ARTIFICIAL KIDNEY — the device for removal from an organism of toxic products of exchange and exogenous poisons, and also for regulation of an electrolytic water balance and acid-base equilibrium by means of dialysis and ultrafiltration of blood.
Nominative temporarily replaces functions of kidneys on maintenance homeostasis (see), but does not model renal processes (glomerular filtering, a canalicular reabsorption and secretion, etc.) and incretory function.
Hemodialysis (see) — release of blood from crystalloids thanks to selective diffusion of substances through a semipermeable membrane. In Nominative this membrane separates sterile kroveprovodyashchy system from the unsterile system which is carrying out the dialyzing solution. Depending on permeability of a membrane, its area, a design of the device, temperature of solution, a difference of concentration of substances on both sides of a membrane, the size and a form of their molecules, etc. dialysis of different substances in various types of Nominative happens unequally quickly.
Ultrafiltration (see) — removal from an organism of water owing to a difference of hydrostatic and osmotic pressure on both sides of a semipermeable membrane. The pressure gradient, necessary for ultrafiltration, is reached in Nominative of hl. obr. at the expense of positive pressure in kroveprovodyashchy system and negative pressure in system of the dialyzing solution. Process of elimination of water can be strengthened, having increased the osmotic pressure of the dialyzing solution due to addition of osmotically active agents (glucose, Mannitolum).
Works on creation of Nominative began with J. J. Abel's research and sotr. (1913) which developed the first prototype of the equipment for a hemodialysis called «an artificial kidney». The device represented a number of the tubes made of a semipermeable membrane (collodion), placed in the glass cylinder and united in the general collector with the beginning and the end of the cylinder. The cylinder was filled fiziol. solution of sodium chloride (the dialyzing solution). The device was attached to blood vessels of an animal, providing blood circulation through it at the expense of the ABP. For prevention of a blood coagulation entered anticoagulant hirudine. The conducted researches showed that it is possible to delete products of metabolism and toxicants of an exogenous origin from blood. These researches had great scientific value, however the equipment and a technique of its use were very imperfect.
The Nekheles (H. Necheles, 1923) for the first time used the device created by it, in Krom for removal of products of proteinaceous metabolism at dogs with experimental uraemia as a semipermeable membrane the peritoneum was used. The first use of Nominative for the person was carried out by Haas (G. Haas, 1925 — 1927). The device created by it was used for treatment of uraemic intoxication. Despite the lack of explicit the wedge, effect, was succeeded to note removal with solution of nek-ry quantity of metabolites of a nitrogen metabolism. In Haas's works for the first time for advance of blood via the device the special pump was used. During a hemodialysis Lim (R. K. of S. Lim) and Nekheles (1926) for the first time applied to creation of artificial hemophilia heparin (see) instead of earlier toxic and hardly standardized hirudine used.
Serious difficulty in creation of Nominative long time remained lack of the semipermeable membrane meeting the requirements of a hemodialysis. Numerous options of such membranes (a collodion, a swimming bubble of fishes, a peritoneum of a calf, etc.) owing to a non-standard and low mechanical strength were unacceptable for wide use. This task was solved by Talkhaymer (W. Thalhimer, 1938) who for the first time offered and who tested cellophane for this purpose.
The accumulated experience, especially use of heparin and cellophane, created necessary premises for development of the first suitable for wide a wedge, uses of version of the device of Nominative created in 1943 by the doctor U. Kolff in the commonwealth with the engineer Burke (N. of Berk). Soon N. Alvall (1946) it was created by Nominative, edges along with dialysis could provide also ultrafiltration. In the next years treatment by means of Nominative began to be applied in more and more wide scales. The large number of the models differing on a design of a number of the main nodes was created.
