Problems and solutions for artificial kidney.

Abstract

The uremic syndrome is the prototype of a slowly progressive endogenous intoxication, when a detoxifying organ (in this case the kidney) fails. It is characterized by the gradual retention of a host of metabolites, which is in part corrected by dialysis, allowing survival with an acceptable quality of life. This paper reviews the main problems of hemodialysis today, and possible solutions. Adequacy of dialysis is estimated currently from the concentration of urea, which is used as a marker molecule. The problem is that urea is not really toxic by itself. Other markers with known toxicity, such as middle molecules (300-12,000 D) and protein bound compounds should be considered. The question then arises whether the classical dialytic concept based on diffusion should be modified. Adsorptive systems may be strong binders of protein bound solutes. Other concepts that are now arising, and that may add to toxin removal, are slow and daily dialysis. Another question that could be raised is whether it would not be possible to support toxin removal, by administering peroral sorbants. Dialysis patients are prone to vascular disease and die early from cardio-vascular complications. One of the solutions for this problem could be to bring the blood of dialyzed patients into contact with antioxidants (e.g. vitamin C or E). The risk for perdialytic hemodynamic instability is increased in many dialysis patients. The ideal solution would be to develop an "intelligent" dialysis system, whereby blood volume and plasma osmolality are sensed continuously, and ultrafiltration and dialysate sodium concentration are adapted in function of this evolution. An adequate vascular access is indispensable to perform adequate dialysis, but thrombotic/stenotic complications are frequent. This could be prevented by molecular biological modification of vascular grafts, whereby genetic information is entered into the cells, blocking the natural chain of events that otherwise unavoidably leads to neointimal hyperplasia and atherosclerosis. Another old dream is to develop a wearable artificial kidney, whereby patients can move around, and be treated 24 hours per 24 hours, in stead of being treated intermittently at a specific location by the dialysis machine. According to some authors, part of the natural renal function could be replaced by cultured renal tubular cells, which are brought in contact with the blood of the patients. It is concluded that thrilling improvements lie ahead in the future, but the following questions arise: 1) What is the cost of all these improvements? 2) Will it remain possible to reimburse all this? 3) What is going to happen in transplantation, mainly regarding improvements in immunosuppression and the development of xenotransplantation?