Nephrology Dialysis Transplantation Children's Unit, Strasbourg, France
Correspondence and offprint requests to: Prof. Michel Fischbach, Nephrology Dialysis Transplantation Children's Unit, Hospital de Hautepierre, Avenue Moliere, 67098 Strasbourg, France. Email: Michel.Fischbach{at}chru-strasbourg.fr
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Abstract |
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Methods. In this single-centre, observational, prospective, non-randomized study, five oligoanuric dialysis patients (mean age: 13.8 ± 3.2 years) were converted from standard on-line haemodiafiltration (S-OL-HDF) (4 h, three times/week) to daily on-line haemodiafiltration (D-OL-HDF) (3 h, six times/week). Patient selection was based on both the presence of uraemic cardiomyopathy (left ventricular hypertrophy and reduced fractional shortening) and their reduced therapeutic compliance. The D-OL-HDF parameters were the same as for the S-OL-HDF.
Results. Increasing the number of sessions from three to six weekly positively impacted the weekly dialysis dose. On D-OL-HDF, mean arterial blood pressure decreased significantly (from 95 ± 15 to 82 ± 13 and 87 ± 9 mmHg at 6 and 12 months, respectively). Left ventricular hypertrophy decreased and its fractional shortening improved markedly (from 26.6 ± 17% to 31 ± 14% and 46.6 ± 15% at 6 and 12 months, respectively). Pre-dialytic plasma phosphorus also decreased markedly (from 1.87 ± 0.23 to 1.43 ± 0.22 and 1.28 ± 0.29 mmol/l at 6 and 12 months, respectively), as did the calciumphosphorus product. The post-dialytic recovery time disappeared and so did perception of fatigue. Fasting the day before dialysis to avoid excess weight gain (necessitating longer dialysis) disappeared. Combined with an improved appetite, these changes resulted in higher caloric and protein intake (nPCR), from 1.28 ± 0.23 to 1.43 ± 0.24 g/kg at 6 months, and school attendance became regular. The only pre-pubertal child included showed catch-up growth.
Conclusions. Increasing dialysis frequency to daily sessions without shortening the durations of sessions excessively allowed us to overcome the free diet imposed on these paediatric, very uncompliant patients. This strategy led to a reduction in blood pressure and an improvement of left ventricular size and function, normalization of pre-dialytic plasma phosphorus and improvements in general well-being and dialysis acceptance. Long-term, however, this protocol is only acceptable for the children if associated with the potential of clinical recovery allowing inscription on the kidney transplantation waiting list.
Keywords: daily haemodialysis; growth rate; nutrition; on-line haemodiafiltration; ventricular function; ventricular hypertrophy
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Introduction |
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The aim of this pilot study was to demonstrate that daily dialysis with on-line haemodiafiltration (OL-HDF), the dialysis modality that offers the highest reduction of uraemia [6,7], should influence clinical outcome in children on dialysis, at least with respect to left ventricular hypertrophy or systolic function or both, similar to results demonstrated in adults [8,9].
For this study we included our pre-adolescent or adolescent chronic haemodialysed population, all of whom were excluded from a transplantation waiting list due to their cardiovascular status and their very limited compliance. All these patients had severe and long medical historiestheir motivation and their adherence to long dialysis sessions, diet recommendations and prescribed medications being less than optimal.
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Subject and methods |
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We included five children based on both their left ventricular hypertrophy and their impaired systolic function (Table 1). All had travel times to the hospital of <1 h (three of them <30 min). All had oligoanuric renal residual functions. Their mean age was 13.8 ± 3.2 years (range: 9 years 6 months16 years 1 month) and all were on standard OL-HDF (S-OL-HDF), 4 h, thrice weekly, during at least the preceding 6 months. They were switched to daily OL-HDF (D-OL-HDF), but without significant reduction of the length of the sessions, i.e. 3 h, six times weekly, in order to both achieve an increased dialysis dose and avoid the risks related to excessively high hourly ultrafiltration rates (usually limited to 1.5 ± 0.5% body weight/h [3]), especially in the presence of impaired cardiac function. The same haemodialysis configurations were used in the D-OL-DHF as were in use for the S-OL-HDFthe same machines (Fresenius 4008), the same dialysers (FX 6 polysulphone), identical blood (180 ± 50 ml/min) and dialysate flows (500 ml/min) and a pre-dilution mode with a reinfusion flow (limited to 200 ml/min) two-thirds of or equal to blood flow. All patients had native arteriovenous fistulas. Circulatory access was achieved using two 15-gauge needles whether on S-OL-HDF or on D-OL-HDF. Access problems (infection, thrombosis, stenosis) were noted. Diets changed from restricted (but not strictly followed) during S-OL-HDF to a free diet permitted during D-OL-HDF, the only limitation being the kalium diet intake due to its potential cardiovascular toxicity. CaCO3 was the phosphate binder prescribed (and, hopefully, taken by the children).