In our country creation of the device of Nominative was begun in 1955 at the initiative of the academician V. V. Larin. For the first time the device of Nominative was used to treatment of patients with a renal failure at the beginning of 1958 by A. Ya. Pytel, N. A. Lopatkin, and the first Soviet device created by group of doctors and engineers (M. G. Ananyev, Yu. G. Kozlov, E. B. Gorbovitsky, etc.) — in 1960
All devices of Nominative, despite a variety of constructive decisions, have the identical schematic diagram and consist of the following basic elements: 1) dialyzer; 2) the perfused device for advance of blood via the device; 3) the device for preparation and giving in the dialyzer of the dialyzing solution; 4) the devices controlling and regulating the key technical and medical parameters of a hemodialysis (monitor).
Dialyzer (haemo dialyzer). The considerable number of various versions of the dialyzers differing on a design, the used materials and membranes is developed and is used (tsvetn. fig. 1 — 4). All of them can be divided into basic groups: dialyzers in the form of drums (mobile and motionless); in the form of coils; dialyzers of lamellar type; capillary.
The first Nominative, developed by U. Kolff, had the dialyzer in the form of the rotating drum on which spiralno in one layer the cellophane tube was reeled up. Blood in a tube moved by the principle of the screw of Archimedes. Though Kolff's dialyzer and dialyzers with a motionless drum (Alvall, Battezatti, Meller) because of their bulkiness, complexity of assembly, large volume of primary filling and other shortcomings are practically not used, they were a basis for the subsequent developments.
The dialyzers of bobbin type developed by U. Kolff and Uochinger (V. of Watchinger) in 1956, represent the tube from a semipermeable membrane which is reeled up in several layers on a firm basis of a cylindrical form. For prevention of increase in volume of a tube at circulation of blood through it it from two parties is limited to the plastic grids which are not complicating at the same time contact between a membrane and the dialyzing solution.
Dialyzers of lamellar type are for the first time developed by Skeggs and Leonards (L. T. Skeggs, J. R. Leonards, 1948). In these dialyzers as basic elements of a design serve sheets of a semipermeable membrane which are fixed between the plates from polymer supplied with longitudinal flutes by means of which during the filling of the dialyzer with blood its directed flow forms. Outside the semipermeable membrane is washed by the dialyzing solution. Combining necessary number of the structural elements mentioned above, it is possible to receive dialyzers with the set working area. The models Kiil, Gambro, Rhone — Poulenc, an also the dialyzers which are used in domestic devices of Nominative are among lamellar dialyzers (AIP-140, Diakhron-80, SGD-6, Diatsentr-1, etc.).
Broad application is found by so-called capillary dialyzers. Their basis are thin-walled (11 — 30 microns) capillaries from a semipermeable membrane with an internal diameter about 200 — 260 microns. United in the bunches containing thousands of such tubes they are located in cylindrical cases from transparent plastic. At the beginning and the end of such cylinder all intervals between capillaries are pressurized by special structure, separating thus kroveprovodyashchy system from a circulating system of the dialyzing solution arriving via side unions of the cylinder.
The semipermeable membranes used in Nominative are the most important functional element of the device. Efficiency of Nominative and its safety for the patient generally depend on their features. There are following main requirements to a membrane, it shall:
1) not to have adverse effect on blood and not to allocate at contact with it of toxic products (not less than 95% of all foreign surface are the share of a semipermeable membrane, about a cut blood during the passing through Nominative adjoins); 2) to provide effective removal of metabolites and toxic products of an exogenous origin; 3) to provide the necessary speed of ultrafiltration; 4) not to pass squirrels; 5) to have the high durability preventing a rupture of a membrane at mechanical loadings and a temperature schedule.
The majority of the applied membranes make of cellulose derivatives (cellophane, kuprofan, nefrofan, etc.). Pore sizes in these membranes make 1,5 — 2,5 nanometers, thickness of membranes fluctuates from 10 to 20 microns. Membranes significantly differ on the dialyzing activity and ability to ultrafiltration that allows to carry out their rational selection during the carrying out a hemodialysis.
