Resting Energy Expenditure and Subsequent Mortality Risk in Peritoneal Dialysis Patients ANGELA YEE-MOON WANG,* MANDY MAN-MEI SEA, † NELSON TANG, ‡ JOHN E. SANDERSON,* SIU-FAI LUI,* PHILIP KAM-TAO LI,* and JEAN WOO † *Department of Medicine & Therapeutics, † Center for Nutritional Studies, ‡ Department of Chemical Pathology, Prince of Wales Hospital, Chinese University of Hong Kong, Shatin. N.T., Hong Kong Abstract. Cardiovascular disease is the leading cause of death in ESRD patients and is strongly associated with malnutrition. The mechanism of malnutrition is not clear, but hypermetab- olism is suggested to contribute to cardiac cachexia. This study examined resting energy expenditure (REE) in relation to the clinical outcomes of ESRD patients who receive continuous ambulatory peritoneal dialysis (CAPD) treatment. A prospec- tive observational cohort study was performed in 251 CAPD patients. REE was measured at study baseline using indirect calorimetry together with other clinical, nutritional, and dialy- sis parameters. Patients were followed up for a mean  SD duration of 28.7  14.3 mo. REE was 39.1  9.6 and 40.1  9.0 kcal/kg fat-free edema-free body mass per day for men and women, respectively (P = 0.391). Using multiple regression analysis, fat-free edema-free body mass–adjusted REE was negatively associated with residual GFR (P  0.001) and serum albumin (P = 0.046) and positively associated with diabetes (P = 0.002), cardiovascular disease (P = 0.009), and C-reactive protein (P = 0.009). At 2 yr, the overall survival was 63.3, 73.6, and 95.9% (P  0.0001), and cardiovascular event-free survival was 72.3, 84.6, and 97.2% (P = 0.0003), respectively, for patients in the upper, middle, and lower ter- tiles of REE. Adjusting for age, gender, diabetes, and cardio- vascular disease, patients in the upper and middle tertiles showed a 4.19-fold (95% confidence interval, 2.15 to 8.16; P  0.001) and a 2.90-fold (95% confidence interval, 1.49, 5.63; P = 0.002) respective increase in the risk of all-cause mortality compared with those in the lower tertile. However, the signif- icance of REE in predicting mortality was gradually reduced when additional adjustment was made for C-reactive protein, serum albumin, and residual GFR in a stepwise manner. In conclusion, a higher REE is associated with increased mortal- ity and cardiovascular death in CAPD patients and is partly related to its close correlations with residual kidney function, cardiovascular disease, inflammation, and malnutrition in these patients. Malnutrition is usually the consequence of energy imbalance and can be attributed to changes in dietary intake or energy expendi- ture or both. Sustained hypermetabolism can lead to energy im- balance and wasting if not compensated for by an increase in energy intake. Indeed, hypermetabolism was suggested to be one of the contributory factors for cachexia in disease states such as cardiac failure (1), chronic obstructive pulmonary disease (2), and malignancy (3,4). However, its association with protein-energy malnutrition in ESRD patients has not been established. Protein-energy malnutrition is a significant complication and predicts mortality in ESRD patients (5,6). However, malnutrition is well known to be associated with inflammation and atheroscle- rotic vascular disease in ESRD patients (7,8). Whereas the sever- ity of inflammation as denoted by the acute-phase response or proinflammatory cytokine is related to resting hypermetabolism in diseases such as AIDS (9), chronic obstructive pulmonary disease (10), and malignancy (4), it is not known whether a higher resting energy expenditure (REE) is also a marker of inflammation or malnutrition in ESRD patients, in whom high prevalence of these complications is observed. Studies that examined REE in patients with ESRD showed conflicting data. Ikizler et al. (11) reported resting hypermetabo- lism in chronic hemodialysis patients that was noted to increase further during hemodialysis procedure. Recent study showed higher REE in patients who receive dialysis, regardless of the modality, than chronic renal failure patients who did not yet require dialysis (12). Conversely, other studies showed that REE of chronic renal failure patients were either reduced (13) or no different from normal control subjects (14,15). In this prospective follow-up study, we evaluated factors associated with REE in a large cohort of ESRD patients who were receiving continuous ambulatory peritoneal dialysis (CAPD) therapy and determined whether a single measurement of REE is related to the clinical outcomes of these peritoneal dialysis (PD) patients. Materials and Methods Study Population This study was approved by the Human Research Ethics Commit- tee of the Chinese University of Hong Kong. Altogether, 251 patients who were receiving CAPD treatment for 3 mo were recruited from Received May 27, 2004. Accepted August 17, 2004. Correspondence to Dr. Angela Yee-Moon Wang, Department of Medicine & Therapeutics, Prince of Wales Hospital, Chinese University of Hong Kong, Shatin, N.T. Hong Kong. Phone: 852-2632-3023; Fax: 852-2637-5396; E- mail: awang@cuhk.edu.hk 1046-6673/1512-3134 Journal of the American Society of Nephrology Copyright © 2004 by the American Society of Nephrology DOI: 10.1097/01.ASN.0000144206.29951.B2 J Am Soc Nephrol 15: 3134–3143, 2004