WHAT IS EARLY START AND WHY IT SHOULD NOT BE SYSTEMATIC? Christian Com be, Bordeaux, France

Transcription

1 WHAT IS EARLY START AND WHY IT SHOULD NOT BE SYSTEMATIC? Christian Com be, Bordeaux, France Chair: Mustafa Arici, Ankara, Turkey Bernard Canaud, Montpellier, France Prof Christian Combe Servic e de N éphrologie T rans plantation Dialys e Hopital P ellegrin C entre H os pitalier U nivers itaire de Bordeaux Bordeaux, Franc e Slide 1 Thank you Bernard. So I m supposed to speak about early start and m y friend Charlie Tom son will speak of late start but unfortunately, usually we agree and Jam es Tattersall will say what good dialysis is. So we have 10 m inutes to review what early start is. So I will be very brief. Slide 2

2 Early start is initiation of dialysis at an egfr of m ore than 10 m l/m in by the MDRD equation. So that s a definition that I take for m yself, it s from Rosansky and I would add that there is no clinical or biological need to com m ence dialysis. Slide 3 So, early start is a tendency in m any countries. For instance, in the US-RDS now m ore than 50% of patients begin dialysis at a GFR higher than 10 m l/m in. The European data are the sam e. Slide 4

3 If we look at the French data, we can see that the proportion of patients who begin dialysis at m ore than 10 m l/m in is increasing and m ean GFR diuresis start is increasing. The scale here is quite extended. Slide 5 So if people begin dialysis at high GFRs, can we m easure accurately renal function in CKD stage 5? This has been addressed in a nice study from the NECOSAD study. Slide 6

4 If we look at the MDRD equation in CKD stage 5 patients from Holland then we can see that there is a wide m argin of variation, especially at the tim e when decision is taken, that is you cannot rely entirely on this. Slide 7 Another point is that if you look at m uscle m ass, which is a determ inant of the production of creatinine, there is no relationship between m uscle m ass and m easured creatinine clearance. But if you look at the relationship between m uscle m ass and egfr, then the patients who have the lower m uscle m ass have the highest egfrs. That is in people who have low m uscle m ass, who are undernourished, then you m ay begin dialysis earlier because you have a m isestim ation of GFR. Slide 8

5 So the next question is: could we anticipate the decline of renal function, if we plan dialysis can we predict the evolution of renal function in CKD patients of stages 4 and 5? Slide 9 From this study from the group of Nancy, France you can see that in som e patients the decline in GFR is really linear. So in these patients you can predict that dialysis will be in x days or m onths. Slide 10

6 But in m any patients you have fluctuations which m ay be probably related to fluctuations in the hydration status of the patients and you cannot predict, so therefore you cannot say to a patient you will be on dialysis within 3 m onths, let s begin now. Slide 11 The next question is: is early start of dialysis associated with better survival? Slide 12

7 So the basic idea is that when renal function is altered, there is an increase in m ortality and specifically in cardiovascular m ortality. This has been extensively shown; in this aggregation of cohort studies you have m ore than 1 m illion patients. Slide 13 So the next step is to say that if you have a lower creatinine clearance, this has been shown for instance in the CANUSA study, the lower the creatinine clearance the poorer the survival of the patients who are beginning peritoneal dialysis. So this is true and intuitively you can say that with a creatinine clearance of zero you will have zero survivals. Slide 14

8 But the problem is that in this study as in others the type of creatinine clearance that you can achieve is not equivalent to having residual renal function and to having creatinine clearance achieved by peritoneal dialysis. Slide 15 So the concept of early dialysis start was m ade m ainly on this type of studies. So we needed as nephrologists random ised controlled studies. This has been done in the South hem isphere by the colleagues of Australia and New Zealand. They have designed the IDEAL study, Initiating Dialysis Early And Late. The design of their study was to have patients with early start m l/m in versus late start 5-7 m l/m in. Slide 16

9 Actually what they have achieved is a different of 2.2 m l/m in that is 12 versus 9.8 m l/m in. Not a very significant difference with a delay of dialysis which was significant of 7 m onths in the late start group. There is absolutely no difference between the early start and the late start group. So from this random ised controlled study, in which probably we have a lack of clinically significant power, there is no difference in m ortality in late versus early start but m any patients from the late start had to begin dialysis earlier. Slide 17 In m any registries, this is an exam ple from the French Registry, the beginning of dialysis at lower GFR is associated with a better survival. The patients who begin dialysis at high GFRs are usually the elderly that is the patients who have lost m uscle m ass, who produce less creatinine and they are the patients in whom egfr is not reliable. Slide 18

10 So is early start of dialysis associated with better outcom es in the elderly? Slide 19 So this is a study which was published in the New England Journal of Medicine 3 years ago in patients who were in nursing hom es and they had becom e dialysis at a egfr of 10.7 m l/m in. What happened to them? Many of them died and m any of them declined in term s of functional status. So in this study there was absolutely no evidence for an im provem ent in the functional status of these patients. Slide 20

11 However, we have to prepare dialysis. This is from patients from Brazil with different age groups and you have the outcom e of patients: they can survive without renal replacem ent therapy, they can be treated with renal replacem ent therapy or they can die without renal replacem ent therapy. So it s worth preparing dialysis even if you re not convinced of early start as I am. Slide 21 So to sum m arise, early start of dialysis relies on estim ations of renal functions linked in part to nutrition. It has not been shown in random ised controlled trials or observational studies to im prove outcom es in term s of m ortality, m orbidity, nutrition, quality of life, health expenditures. So it can be indicated in som e circum stances, for instance, preparation for transplant especially and thinking of polycystic kidney disease. It can be indicated when there are associated com orbidities, oedem a, urem ic syndrom e or whatever but in any case it should not be system atic but ESRD should be anticipated. Slide 22

12 I thank you for your attention and I think m y friend Charlie will answer this question: is late start better?