The objective of this study was to analyze risk factors affecting mortality rates (MR) in hemodialysis patients undergoing shortened dialysis time who were regularly kinetically modeled. Over a 14-month period, 180 in-center hemodialysis patients, 54% male, 46% female, 57% Black, 39% Caucasian, and 4% Hispanic, treated with rapid high efficiency dialysis (RHED = 2-3 h, 3 times/ week) and conventional dialysis (3-4 h, 3 times/week) were studied. Median patient age was 56.7 years (16-84 years) and dialysis care ranged from 6 months to 18 years (mean ± SD = 4.0 ± 4.2 years). The patients underwent monthly urea kinetic modeling. The dialysis prescription was based upon normalizing Kt/V between 0.8 and 1.2 and the protein catabolic rate (PCRn) between 0.9 and 1.1. Thirty-three percent of the patients received recombinant human erythropoietin (r-HuEPO). The effects of various covariates, including primary diagnosis, post/predialysis BUN ratios, creatinine, albumin, calcium, phosphate, cholesterol, hemoglobin, r-HuEPO, Kt/V, and PCRn were analyzed using analysis of variance, χ2 and linear discriminant function (DF) statistical methods. Several significant factors emerged as influencing outcome. The DF analysis produced a highly statistically significant (p 3.5 g/dl), higher postdialysis BUN, creatinine, and cholesterol levels, and use of r-HuEPO. The use of r-HuEPO when analyzed by DF significantly improved MR, 8.3% as opposed to 19.2%. It is concluded that urea kinetic modeling permits shortening dialysis times without affecting mortality or hospitalization rates, and that low postdialysis BUN, post/predialysis BUN ratios, creatinine, and albumin values are correlated with a lower chance of survi