A certain place in development of an uraemic syndrome is allocated to so-called middlemolecular metabolites which chemical nature is not deciphered. In this regard the membranes which are characterized by much higher rates of clarification of middlemolecular substances in comparison with usual membranes for a hemodialysis were developed (on a basis polyacryle nitrile and some other polymers). These membranes have several times bigger ultrafiltrational activity that allows to remove at a hemodialysis bigger amount of liquid (to several liters an hour), and also to use them in special ultrafiltration organisms (for example, for sharp reduction of volume of ascitic liquid before its reinfusion). However in most cases excessively high ultrafiltrational activity of these membranes creates the difficulties connected with need carefully to control fluid losses at a hemodialysis and to timely offset its excess losses. The researches directed to creation of membranes which would have the high clearing ability in relation to middlemolecular metabolites are conducted and at the same time would keep the ultrafiltrational activity close to activity of membranes from a kuprofan, etc. At the same time membranes with high rates of ultrafiltration can be irreplaceable for the developed new type of the device of Nominative, action to-rogo is based on the principle of a diafiltration.
Dialyzers are issued with various area of a dialysis surface (from 0,24 to 2,5 sq.m) according to features of their use (e.g., with a small area for pediatric practice etc.). Depending on it change the clearing and ultrafiltrational power, and also other parameters (e.g., the volume of primary filling). The most important parameters characterizing various dialyzers — the sizes, a method of sterilization, time of preparation for work, volume of primary filling, residual volume, clearance on low-molecular substances, clearance on middlemolecular substances, ultrafiltration, internal resistance, frequency of breaks of a membrane, a possibility of re-using.
Dialyzers as for single, and repeated use are issued. All dialyzers of capillary and bobbin types and a number of models of lamellar dialyzers — disposable. These dialyzers are issued completely collected, sterilized and ready to immediate use. At respect for certain precautions some of them can be reused. According to the European association of dialysis and transplantation (1975), during the carrying out a hemodialysis in a hospital use dialyzers disposable, at treatment in house conditions both that and other type more often — approximately with an equal frequency.
The main efficiency factors of Nominative are clearance and dializans which show what volume of the dialyzed liquid completely is cleared of this substance for a unit of time (min.) at the chosen speed of perfusion. Clearance and dializans are calculated by Wolf's formula (A. Wolf, 1952):
C = (A-R) *a/A; D = (A-R) *a / (A - U),
where With — clearance (ml/min.); D — dializans (ml/min.); And — concentration of substance on an entrance to the dialyzer; R — concentration of substance on escaping of the dialyzer; U — concentration of substance in the dialyzing solution; and — the speed of the dialyzed liquid (ml/min).
The clearance characterizes the device at continuous updating of solution, in Krom on an entrance to the dialyzer there is no studied substance. Dializans characterizes the device as well at recirculation of the dialyzing solution when in the course of dialysis in it concentration of the studied substance increases and the clearance respectively falls.
For definition of efficiency of Nominative usually investigate clearance of urea and creatinine. Solutions of urea (3 g/l) and solution of creatinine (0,2 g/l) are applied to this purpose. On one research it is necessary apprx. 20 l of solution. As the dialyzing solution the diart. water is used. Temperature of both solutions — 37 °. The research is conducted during the passing of the dialyzed solution via the dialyzer with a speed from 50 to 250 ml/min. Samples are taken after the dialyzer worked in stable conditions apprx. 15 min.
Perfused device. Connection of the patient with the device can be carried out in various ways. In acute cases when there is a hope for bystry recovery of function of kidneys, quite often use the special catheters entered into large veins. At hron, a renal failure or at the long course of an acute renal failure most often use arteriovenous shunts or an arteriovenous fistula (see. Hemodialysis ). During the use of a method of catheterization and during the work with the help of an arteriovenous fistula it is necessary to use special perfused pumps whereas the arteriovenous shunt often provides a blood stream in the device without pump. There are various types of pumps: membrane, roller, sigma pumps. More often roller pumps find application. Sometimes for assessment of intensity of perfusion use also flowmeters by birth (Doppler, electromagnetic, ball, etc.). For introduction to blood of various medicinal substances, in particular heparin and a protaminsulfat, usually use two types of pumps: syringe pumps less often roller.
