Bionic Kidney

• Bionic kidney
• Chronic uremia
• Dialysis
• Transplantation

Introduction

The present standing of Renal Replacement Therapy ((RRT)) is well‐‐known: it heads the ranking in Artificial Organ Replacement for the quality and quantity of results; it affords excellent survival both in dialysis and in transplantation; but it is stil inadequate in fulfilling all the other original expectations ((rehabilitation, cost//benefit, quality of life)). It has generated first and second class patients in transplantation; and dramatic economic problems in dialysis, the cost//benefit being doubly disappointing. This is not a surprise, after all if one reflects on what has been done in 20 years to really solve the “core” of the matter i.e.: to have a device functioning as a kidney in dialysis; and to have specific and not specific immunosuppressants in transplantation. The answer is: virtually nothing; only recicling of data differing in form, but not in content.

What is really needed in RRT is a radical rethinking taking into proper consideration the disappointing truth of the long‐‐term patient's reality; the three spearheads of any such rethinking are: Bioartificial Kidney in dialysis; specific immonosuppressants in transplantation; gene therapy aiming at preventing organ damage or its progression to failure and thus will make dialysis and transplantation no longer necessary.

My report, today, only deals with the first point, that is bioartificial organ, and, in particular, the role that bionics may have within this frame.

The conceptual evolution of replacement from artificial to bioartificialtherqapy is an old idea, but unfortunately never realized in clinical terms. It includes all the procedures so far proposed with a view to biologizing the device to make the so‐‐called “Artificial Kidney more humanized and less unphysiological”, thus improving the clinical results. Several years ago, an experimental proposal, the Hybrid Organ ((engineered cells on a hemofilter)) was proposed by Galletti. In strictly biological terms this is a misnomer. Hybrid would actually apply to an organ deriving from the mingling of two genetically different biological systems. Today, however, the name is accepted by extension: so that Hybrid Organ comes to mean a mixed organ with cells superimposed on the filtering membrane, which is the basis of the Bioartificial Kidney, a project that received little attention until a few years ago. Various directions have been proposed, all based on two principal assumptions:

1. expanding stem or progenitor renal cells in tissue culture so as to perform differentiate functional tasks;

2. placing the cells on the hemofilter capillary.

Among the various problems still to be solved, one seems of particular interest i.e. the correlation between the cells and their polymeric supporting substrate. Complex molecular forces are involved in this cellular traction, including cytoskeleton, actine elements, miosine‐‐motors and other molecules, which further postpone the clinical feasibility of the Bioartificial Kidney. No clinical studies, as far as we know, have been successfully carried out.

And so we come, finally, to the evolution of Bionics in RRT, which is today's most advanced biotechnological renal project aimed at activating all functions of normal human kidney.

Bionics is a newly emerging science, dealing with functional analogies between living organisms and certain devices ((wether electronic or mechanical)). It can be seen as Organs, Programmes and Trends, and may be used in offsetting most of the negative sides to both transplantation and dialysis.

On this matter we have been working for many years now ((Table 1)). On various occasions we have reported on the significance of the bionic approach to RRT from a number of angles ((clinical, biological, theoretical, philosophical, etc.)) all essentially based on the two pillars of Bionic Science:

1. making the patient more biologically suitable for RRT ((dialysis and//or transplantation)); and

2. making RRT ((dialysis and//or transplantation)) more biologically suitable for the patient.

Table 1. Bionics in renal replacement therapy ((V. Bonomini, University of Bologna))

“Varieties of Bionic Support in Renal Transplantation” ((Montreal, 1991))

“Bionics in Renal Replacement Therapy” ((Yokohama, 1992))

“The Bionic Evolution of Renal Replacement Therapy” ((Baltimore, 1992))

“Bionic Support in Renal Replacement Therapy” ((Sorrento, 1992))

“The Bionic Kidney” ((New Orleans, 1993))

“Replacement Science” ((Boston, 1994))

“Bionics: Philosophy of the Approach” ((Barcelona, 1998))

“Bionic Kidney” ((Roma, 2000))

The basic assumptions if bionics in dialysis are:

1. combining dialysis technology with biological strategies to improve the functional performance;

2. connecting biology and technology by electronic feed‐‐back sensors triggered by on‐‐line patient clinical requirements;

3. modulating biomaterial reactivity to offset the patient's biological trade‐‐off.

