Daily dialysis: is this a reasonable option for the new millennium?

The best way to predict the future is to create it. PETER F. DRUCKER (Austrian-born American economist)

Zbylut J. Twardowski

Division of Nephrology, Department of Medicine, University of Missouri, Columbia, Missouri

Keywords: daily dialysis; dialysis adequacy; hemeral haemodialysis; home haemodialysis; nocturnal haemodialysis; quotidian haemodialysis

Introduction

Chronic haemodialysis was introduced by Scribner and his collaborators in 1960 [1]. Initially two patients were dialysed for 24–76 h every 4–21 days on the Skeggs–Leonards (parallel plate) dialyser [2], but it became clear that the patients developed uraemic symptoms before the next dialysis, so dialysis frequency was increased to twice weekly [3]. Ultimately the frequency of haemodialysis was established as thrice weekly at the end of 1960s [4]. With the low-efficiency dialysers, the time of dialysis remained relatively long, up to 8 h. Such a schedule of 8 h, three times weekly dialysis continues to be practised in some centres, with excellent results [5].

Early attempts of short, frequent haemodialysis

In the late 1960s the hollow-fibre dialyser was designed [6,7], the efficiency of dialysis could be markedly increased and it became fashionable to increase efficiency and shorten dialysis time. However, short, thrice-weekly dialysis was insufficient in patients who had lost residual renal function. The first attempt of more frequent dialysis was made in Los Angeles, California, in 1967 [8]. Several patients doing poorly on three times weekly dialyses were switched to five times weekly short dialysis sessions. In all of them uraemic symptoms disappeared, hypertension became manageable; haematocrit, albumin, and dry body weight increased. The programme was discontinued after 3 years because the technology for frequent dialysis was not developed at that time [9]. The next attempt of five times weekly, short dialysis was made in Bologna, Italy [10]. Again, significant clinical improvements were observed due to lower osmotic fluctuations, and again, the programme was discontinued because of lack of appropriate technology.

In 1975 another attempt to implement daily, short dialysis was made at Maimonides Hospital in Brooklyn, New York. In 11 patients, many beneficial effects were noted. Most significantly the patients reported disappearance of all uraemic symptoms and post-dialysis ‘washout’ and fatigue. An observation was made that fistula function was better maintained with daily dialysis. This was attributed to the absence of hypotensive episodes and improvement in immune defence [11]. The programme was abandoned, due to lack of technology and appropriate reimbursement.

Frequency/length of haemodialysis and clinical/laboratory results

A systematic study of the influences of dialysis frequency and duration was performed in the mid 1970s [1214]. Fourteen patients, dialysed on UF-140 coil dialysers with blood flow of 200 ml/min and dialysate flow of 500 ml/min, participated in an experiment. The patients were dialysed twice weekly for 12 h, thrice weekly for 8 h, or four times weekly for 6 h. In six patients the dialysis time was increased by 17.5% (from 6 to 7 h or from 8 to 9 or 10 h). In eight patients, the weekly frequency of dialysis was increased from twice to thrice or thrice to four times, without changing weekly dialysis time. The mean follow-up time was approximately 6 months. Both groups showed improvement in many parameters, but the improvement was almost always greater in the patients who were treated more frequently. With increased frequency by one per week, haematocrit increased by 4%, albumin by 0.45 g/dl, nerve conduction velocity by 6.1%. Increased haematocrit with more frequent dialysis was particularly noteworthy, because blood loss with a single dialysis was approximately 20 ml. Thus, either red blood cell production was markedly increased or red blood cell destruction was noticeably decreased with more frequent dialysis. Increased duration improved parameters only moderately: haematocrit by 1% and albumin by 0.3 g/dl, but nerve conduction velocity did not change significantly. Both increased dialysis time and frequency significantly improved blood pressure control. Systolic blood pressure dropped by 14 mmHg, and diastolic by 6 mmHg with increased frequency and with increased duration by 14 and 7 mmHg systolic and diastolic respectively. Ultimately, antihypertensive medications could be discontinued. A seemingly paradoxical observation was that more frequent dialyses were associated with improvement in the fistula condition. This phenomenon was attributed to improvement in uraemic thrombopathy that decreased the tendency to haematoma formation at the puncture sites.

Long-term programmes of short, daily haemodialysis

The longest-operating daily programme with short haemodialysis sessions was established in Perugia, Italy in 1982 [15]. Observations in patients on daily dialysis confirmed all previous observations and added new ones. Improvements in haematological parameters, blood-pressure control, nutrition, and quality of life were again noted. Moreover, improvements were noted in myocardial function and morphology, hormonal disturbances, and sexual life [16].

Yet another Italian programme, in Catanzaro, again reported almost identical observations: improvements in quality of life, hypertension, myocardial function, normalization of the levels of hormones, return of normal menstrual cycles in women, and good sexual function in men. One woman had a successful pregnancy while on daily dialysis [17].

