjustment for available surrogates of nutritional status and inflammation. Dry weight loss or gain over time exhibited a graded association with higher rates of mortality or survival, respectively, as did changes in serum creatinine level over time. Among the 50,831 patients who survived the first 6 months and who had available data for changes in weight and creatinine level, those who lost weight but had an increased serum creatinine level had a greater survival rate than those who gained weight but had a decreased creatinine level. These associations appeared consistent across different demographic groups of patients receiving HD.

Conclusion: In patients receiving long-term HD, larger body size with more muscle mass appears associated with a higher survival rate. A discordant muscle gain with weight loss over time may confer more survival benefit than weight gain while losing muscle. Controlled trials of muscle-gaining interventions in patients receiving HD are warranted.

FIGURE 1.

Time-dependent associations between 3-month–averaged dry weight adjusted for height, known as body mass index (BMI), and 5-year (July 1, 2001, through June 30, 2006) mortality in 121,762 patients receiving hemodialysis (HD). Cox regression–based hazard ratios of death are represented by unfilled circles for the unadjusted model, filled circles for the model adjusted for case mix, and unfilled triangles for models adjusted for case mix and the malnutrition-inflammation-cachexia syndrome (MICS). Error bars represent 95% confidence intervals. Case-mix–adjusted models include adjustment for age, sex, diabetes mellitus, standardized mortality ratio, race, vintage, primary insurance, marital status, dialysis dose, dialysis catheter, and baseline comorbid states. The MICS model covariate includes all case-mix covariates plus urea kinetics–calculated protein catabolic rate (normalized protein nitrogen appearance or normalized protein catabolic rate), serum levels of albumin, total iron-binding capacity, white blood cell (WBC) count, percentage of lymphocytes, as well as calcium, phosphorous, bicarbonate, and ferritin levels.

FIGURE 2.

Change in dry weight during the first 6 months of the cohort as a predictor of mortality in 57,247 patients receiving hemodialysis (HD) who survived through the first 2 calendar quarters of the cohort and for whom post-HD dry-weight values for the 6 consecutive months were available. Compared with patients with stable weight (dry weight gain or loss of <1%), a graded decline in dry weight was associated with an increase in the subsequent risk of death, whereas weight gain over 6 months was incrementally associated with a greater 5-year survival rate. Cox regression–based hazard ratios of death are represented by unfilled circles for the unadjusted model, filled circles for the model adjusted for case mix, and unfilled triangles for models adjusted for case mix and the malnutrition-inflammation-cachexia syndrome (MICS). Error bars represent 95% confidence intervals. See legend of Figure 1 for the list of covariates in multivariate adjustment.

FIGURE 3.

Time-dependent associations between 3-month–averaged serum creatinine concentrations before hemodialysis, as a surrogate of muscle mass, and 5-year (July 1, 2001, through June 30, 2006) mortality in 107,082 patients receiving hemodialysis. Cox regression–based hazard ratios of death are represented by unfilled circles for the unadjusted model, filled circles for the model adjusted for case mix, and unfilled triangles for models adjusted for case mix and the malnutrition-inflammation-cachexia syndrome (MICS). Error bars represent 95% confidence intervals. See legend of Figure 1 for the list of covariates in multivariate adjustment.

FIGURE 4.

Change in serum creatinine concentration (a surrogate of change in muscle mass) during the first 6 months of the cohort as a predictor of mortality in 58,201 patients receiving hemodialysis (HD) who survived through the first 2 calendar quarters of the cohort and for whom pre-HD serum creatinine values for the 6 consecutive months were available. Compared with patients with stable serum creatinine concentrations (dry weight gain or loss of <1%), patients with a graded decline in dry weight had an increased risk of subsequent death, whereas weight gain during the 6 months was incrementally associated with greater 5-year survival. An increase or decrease in serum creatinine levels during the first 6 months was associated with parallel changes in subsequent survival in the entire cohort. Cox regression–based hazard ratios of death are represented by unfilled circles for the unadjusted model, filled circles for the model adjusted for case mix, and unfilled triangles for models adjusted for case mix and the malnutrition-inflammation-cachexia syndrome (MICS). Error bars represent 95% confidence intervals. See legend of Figure 1 for the list of covariates in multivariate adjustment.

FIGURE 5.

A combination of changes in dry weight and serum creatinine level during the first 6 months of the cohort as a predictor of mortality in 50,831 patients receiving hemodialysis (HD) across different demographic subgroups. The discordant group of an increase in dry weight accompanied by a decrease in serum creatinine levels is the reference group in all analyses. Cox regression–based hazard ratios of death are represented by unfilled circles for the unadjusted model, filled circles for the model adjusted for case mix, and unfilled triangles for models adjusted for case mix and the malnutrition-inflammation-cachexia syndrome (MICS). Error bars represent 95% confidence intervals. See legend of Figure 1 for the list of covariates in multivariate adjustment. Cr = serum creatinine; ref = reference; Wt = weight.