The device for preparation and giving of a dialysis fluid. Experience of use of Nominative showed that the dialyzing solution shall contain cations of sodium, potassium, calcium, magnesium and anions of acetate (or bicarbonate, a lactate) and chlorine. At the expressed extravasated overhydratation sometimes add this or that amount of glucose to solution, but it is no more than 3000 mg of % as higher concentration can lead to complications (a hyperglycemia, spasms, etc.).
The dialyzing solution can change in the known limits, napr, depending on a wedge, requirements, and also from composition of the water used for preparation of solution. Content of potassium is exposed to the greatest variations. The quantity entered into solution of calcium and magnesium can depend on their content in water. In a number of places mains water contains excess of salts of calcium, magnesium and other salts, and then pre-treatment of water is required for what use several methods. Distillation allows to receive well treated water, but this way is expensive therefore use demineralization of water by means of ion-exchange resins more often.
In simpler option when it is required to remove only calcium and magnesium, apply water softening that is reached by means of only cation exchangers. More and more widely the method of preparation of water by means of a reverse osmosis began to enter practice of a hemodialysis. For power tool cleaning of water from a rust, organic suspensions and other pollution use various systems of filtering.
Prepare the dialyzing solution in two ways. In a number of devices of Nominative add dry salts or their concentrated solutions to a certain water volume to receive the necessary concentration after their dissolution. Besides, apply an automatic way of continuous preparation of the dialyzing solution from a so-called concentrate and water. In a concentrate the content of all salts making it is 30 — 35 times higher, than in the dialyzing solution. Therefore one part of a concentrate is parted with 34 parts of water that is carried out by means of special devices — dosers.
The dialyzing solution in Nominative is used in three ways. 1. Recirculation. The ready dialyzing solution is in one capacity and, having passed the dialyzer, again is returned to the same capacity. As concentration of the products of exchange which are washed away from an organism in solution constantly raises, required periodic replacement with its fresh solution. Frequency of change is defined by the capacity of a tank and speed of accumulation in solution of slags. 2. System «on discharge». The dialyzing solution once passes through the dialyzer and merges in the sewerage.
There are systems in which the fulfilled solution is subjected by regenerations then it comes to circulation again. Actually here the principle of recirculation is used, but the nature of dialysis approaches the system «on discharge». 3. Combination of recirculation and system «on discharge». Via the dialyzer with high speed the amount of the dialyzing solution proceeds a nek-swarm, but constantly certain amount of the fulfilled solution merges in the sewerage and at the same time the same quantity of fresh is added to a tank.
Control of work of an artificial kidney. Chemical control of composition of the dialyzing solution is carried out by method of flame photometry (definition of ion concentration of sodium, potassium, etc.) - If it is about system of recirculation, then one definition at the beginning of dialysis suffices.
In the systems working «for discharge» the composition of the dialyzing solution constantly is controlled by means of saline testers. Two devices are usually used to increase reliability of observation. Operation of saline testers in turn also periodically is exposed to check by means of flame photometry (see) or osmometriya (see. Osmotic pressure ).
In addition to chemical control, during a hemodialysis constant control behind temperature of the dialyzing solution is required. All systems of a hemodialysis are supplied with heaters and temperature regulators which automatically maintain set-point temperature of solution.
During the work with the bicarbonate buffer apply blowing off to stabilization of pH of the dialyzing solution its mix of oxygen and carbon dioxide gas and therefore frequent control of pH of solution is required.
Modern devices of Nominative include the monitors providing control of pressure of blood in the device, hits of air in a blood stream of the patient, leak of blood in the dialyzing solution and also speeds of passing through Nominative of the dialyzing solution and its pressure in the dialyzer. Measurement of size of ultrafiltration during a hemodialysis is carried out by hl. obr. by means of a bed scales, not entering Nominative. At disturbance of an integrity of a membrane and an exit of blood in the dialyzing solution automatic systems of the termination of a hemodialysis work. Use so-called detectors of level, or air detectors which watch the level of blood in the special camera (a trap of air) of the venous highway that the possibility of an air embolism reliably warns. Sensors of pressure control the level of positive pressure of blood in the dialyzer. Speed of the movement of solution can also widely vary and therefore almost all devices of Nominative are supplied with flowmeters (floumetr).
