Early Referral to the Nephrologist and Timely Initiation of Renal Replacement Therapy: A Paradigm Shift in the Management of Patients With Chronic Renal Failure Gregorio T. Obrador, MD, and Brian J.G. Pereira, MD, DM ● The high mortality rate among dialysis patients has spawned investigation into potentially correctable factors that are associated with an increased risk of death. Several studies have demonstrated a strong association between an increased risk of death in dialysis patients and suboptimal delivered dose of dialysis, malnutrition, and non-renal comorbidity. In addition, the use of unsubstituted cellulose dialyzers and reprocessed dialyzers also has been associated with an increased risk of death. Increased attention to these factors has resulted in a significant improvement in patient survival. Nonetheless, the mortality of dialysis patients remains unacceptably high and indicates that other factors may be operative. One of the factors that has thus far received scant attention, but could significantly affect morbidity and mortality in dialysis patients, is the timing and quality of care before initiation of dialysis. Optimal pre–end-stage renal disease care involves early interventions aimed at delaying progression of chronic renal failure, judicious management of uremic complications, timely placement of vascular access, timely initiation of renal replacement therapy, and implementation of educational programs targeted at maximum rehabili- tation. Given the fact that early referral to the nephrologist is likely to result in optimal pre-dialysis care, the 1993 National Institutes of Health Consensus Statement on Morbidity and Mortality of Dialysis recommended that referral of a patient to a renal team should occur at a serum creatinine of 1.5 mg/dL in women and 2.0 mg/dL in men. Several investigators also have argued that patients with chronic renal failure who begin dialysis at a relatively ‘‘high level of residual renal function’’ (early start) may have lower morbidity and mortality compared with patients who begin dialysis at a more traditional ‘‘low level of renal function’’ (late start). This hypothesis is based on evidence that declining renal function is associated with malnutrition and that malnutrition at the start of dialysis is associated with poor clinical outcomes. Furthermore, patients are started on dialysis at an endogenous solute clearance that is lower than that accepted as optimum for patients on dialysis. Finally, limited clinical studies have demonstrated the benefit of early initiation of dialysis. Consequently, the Peritoneal Dialysis Adequacy Work Group of the National Kidney Foundation–Dialysis Outcomes Quality Initiative recommends that dialysis be initiated when the weekly renal Kt/V urea decreases to below 2.0 unless all three of the following criteria are fulfilled: (1) stable or increased edema-free body weight, (2) normalized protein equivalent of total nitrogen appearance greater than 0.8, and (3) absence of clinical symptoms and signs attributable to uremia.  1998 by the National Kidney Foundation, Inc. INDEX WORDS: Kidney failure; renal replacement therapy; dialysis; referral; hospitalization; cost; mortality; vascular access; malnutrition. T HE end-stage renal disease (ESRD) pro- gram in the United States has grown from approximately 10,000 beneficiaries in 1973, when the Medicare entitlement became effective, to 86,354 in 1983, and to 257,266 as of December 31, 1995. 1,2 These figures represent a more than doubling in the prevalence of ESRD during the last decade, an annual increase of approximately 9%. The increasing prevalence of treated ESRD can be attributed primarily to the rapid increase in the incidence of treated ESRD, which cur- rently stands at 262 per million population. 2 Despite recent data suggesting that the incidence rate of treated ESRD may be slowing down, the pattern is still one of continued growth. Indeed, analysis conducted by the Health Care Financing Administration suggests that by the turn of the century, more than 300,000 patients will be enrolled in the ESRD program. 3 Patients with ESRD experience significantly greater morbidity, including a substantial decline in the quality of life. The frequency and duration of hospitalization has been used as a measure of morbidity or as an objective measure of quality of life because of the impact that it can have on the lifestyle of patients. 4,5 According to US Renal Data System (USRDS) data, the mean number of admissions during 1995 was 1.3 for patients younger than 65 years and 1.4 for patients older than 65 years. The average hospital days per year From the Division of Nephrology, New England Medical Center, Boston, MA. Received July 2, 1997; accepted in revised form Septem- ber 19, 1997. Address reprint requests to Brian J.G. Pereira, MD, DM, Division of Nephrology, Box 391, New England Medical Center, 750 Washington St, Boston, MA 02111. E-mail: brian.pereira@es.nemc.org  1998 by the National Kidney Foundation, Inc. 0272-6386/98/3103-0002$3.00/0 398 American Journal of Kidney Diseases, Vol 31, No 3 (March), 1998: pp 398-417