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Urea kinetic parameters and standard pre-dialysis blood analyses [i.e. haemoglobin, calcium, phosphorus, intact parathyroid hormone (iPTH), serum albumin, C-reactive protein (CRP) and homocysteine] were performed on samples collected monthly at a mid-week dialysis session.
At baseline and monthly thereafter, each patient was questioned about post-dialysis thirst and fatigue. Also recorded, in min, was post-dialytic recovery time, i.e. the time needed to allow standing up and walking after the end of a dialysis session. School attendance was noted, especially whether or not the patient had skipped the morning before or the afternoon after the session.
Pre-dialysis blood pressure was measured immediately before the session, with an automatic blood pressure monitor, and recorded as the systolic, diastolic and mean pressures. Dialysis intolerance during the session (hypotensive episodes, cramps) was recorded regularly. Weight gain was measured for each interdialytic period. Anthropometric measures were taken every 3 months: weight (kg), height (cm) and body mass index (BMI; kg/m2 body surface area).
Echocardiography was performed monthly by the same operator, on a mid-week non-dialysis day in S-OL-HDF and on a mid-week day before starting the dialysis on D-OL-HDF. The echocardiographic measurements included: interventricular septal thickness (IVS), posterior wall thickness at end diastole (PWT); ejection fraction (EF) and fractional shortening (FS), used as indices of left ventricular systolic function; diastolic function was assessed by measuring the early transmitral peak velocity (E) and the atrial transmitral peak blood velocity (A). Diastolic dysfunction was defined as an E/A ratio of less than 1.
The last 6 months on S-OL-HDF before switching the patients to D-OL-HDF were taken as the baseline period. Treatment was carried out at least until cardiovascular recovery, which allowed the child to be put on the transplantation waiting list and thereafter D-OL-HDF continued until transplantation. The results are expressed as arithmetic means ± SD. The Student's t-test was used for comparison of continuous quantitative variables. A value of P<0.05 was considered statistically significant.
All children and their parents were informed and both signed consent forms.
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Results |
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Daily dialysis was well tolerated by all children, without any pre-dialytic clinical symptoms over 54 patient-months of follow-up. Post-dialytic recovery time was 615 min at baseline on S-OL-HDF and thereafter disappeared. There was no (0 min) recovery time after conversion to D-OL-HDF, a stable condition that was achieved promptly (<1 month). The children's acceptance of the new daily schedule was difficult and needed several discussions and explanations during the first few weeks (14), until the disappearance of the pre- and post-dialysis fatigue, the immediate recovery from dialysis without a period of hangover and the perception of well-being throughout the week became apparent to them. This continuous sense of well-being associated with the absence of the stress induced by uncertainties related to weighing before dialysis sessions [How much interdialytic weight gain? How long a session (4 h or more)?] eventually brought about not just acceptance but a real demand for daily dialysis. Finally, adherence to the total regimen, dialysis and medication improved considerably in this pre-adolescent/adolescent group. No local infections, thromboses or problems of the vascular access occurred during the 54 patient-months of D-OL-HDF. School attendance was regular and the skipped school days before or after the dialysis session (the latter due to fatigue) disappeared, resulting in a real increase in school attendance. One adolescent, S.H. (Table 1), learned reading and writing after conversion to D-OL-HDF, due to enhanced school attendance, school work during the dialysis session and disappearance of variable feeling condition. Thirst did not change, but appetite increased in all children.
Increasing the number of sessions per week had a significant positive impact on the weekly dialysis dose (Table 2). The TACurea and the TADurea decreased and the nPCR increased on D-OL-HDF. Mean pre-dialysis haemoglobin levels increased after 12 months on D-OL-HDF, combined with a significant decrease in the erythropoietin doses required (Table 3). There was a significant decrease in pre-dialysis phosphataemia, despite the increase of nPCR on D-OL-HDF. At the same time, the dosage of phosphate binders (calcium carbonate) reduced by >50%. On D-OL-HDF, the calciumphosphorus product decreased significantly over time and so did pre-dialysis homocysteine levels. The mean pre-dialysis ß2-microglobulin levels slowly decreased on D-OL-HDF without significant changes for CRP.