Safety of the patient is based that in Nominative there are devices which in case of increase or understating of the set conditions give light and audibles signal of alarm. In certain cases, as, e.g., at exceeding of the established pressure of blood, at hit of air in kroveprovodyashchy system, blood in the dialyzing solution, at temperature increase of the dialyzing solution above the established borders, the flow of blood and dialysis automatically are interrupted. Interruption of a flow of blood is carried out by means of electromagnetic clips.
Sterility and an apirogennost of dialyzers and kroveprovodyashchy system are more reliable in one-time devices. All elements which during dialysis have contact with blood of the patient collect industrially, pack and will sterilize by means of ethylene oxide, gamma irradiation or formalin. An essential lack of systems disposable — their high cost. Therefore dialyzers of repeated use still are widely used. In these cases preparation of the device for work is carried out directly in to lay down. establishment. Before the use the dialyzer and highways of blood fill 2% with solution of formalin that gives the fullest sterilizing effect. Just before operation the system is washed sterile fiziol, solution with heparin (2 l fiziol, solution are required). Preparation of the device for work takes only 30 — 40 min. The system of the dialyzing solution is periodically subjected by sterilizations by formalin. It is especially important for devices with recirculation since in this case bacterial pollution of system of dialysis happens very quickly that can lead to emergence of the pyrogenic reactions due to penetration of bacterial toxins through a membrane.
Nonconventional forms of extrarenal clarification of blood
New approach to creation of Nominative is offered by Henderson and soavt. (1967) the principle called by them a diafiltration. It is based on bystry removal by means of special membranes of an ultrafiltrate of plasma with simultaneous completion of losses of water and electrolytes according to specific conditions of treatment. Advantage of such approach is that at ultrafiltration it is almost equally well possible to delete both low-molecular, and middlemolecular metabolites. Believe that among the last there are substances responsible for displays of uraemic intoxication which at a traditional hemodialysis are removed much worse, than low-molecular. It is necessary to carry to advantages of a method as well an exception of a design of the device for preparation and supply of the dialyzing solution.
Other direction is regeneration of the dialyzing solution. The devices created for this purpose allow to conduct a hemodialysis at continuous recirculation of limited amount of the dialyzing solution (5 — 30 l). In this case dimensions of Nominative are sharply reduced.
Further improvement of Nominative, working by such principle, allows to count on creation in the future wearable the patient of a small-size artificial kidney. The first prototypes of such systems are already developed. Other approach to creation of a wearable artificial kidney is based on use of the small ultrafiltering adaptation connected to vessels of the patient. The received ultrafiltrate can be exposed to regeneration (e.g., with use of adsorbents).
The original approach to development of devices for extrarenal clarification of blood based on use of so-called artificial cells is offered by Cheyng (T. Chang, 1969). Artificial cells represent the microcapsules covered with a semipermeable membrane containing the substrate capable to absorb or provide the necessary transformations of metabolites or toxins (e.g., sorbents, ionites, enzymes). The devices containing the encapsulated active coals use as addition of a usual hemodialysis, and at poisonings their use has independent value. Cartridges with the encapsulated sorbent connect to blood vessels of the patient as well as. item.
Bibliography: Deryabin I. I. and Lizanets M. N. Artificial kidney, M., 1973, bibliogr.; Pytel A. Ya. and d river. Artificial kidney and its clinical use, M., 1961; D i t t of i with h P. u. a. Hamodialyse und Peritonealdialyse, B. u. a., 1970, Bibliogr.; Fritz K. W. Hamodialyse, Stuttgart, 1966; Renal dialysis, ed. by D. Whelpton, Philadelphia, 1974.
E. B. Gorbovitsky, G. P. Kulakov, E. R. Levitsky.