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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. Mayo Clin Proc. 2010;85(11):991-1001From the harold simmons center for chronic disease Research and epidemiology (K.K.-Z., e.s., j.j., n.n.) and division of nephrology and hypertension (K.K.-Z., j.d.K., R.M.), los angeles biomedical Research institute at harborucla Medical center, torrance, ca; ucla david Geffen school of Medicine (K.K.-Z., a.R.n., j.d.K., R.M.); department of Family health and/or epidemiology, ucla school of Public health, los angeles, ca (K.K.-Z., e.s., j.d.K.); salem veterans affairs Medical center, salem, va (c.P.K.); davita, el segundo, ca (a.R.n, M.K.); university of alberta, edmonton, alberta, canada (a.O.); and charité university school of Medicine, berlin, Germany and centre for clinical and basic Research, iRccs san Raffaele, Rome, italy (s.d.a.) the study was supported by dr Kalantar-Zadeh's research grants from the national institute of diabetes and digestive and Kidney diseases of the national institutes of health (R01 dK078106), the american heart association (0655776Y), and davita clinical Research (dcR), as well as a philanthropic grant from Mr harold simmons and an additional dcR grant for the division of nephrology & hypertension at harbor-ucla Medical center. drs nissenson and Krishnan are employees of davita. dr Kalantar-Zadeh is the medical director ...

In the general population, obesity is associated with increased cardiovascular risk and decreased survival. In patients with end-stage renal disease (ESRD), however, an “obesity paradox” or “reverse epidemiology” (to include lipid and hypertension paradoxes) has been consistently reported, i.e. a higher body mass index (BMI) is paradoxically associated with better survival. This survival advantage of large body size is relatively consistent for hemodialysis patients across racial and regional differences, although published results are mixed for peritoneal dialysis patients.. Recent data indicate that both higher skeletal muscle mass and increased total body fat are protective, although there are mixed data on visceral (intra-abdominal) fat. The obesity paradox in ESRD is unlikely to be due to residual confounding alone and has biologic plausibility. Possible causes of the obesity paradox include protein-energy wasting and inflammation, time discrepancy among competitive risk factors (undernutrition versus overnutrition), hemodynamic stability, alteration of circulatory cytokines, sequestration of uremic toxin in adipose tissue, and endotoxin-lipoprotein interaction. The obesity paradox may have significant clinical implications in the management of ESRD patients especially if obese dialysis patients are forced to lose weight upon transplant wait-listing. Well-designed studies exploring the causes and consequences of the reverse epidemiology of cardiovascular risk factors, including the obesity paradox, among ESRD patients could provide more information on mechanisms. These could include controlled trials of nutritional and pharmacologic interventions to examine whether gain in lean body mass or even body fat can improve survival and quality of life in these patients.

Background Maintenance hemodialysis is typically prescribed thrice-weekly irrespective of patient's residual kidney function (RKF). We hypothesized that a less frequent schedule at hemodialysis initiation is associated with greater preservation of RKF without compromising survival among patients with substantial RKF. Study Design A longitudinal cohort Setting & Participants 23,645 patients who initiated maintenance hemodialysis in a large dialysis organization in the United States (1/2007–12/2010), who had available RKF data during the first 91 days (or quarter) of dialysis, and who survived the first year. Predictor Incremental (routine twice-weekly for >6 continuous weeks during the first 91 days upon transition to dialysis) versus conventional (thrice-weekly) hemodialysis regimens during the same time. Outcomes Changes in renal urea clearance (KRU) and urine volume (UV) during one year after the first quarter, and survival after the first year. Results Among 23,645 included patients, 51% had substantial KRU (≥3.0 mL/min/1.73m2) at baseline. Compared to 8,068 patients with conventional hemodialysis regimen matched based on baseline KRU, UV, age, gender, diabetes, and central venous catheter use, 351 patients with incremental regimen exhibited 16% (95% CI, 5%-28%) and 15% (95% CI, 2%-30%) more preserved KRU and UV at second quarter, respectively, which remained across the following quarters. Incremental regimen showed higher mortality risk in patients with inadequate baseline KRU (≤3.0 mL/min/1.73m2; HR, 1.61; 95% CI, 1.07-2.44), but not in those with higher baseline KRU (HR, 0.99; 95% CI, 0.76-1.28). Results were similar in subgroup defined by baseline UV of 600 mL/day. Limitations Potential selection bias and wide CIs. Conclusions Among incident hemodialysis patients with substantial RKF, incremental hemodialysis may be a safe treatment regimen and associated with greater preservation of RKF while higher mortality is observed after a year in those with lowest RKF. Clinical trials are needed to examine safety and effectiveness of twice-weekly hemodialysis.