These goals can be achieved by bionics‐‐inspired lines of dialysis biotechnology:

• Clinically Computerized Dialysis

• Interactive Biomaterials

• Permselective Membranes

• Specific Sorbents

• Biosensors for On‐‐Line Clinical Self‐‐Modulation

• Bioreactors for On‐‐Line Biological Monitoring

• Encapsulated Cells

• Implantable Bionic Kidney

The institute of Nephrology of the University of Bologna, in collaboration with the Department of Electronics and Applied Biology, has been working for many years now on a model of Bionic Kidney designed to possess all renal functions. It consists of miniaturized filters, de‐‐antigenized membranes, genetically codified cells, biological sensors and computer modelling. It is hard to estimate the time needed to implement the model shown here in diagram‐‐form, in view of the complexity of the various phases it requires:

1. defining the depurative component ((filter and solute));

2. defining the biological component ((progenitor renal cells));

3. evaluating the two components separately;

4. assessing the functional interaction between them ((specific bio‐‐sensors)).

We can say, at this stage, that the technological components ((micro‐‐filters and micro‐‐reactors)) are contained in micro‐‐containers; that the biological component ((in the future: renal cells genetically coded to functional tasks)) is made up of high biological turnover cells ((lymphocites)); and that computerized in vitro checks and in vivo application of individual parts to animals seem to confirm the validity of the groundwork to the Bionic Project in progress, with its aim of replacing all renal functions.

Set into the extra corporeal circulation, the Bionic Kidney contains all the requisites for complete rehabilitation from uremia. As a futuristic mini‐‐device implanted in the body it should be a reliable support to transplantation performance, considering the scarcity of kidney donors and the long‐‐term results, which are not so spectacular as believed.

While the Bionic Kidney is still a matter for the future, Extracorporeal Bionic Programmes have already mad progress, and new trends are being implemented in two main directions:

1. “Humanized” devices;

2. Interactive bio‐‐materials.

Sophisticated devices and programmes are already being used in which direct patient//machine feed‐‐back permits on‐‐line adjustment of alterations mainly related to the kidney excretory loss ((urea volume, electrolytes, buffer changes)).

A number of experiments today are working on “biologizing” Bio‐‐material by various techniques and there is every reason to expect that this resource will soon also be available in dialysis. Membranes may be “enriched” withy active molecules, enzymes, bioproducts and codified cells. Via specific biosensors inserted in the circuit the patient will be able to call for the activated biomaterials he needs, directly and “on‐‐line”, and so restoring his bio‐‐clinical needs.

These are typical examples of Humanized Extracorporeal Bionic Dialysis.

In conclusion, the spirit of RRT is permitting life, but the quality of the technology will decide the quality of that life.

If RRT is to have a clinically and socially justifiable future, considerable creative effort is needed with research aimed at improving both dialysis and transplantation. The new envisaged devices or programmes should be optimized with a view to:

1. enhancing the quality of life in RRT;

2. improving candidacy for transplantation;

3. creating it an alternative to transplantation itself.

Bionics seems one possible answer to these requirements but, wether it will be backed appropriately and so have a large scale application, only time will tell. The results of our experience are hardly encouraging: research initiated 12 years ago; a programme was presented 8 years ago; a patent has been in our hands for the last 6 years; clinical application today: zero. And this “zero” goes for bionic as much as for other models of present Bio‐‐Medicine. This field has seen no adequate clinical trials on use. Nevertheless we continue to hope and dream. However, for dreams to become reality, science has to find a more enlightened response in the context of all the worlds involved in the “Health problem” ((political, social, economic, ethical and private)). Only then, can “Health” become a resource and a commitment for the whole community. This ngoes for science in general, and for bionics in RRT in particular.

This is the real challenge for the new millennium.

Uncited References

Bonomini et al., [1992].

Bonomini et al., [1993a].

Bonomini et al., [1993b].

Bonomini et al., [1994].