Recent programmes of short, daytime and long, nightly frequent haemodialysis

In recent years several groups in Canada, Belgium, the Netherlands, France, Finland, Brazil, Germany, and several centres in the United States established quotidian dialysis programmes, either short, performed during the daytime or long, performed during the night* [1823]. All reports confirm beneficial effects of quotidian haemodialysis on blood pressure control, haematocrit, nutrition, mental health, energy, social functioning, physical activity, and vitality. A combined report on 72 patients from nine centres, performing hemeral haemodialysis, confirmed excellent influence of daily dialysis on haematocrit, albumin, blood pressure control, patient survival, technique survival, and blood access function [24]. Moreover, use of drugs, morbidity, and need of hospitalizations markedly decreased. Therefore, despite of higher cost of dialyses themselves, the global cost of treatment of patients with ESRD is lower [21]; however, the cost of dialysis alone is higher and is not reimbursed to dialysis providers.

The only comparative study by Dr Robert M. Lindsay in London, Ontario, Canada, showed no clinical advantage of either nocturnal or hemeral haemodialysis [25], despite the efficiency of nocturnal haemodialysis being markedly higher than hemeral, even to the degree that patients require phosphate supplementation instead of phosphate binders. Other deficiency states have not been described, but prophylactically the patients receive higher vitamin supplementation [23].

Impediments to the widespread use of quotidian haemodialysis

Early attempts of quotidian haemodialysis failed because of lack of suitable equipment. Today technology is better, but still not prepared for quotidian haemodialysis. For quotidian home haemodialysis, the machine must be easy to operate and decrease the total time spent on dialysis-related tasks. Besides dialysis, these include the set-up, priming, tear down, and cleaning of the dialyser and equipment. In addition, the cost of haemodialysis should not increase significantly.

Machine for quotidian, home haemodialysis

In the 1980s, I came to the conclusion that quotidian home haemodialysis could only be practical if a new machine were built that would reduce the time required of the patient and the money required of the provider [26]. Three components seem crucial for a small device: a built-in water-treatment system; a simple, positive-pressure, single pass, batch dialysate system; and a reusable extracorporeal circuit, automatically cleaned and disinfected daily. The bicarbonate-based dialysis solution, prepared mostly from dry chemicals (dextrose, sodium chloride, sodium bicarbonate) and low-volume concentrates (calcium chloride, magnesium chloride, potassium chloride, and organic acid) mixed with treated water automatically in a small batch tank seem simple and economical. Elimination of a proportioning system significantly simplifies machine design and reduces its cost. Further simplification and cost reduction is achieved by the use of positive-pressure ultrafiltration that eliminates the need for a de-aeration pump. Use of dry chemicals instead of concentrates lowers transportation costs, considerably decreases the need for storage space, and lessens the burden on patients. The reuse of the dialyser and the extracorporeal blood circuit would keep treatment cost relatively low [27,28]. The blood compartment of the dialyser is filled with sterile dialysate, which further reduces transportation costs and simplifies the procedure [29]. It took several years to found a company (Aksys, Ltd, Lincolnshire, Illinois, USA) and build a first version of the machine, called the personal haemodialysis system (PHD) [30].

Recently the PHD obtained an Investigational Device Exemption (IDE) status from the Food and Drug Administration and has been tested in 25 patients [31]. In November 2000 the study was completed and a report is being compiled to be submitted to the FDA. The patients performed more that 2100 dialysis sessions on the PHD, including more than 1600 at home. The machine proved to be safe, dialysers and lines were cleaned well, and there was no significant decrease in dialyser clearances with consecutive uses. Subjectively the patients experienced typical benefits of quotidian dialysis: minimal interdialytic and intradialytic symptoms, improved mental health, energy, social functioning, physical activity, and vitality; blood pressure was well controlled with decreased use of antihypertensive drugs, and haematocrit was well maintained with decreased use of erythropoietin, in spite of substantial blood loss for laboratory tests related to the study.

Blood access in quotidian haemodialysis

Frequent dialyses are sometimes perceived as a risk factor for blood access malfunction and its decreased longevity, because of increased frequency of access punctures. A review of the literature [32] indicates that the failure rates and overall fistula survival appear to be better with more frequent dialyses than with the routine dialysis frequency. The reason for this phenomenon it is not clear.

Conclusions

More frequent than routine thrice-weekly dialysis programmes are developing rapidly in many centres in the world. Most centres perform hemeral, relatively short sessions, but several perform nocturnal, long sessions. More frequent dialyses provide excellent clinical results, without detrimental effects on the blood access. An appropriate technology is developing to facilitate the widespread use of quotidian haemodialysis. In the United States, an additional stimulus for this therapy would come from a change of the reimbursement method; instead of paying separately for dialysis, drugs, and hospitalizations, the payment should be for the total patient care.

So my answer to the question posed by the editors of this journal is: Yes, daily (quotidian) dialysis is a reasonable option for the new millennium.

Notes

Correspondence and offprint requests to: Zbylut J. Twardowski MD, Dialysis Clinic, Inc, 3300 LeMone Industrial Blvd, Columbia, MO 65201, USA. Back

In English, ‘daily’ has two meanings: 1. Of or occurring during the day. 2. Happening or done every day. Therefore, to avoid such awkward expressions like ‘daily nocturnal’ or ‘daily nightly’, I propose to introduce a new terminology for dialysis performed every day or every night. Every day is called quotidian (from Latin, quotidie, each day); that performed during the daytime is called hemeral (from Greek hemera, day-time as opposed to night-time) and nightly is called nocturnal (from Latin nox, night). Back

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