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A considerable reduction of left ventricular hypertrophy assessed by IVS and PWT (Table 4) was observed when children were switched to D-OL-HDF. The left ventricular systolic function assessed by EF and FS improved (Table 4). We did not see any marked diastolic dysfunction in four of the five children at the inception of the study. Only one child had an early over atrial transmitral blood velocity (E/A = 0.87) at inclusion, which normalized after 6 months of D-OL-HDF. Reduction in blood pressure was achieved, although dry weight was increased by nearly 6 ± 1.2% at 6 months and 12.7 ± 2.1% at 12 months a mean dry weight increase of 10.7 ± 1.9% after 1 year on D-OL-HDF. An increase in the BMI was achieved, with a 2.8 ± 0.7 kg/m2 gain after 12 months of D-OL-HDF. The percentage of interdialytic weight gain did not change. In one child, R.M. (Table 1), catch-up growth occurred after 6 months on D-OL-HDF, despite a pre-pubertal status (Table 5)resulting in a gain of height score of 1.5 DS over 24 months (Figure 1).
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Discussion |
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Therefore, based on the reported data [1,2,8,15], we switched all five pre-adolescent/adolescent patients to the more physiological and effective dialysis schedule, daily dialysis, maintaining the dialysis modality that offers optimal blood purification, OL-HDF [4,5]. Our pilot clinical trial was able to confirm the previously described effects of daily [1,2] and high-dose dialysis [4] and, therefore, could be a recommendation for dialysis in very uncompliant patients, as adolescents with severe and long medical histories often are. We were also able to note restored child motivation and adherence to the therapy protocol.
D-OL-HDF was able to allow significant regression of the left ventricular hypertrophy and improvement of the left systolic ventricular function, with nearly a 50% increase in fractional shortening (Table 4). Since only one patient had marked diastolic dysfunction, which improved with time on D-OL-HDF, we could not identify any correlations with the other cardiac parameters in the study [16]. The results obtained for systolic function are in accord with recent data obtained in adult patients on daily nocturnal haemodialysis [1,2,9] and on D-OL-HDF [8,15]. These results are also in accord with the relationship between dialysis dose and cardiac function established in peritoneally dialysed children [17]. Better control of blood pressure was also achieved with D-OL-HDF, allowing four of five children to stop the antihypertensive medications they had been on. These major cardiovascular impacts were obtained promptly and were stable for all patients after 4 months of D-OL-HDF, allowing them access to the kidney transplantation waiting list. These major cardiovascular improvements were obtained prescribing a free diet that leads to regular nutrition and which replaced the variability of food intakes between free intake and fast days. Hyperhomocysteinaemia, an independent risk factor for cardiovascular disease [18], diminished on D-OL-HDF, probably due to the higher frequency of dialysis [8,5].
The tendency noted in our study of an increase in haemoglobin and a reduction of the erythropoietin dose appears inconsistent and is discussed in other reports [1,2,8,15].
The improvement in phosphate control on D-OL-HDF observed in our study has also been noted by most authors reporting on daily dialysis [1,2,8,15]. Likewise, the CaP product was reduced from >4.4 mmol/l to a lower level presumed to decrease the cardiovascular risk, at least in adults [4,5,13]. The observed lowered pre-dialysis phosphate levels could be the effect of both the dialysis schedule and the higher dialysis dose, but they could also be in part secondary to an improved anabolic condition, presumably resulting from D-OL-HDF [19]. In fact, dry weight and the BMI increased in our subjects; moreover, catch-up growth was achieved with D-OL-HDF in one anuric child with a severe medical history (Figure 1). Such a surge in growth rate is exceptional and, perhaps, only an irreproducible result; but there are some reports on the impact of paediatric dialysis dose [20,21] or on the total dialysis management [22] and observed positive growth rates without use of growth hormone therapy.
These excellent clinical results with D-OL-HDF could be secondary both to the dialysis schedule (daily being more physiological with less fluctuations in volume, solutes and electrolytes) and to the increased dialysis dose [20] impacting not only on urea clearance enhancement, which is considered of limited clinical impact [23], but also on other uraemic toxins due to the use of OL-HDF, since the dialysis modality offers higher uraemic toxin removal [68]. All these results, however, also could be influenced by the improvement of child compliance with the therapy, induced by the dialysis schedule and linked with the hope of access to the transplantation list, a major motivating factor.
