Clinique de Néphrologie-Dialyse, CHU Brugmann, Université Libre de Bruxelles, Brussels, Belgium
Correspondence and offprint requests to: Max Dratwa, Clinique de Néphrologie-Dialyse, CHU Brugmann, Université Libre de Bruxelles, 4 Place Van Gehuchten, B-1020 Brussels, Belgium.
`It's no good running fast, what counts is not starting late-' ... and with a belly full of dialysate.
Introduction
Despite improvements in dialytic therapy and hormonal replacement, patients with end-stage renal disease (ESRD) still display high morbidity and mortality. A variety of factors have been implicated. The burden of co-morbid conditions (cardiovascular disease, hypertension, anaemia, malnutrition, etc.) with which patients reach ESRD has great importance and requires interventions certainly several years before renal replacement therapy (RRT) is started. Factors more readily amenable to intervention by nephrologists include dialysis dose, pre-ESRD care, and timely initiation of dialysis. Improvement of dialysis adequacy by increasing the dose delivered by both haemodialysis (HD) and peritoneal dialysis (PD) has been a consistent trend of the past decade. Early referral to optimize pre-ESRD care remains a serious problem in Europe [1] but could certainly be improved by a concerted educational effort by nephrologists addressing non-nephrologists and the public.
When to start dialysis?
The right moment to start dialysis remains a matter of controversy even though the Dialysis Outcomes Quality Initiative (DOQI) of the National Kidney Foundation recommended starting dialysis earlier than today's common practice in order to improve the clinical outcomes for ESRD [2]. This new approach, designated the `Healthy Start' concept, postulates that the uraemic state is a progressive process that impacts on patients health long before classical uraemic symptoms are observed. The `Healthy Start' concept implies that more subtle and early manifestations of renal dysfunction, most notably malnutrition, are amenable to dialytic therapy. Indeed, it has been clearly demonstrated that nutritional status deteriorates as a result of decreased protein ingestion and increased catabolism as renal failure progresses [3,4]. In addition, the CANUSA study showed an association between the relative risk of death and nutritional parameters. Importantly, nutritional parameters improved after several months of PD [4,5]. Thus, it makes perfect sense to start RRT at a time when renal failure is advanced, but when uraemic patients do not yet show signs of malnutrition. When is that? The DOQI guidelines propose that one should start RRT when a renal Kt/V of 2.0 has been reached (equivalent to a creatinine clearance of 914 ml/min/1.73 m2) unless there are absolutely no signs of malnutrition or symptoms of uraemia. This value of 2.0 has been chosen because it has been linked to a reasonably good survival on CAPD. The continuous character of this dialytic modality renders it comparable to continuous renal function. After all, this approach is not too dissimilar from the rationale of starting erythropoietin therapy prior to ESRD. Despite its compelling attraction, however, the `Healthy Start' concept has not been received with great general enthusiasm, except by some opinion leaders. The reason is presumably that the rationale is based only on retrospective studies and indirect evidence. A multicentre European randomized prospective study is currently under way to test the validity of this approach by examining its impact on mortality, morbidity, residual renal function, quality of life, and social costs.
Which modality of dialysis to select?
If the nephrological community accepts the idea of an earlier, i.e. healthier, start of RRT, the question arises as to which dialytic modality to choose. The answer might also involve a departure from common practice habits. PD is selected as the first modality of RRT in only 1025% of patients starting dialysis in Western Europe (excluding UK). Nevertheless its results regarding patient survival are as good, if not better, as those of HD, in the first 3 years of therapy [6]. This is probably linked to the known favourable effect of PD on residual renal function. This longer preservation of residual renal function allows the patient a more liberal fluid/diet intake with the added psychological advantage of maintaining normal micturition. In addition, although this has recently been questioned, it may delay the development of dialysis amyloidosis by retarding the progressive increase in ß2 microglobulin plasma levels in PD patients compared to their HD counterparts. Furthermore, even though renal function is greatly diminished, it still makes a notable contribution to total clearance at this stage. It allows the maintenance of adequacy targets with lower numbers and/or volumes of exchanges, thus preserving quality of life by reducing the burden of manipulations. This approach has been designated `incremental dialysis'. Automated peritoneal dialysis has indeniable advantages with respect to quality of life. It has been recently suspected, however, that it reduces residual renal function faster than CAPD, but this point remains moot.
In any case, for both types of PD, every effort should be made not to jeopardize residual renal function: one should avoid nephrotoxic drugs or excessive ultrafiltration; in addition, the prescription of a loop diuretic can be useful. It does not improve clearances, but helps maintain fluid balance without resorting to too many exchanges with high concentrations of glucose. The latter can even be replaced with one long exchange of a 7.5% icodextrin solution (nightly for CAPD or daily for APD), which can produce significant ultrafiltration despite being iso-osmolar to plasma. Maintenance of residual renal function also seems to be an important factor for maintenance of sodium and water balance early in the course of PD, allowing for a normal extracellular volume and good control of blood pressure.
What are the advantages?
There are also other clear advantages of starting dialytic therapy with PD rather than HD. As with any home therapy, the risk of acquiring a blood-borne viral infection such as hepatitis C is evidently considerably less. From a quality of life point of view, PD seems superior to HD at the beginning of therapy; indeed a recent study [7] showed that mental health scores assessed by the SF-36 questionnaire 3 months after beginning dialysis were much closer to those of the general population for PD patients than for those starting on HD.
In addition, the outcome of transplantation is influenced by the type of preceding dialysis method; in a recent review, Van Biesen et al. [8] showed that immediate graft function was less frequently impaired in PD than in HD patients and one had to resort less frequently to dialysis in the post-transplantation period. Length of hospitalization and cost were less and there was a tendency to better long-term results.
For all these reasons, it is not surprising that starting RRT on PD is apparently advantageous with respect to survival as recently shown by Van Biesen et al. [9]. Using the Cox model, they demonstrated that patients starting on PD and transferred to HD for various reasons (infections, mechanical problems, inadequate clearance and/or ultrafiltration) after a mean period of 3.5 years had a significantly better overall survival than patients kept on their initial treatment of either mode. Obviously, starting with PD delays the use of vascular access, which remains the Achilles' heel of HD. From a societal point of view, PD is very cost-effective and is one answer to the financial and logistical constraints of a continuously increasing number of ESRD patients.
Conclusion
Common sense supported by scientific data indicates that patients with advanced chronic renal failure should be referred early to a nephrological team. Patients will then be provided with up-to-date means of controlling uraemic complications and will be educated in time about the different options of RRT. If medically suitable, they should be offered PD as the best first option, with transfer to transplantation whenever possible and to HD whenever needed. Whatever the choice, dialysis should be instituted early enough to avoid malnutrition and other sequelae of prolonged renal failure. This approach meets the three postulates recently put forward: timely referral, healthy start and integrated care of renal failure [10]. The time has come for the three modalities of RRT to be considered complementary and no longer competitive.
References
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