Renal Kt/Vurea and PNAn: “New” Criteria for the Initiation of Chronic Dialysis

The nephrology community has come a long way since the first patient received hemodialysis as a form of renal replacement therapy. Numerous advances have taken place in the technological aspects of the dialysis procedure since then. There is no doubt that renal replacement therapy is lifesaving in the short term. However, when one looks at long-term mortality statistics from large databases such as the USRDS, it is clear that much remains to be done. The annual adjusted mortality rate of the U.S. dialysis patients has dropped from 26.2 deaths/100 patient years in 1989 to 22.3 deaths/100 patient years in 1996 (1). This is encouraging in the face of an older and more diabetic end-stage renal disease (ESRD) population. The reasons for this improvement have been a matter of some speculation and may include an impact of the general progress made in the management of comorbid conditions (diabetes, hypertension, hyperlipidemia, and cardiovascular disease), improved attention to the dose of dialysis, and the use of biocompatible membranes. However, if one looks at mortality with the perspective of the “expected remaining life” parameter, the results suggest that a chronic dialysis patient is more like someone with a malignancy, with a severely compromised life expectancy (2). Cardiovascular causes, particularly coronary artery disease, continue to be responsible for more than 50% of deaths (3). In fact, it has been said that the incidence of cardiovascular disease in both chronic renal insufficiency and dialysis populations is of epidemic proportions (4). Left ventricular hypertrophy (LVH) is already present in more than 70% of patients before the commencement of dialysis (5). Knowing that LVH is a predictor of death in the dialysis patient, it can be said that the die may already have been cast with respect to morbidity and mortality even before the patient is started on dialysis. The link between malnutrition and cardiovascular disease is only beginning to be unraveled. A recent review by Bergstrom and Lindholm (6) puts this in perspective and suggests that a variety of cytokines may be the link between fluid overload and hypertension on the one hand, and infection, inflammation, and malnutrition on the other, all inextricably linked with atherosclerosis, the underlying lesion in most vascular occlusions. Malnutrition may thus only be a surrogate marker for the progressive chronic inflammatory state that uremia is thought to be (along with other comorbidities that may cause anorexia by themselves), and indeed may not be correctable simply by the provision of nutrients. One aspect that has only recently begun to receive the attention it deserves is the issue of the timing of initiation of dialysis (7–10). This in part determines the success of dialysis therapy even before it is started. It is our strong belief that if the paradigm is shifted to initiating all renal replacement therapy when the patient is in a state of relatively better preserved overall health, we could possibly achieve superior results with dialysis modalities that have seen continued technological advancements and are less and less a health risk themselves, although this latter contention is not universally accepted (11). In other words, if the superior technology is applied to the patient when the latter is relatively better preserved in terms of nutritional status and comorbidity, the outcomes are likely to improve. The emphasis so far has been on the technology and not as much on the timing of its initiation (12). Of course, any strategy involving the more timely initiation of dialysis should be part of an overall improvement in the care of the patient with progressive chronic renal disease, and it is notable that there is a relative paucity of literature dedicated to the organized care of the pre-ESRD patient and a complete absence of any pre-ESRD registry at the national level (13), although there are moves at the national level to rectify this situation. Tattersall et al. (14) were the first to estimate their patients’ residual renal function predialysis using the urea kinetic modeling approach [urea clearance ( Kt in liters per week) corrected to the total body water ( V in liters), i.e.,Kt/Vurea] and to point out that the mean renal Kt/Vurealevel at dialysis therapy initiation in their group Address correspondence to: Karl D. Nolph, MD, Division of Nephrology, Department of Internal Medicine, University of Missouri, MA436 Health Sciences Center, Columbia, MO 65212-0001. E-mail: nolphk@health.missouri.edu Seminars in Dialysis—Vol 12, Suppl 1 (May–June) 1999 pp. S-61–S-65