Finally, D-OL-HDF offers a schedule with optimal comfort during dialysis and optimal recovery immediately thereafter, allowing quite a normal life during off-dialysis periods [1,2,8,15]. The gradual discovery by our adolescent patients, after <1 month on D-OL-HDF, of the disappearance of the usual tidal fluctuations resulting from the thrice weekly strategy helped overcome the initial perception of something forced upon them, daily dialysis with a too-frequent schedule, and lead to real adherence to daily dialysis. The fast day before dialysis and the fatigue before and after the sessions disappeared, as did the hangover and the delay of recovery. The thrice weekly dialytic strategy had generated adolescent opposition and, therefore, non-compliance by, for example, the prolonged dialysis session being considered as a sanction against the excess interdialytic weight gain. Thus, with the new schedule, child opposition was suppressed and child motivation could be restored. The daily dialysis frequency allowed a fixed dialysis duration, giving the adolescent the ability to programme free time, even in the evenings after a dialysis session. School attendance was complete on all of the off-dialysis days and even on the half days before or after the dialysis sessions. The absence of problems with vascular accesses and, even more, the improved healing process of the puncture sites, combined with the patients sense of well-being (no fatigue, no tidal form and no half fast days before the sessions), convinced our entire team that daily dialysis freed these children from the detrimental impacts of thrice weekly conventional dialysis strategy on physical condition and psychological form. Daily treatment in dialysis centres might be a good therapeutic option for selected paediatric patients, especially if their travel time to the dialysis centre is acceptable.
Nevertheless, the acceptance of a daily dialysis schedule by team members and medical and paramedical staff was stepwise. Daily dialysis, with long dialysis sessions, as in our study, initially appears very difficult to accept; therefore, it may lead to the abandonment of the approach. Firstly, acceptance could be facilitated by the scheduling of the procedure. Dialysis was performed either in the morning or the late afternoon, after consulting with the schools home teachers, and preferably during the half days away from the classroom, e.g. during half days allocated to music or sport. All children in this study had short travel times to the dialysis centre (<1 h for all and <30 min for most). Altogether, travel, dialysis and meal times added up to <5 h daily, usually 4.5 h. The children were driven from home or school by a taxi to the dialysis centre; a meal was offered during the first 30 min of the session; one teacher for each child conducted a private course based on the child's needs and in coordination with the home teacher and class (via fax and Internet connections). Thus, each dialysis session offered a 2 h private course or tutorial for doing school work. Due to the optimal dialysis tolerance, these intradialysis school activities occurred regularly. Secondly, acceptance also resulted from the patients sense of well-being and their freedom from symptoms before and after dialysis (there, especially, was no post-dialytic fatigue), allowing them full activity during all their off-dialysis time and regular school attendance before or after dialysis sessions. This is a real change compared with the usual thrice weekly protocol, where the children were themselves limiting their activities before a dialysis session, and because the permitted interdialytic weight gain had been achieved, they had been resorting to pre-dialysis fasting. They had also limited their activities following dialysis sessions, because of fatigue after the 45 h session, which with travel time in fact amounted to 5.5 or 6 h, taking up more than a morning or encroaching upon the evening. In practice, school attendance after a long morning session had been nil and evening life was reduced after a long afternoon session. After a few weeks of daily dialysis, the children acclaimed their new really free living time. Thirdly, acceptance of daily dialysis could be bolstered with a new goal: that is, to be in a clinical condition to be eligible for the kidney transplantation waiting list. Finally, relatively longer sessions of daily dialysis (i.e. 3 h) were necessary because free diets were allowed and we had to consider the risks of overly elevated hourly ultrafiltration rates (usually limited to 1.5 ± 0.5% body weight/h [3]), especially in children with impaired cardiac function. The duration of the session, of course, could, and would, be adjusted to individual needs.
All the data currently available [3,4,17,20,21], even in children, support the beneficial impacts both of an increased total weekly dialysis duration at the best achieved through daily scheduling, which is considered more physiological than intermittent schedules, and of an increased dialysis dose, optimally increasing not only small solute clearance, which is a too-limited parameter of adequacy [23]. The case for more dialysis dose should improve clinical outcome [4,5,21]. It is our opinion that daily dialysis could be the optimal dialysis in at-risk patients, especially if done for a limited time and considered a pre-transplantation strategy.
However, in-centre, long, daily dialysis is, without doubt, difficult to justify if used only for end-of-life management. In such cases, with no possibilities of transplantation and no alternative to dialysis care, one or all of home dialysis [15], in-centre, short, daily dialysis [8] or long sessions thrice weekly [4] should be discussed and offered to patients, as complementary methods of life support.
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Acknowledgments |
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References |
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