Technical Information

This alternative arose after exhaustive research into how patients were treated in the 20th century, when the intestine was very important for treating those patients and was later displaced with the advent of catheters for peritoneal dialysis and hemodialysis; it was called intestinal dialysis, J. Hamburger (1968).

Currently, Dirokad can be considered a gastrointestinal dialysis process since it is a procedure in which an electrolytic solution with a cathartic is passed through the digestive tract to reduce nitrogenous elements in the blood, relieving the discomfort caused by uremic toxins responsible for the uremic syndrome. This process is carried out by gradient-time and allows molecules and atoms to pass between the blood and the circulating dialysis fluid, in the same way as peritoneal dialysis with the parietal and visceral peritoneal membranes or the synthetic cartridge in Hemodialysis or extracorporeal dialysis.

Jean Hamburguer in his Nephrology book (1968) states that since 1950 the intestine had been very useful for treating patients with renal failure and it was called intestinal dialysis.

The first demonstration of the clinical value of Gastrointestinal Dialysis was reported by R. Phillips and Colsen, 1976.

Over time, we have seen different procedures to avoid or remove uremic toxins, as well as to correct body fluids and electrolytes, such as:

1. Since the 1960s, Giovannetti (1964) demonstrated the value of an almost protein-free diet with only pasta; although urea did not rise considerably, patients became malnourished and still presented uremic syndrome, and therefore it stopped being used
2. The use of activated charcoal has also been used to reduce urea, H. Yatzidis (1976), and for drug detoxification in kidney injuries caused by vancomycin in children, etc.
3. The use of starches and oxycelluloses as urea sorbents increases intestinal nitrogen elimination and reduces urea production, Eli A. Friedman (1976).
4. Escherichia coli modified by genetic engineering has been used in uremic rats to break down urea at the intestinal level by ingesting urease through the intestinal tract; however, they are specific for reducing urea but not the rest of the “uremic toxins,” Thomas Ming Swi Chang (2000).
5. The first perfusion in an intestinal loop for the treatment of uremia was performed by Fine J. (cit
6. in 1946.
7. Subsequently, the entire intestine was perfused to reduce urea in chronic uremic patients, observing a urea removal of 1.1 g per hour and estimating intestinal urea clearance at 27 ml/min and creatinine at 7 ml/min, Young T. K., Phillips R. (1997).
8. Using a surgically isolated intestinal segment to perfuse the dialysis fluid, patients tolerated daily treatment for a period of 3–6 hours, even with hypertonic solutions for cases of oligoanuria. The disadvantage has been the need for surgery and the persistent presence of stomas in the abdominal wall, Panteras (1964)
9. An attempt has been made to isolate an intestinal segment for exclusive and constant use for dialysis, but due to the harshness of the process it has not been practical. This showed that half of the small intestine can transfer predictable amounts of water, electrolytes, and crystalloids, as well as amino acids and carbohydrates, Parisi R. (1972).

It has been proven that the digestive tract serves as a permeable membrane to molecules such as uremic toxins when it is in contact with a dialyzing solution on one side and, on the other, the bloodstream—as proposed by (the author) in the journal Nephron (1964). When it has been used as a means for drug detoxification with activated charcoal or in patients with CKD as renal replacement therapy.

The adult digestive tract measures approximately 5 meters; the intestine, with its folds, villi, and filaments, is potentially a very large and important contact surface, F. H. Netter (1962), through which the exchange of molecules and atoms by diffusion can take place—an alternative for removing toxins in patients with CKD.

The gastrointestinal tract potentially serves as an alternative route to remove uremic waste; hence intestinal dialysis was proposed more than a century ago by the French physiologist Claude Bernard, who in 1847 observed that dogs after bilateral nephrectomy eliminated large amounts of urea through the intestinal mucosa. Among the solutes eliminated daily via the intestine in a uremic patient are 70 g of urea, 2.9 g of creatinine, 2.5 g of uric acid, and 2 g of phosphates—much higher than those eliminated by a normal kidney in 24 hours. Sparks R. E. (1979).

Considering that the outer part of the digestive tract is used as a permeable membrane in peritoneal dialysis, inside the intestine cellular permeability is much greater due to its large absorptive surface. Thus, when an electrolytic solution with a cathartic flows through its interior, the transport of molecules, electrolytes, and uremic toxins between the blood and the fluid circulating in the intestine takes place, from a physical and chemical standpoint, in a process similar to peritoneal dialysis.

Dialysis, by replacing some functions of a healthy kidney, keeps patients with end-stage CKD free of symptoms by extracting solutes accumulated in the blood such as urea, creatinine, uric acid, water, and electrolytes, as well as other substances such as organic acids, sulfates, phosphates, and other uremic toxins like the so-called middle molecules (MM), which are not routinely measured in the laboratory due to high cost and process difficulties and are only measured for research, Uremic Toxicity (1978).

The use of permeable membranes in the treatment of CKD—whether natural, such as the parietal and visceral peritoneum, or synthetic—is not different in function from what we have inside the digestive tract. Netter (citation) has considered that if we imagine the digestive tract unfolded and extended, due to its folds, filaments, and villi, it would be like a soccer field where, with such an extensive surface, exchange occurs between the blood and the intestinal lumen in both directions—water, electrolytes, and uremic toxins. P. R. Schloerb, (1964).

Dirokad is a composition of different salts aimed at delaying the implementation of conventional dialysis methods (peritoneal or hemodialysis) in chronic kidney failure; it is a gastrointestinal dialytic solution, taken orally, improving quality of life and being more accessible for people.

By orally ingesting the gastrointestinal dialytic solution—which is seven liters per session in adults, over a period of approximately four hours—the gastrointestinal tract performs osmosis and diffusion, eliminating toxins by gradient-time and producing an osmotic diarrhea induced precisely by this formula.

The most important characteristics of DIROKAD are that no surgery is required, nor the use, for example, of peritoneal catheters or vascular access as in peritoneal dialysis or hemodialysis; it involves only oral doses of a dialytic solution.

Understanding that dialysis means the passage of small and intermediate molecules through a permeable membrane (synthetic, as in hemodialysis, or natural, as in peritoneal dialysis). Through the intestine, proteins, carbohydrates, fats, and medications are absorbed, and toxins such as urea, creatinine, and phosphates are eliminated from the blood into the intestine. Thus, during the 4 to 5 hours in which an electrolyte solution without toxins circulates through the intestinal tract as a result of a cathartic, intestinal dialysis takes place, tending to balance electrolyte concentrations between the blood and the Dirokad solution, in the same way as peritoneal dialysis.

Due to the osmolarity of the dialytic solution, ingesting it results in osmotic diarrhea, which prevents absorption into the blood and avoids fluid overload, thereby allowing the constant and relatively rapid administration of the solution and achieving the desired balance.

The main advantages of using Dirokad are:

1. It delays the need for peritoneal dialysis and hemodialysis procedures, which are invasive,
2. It avoids surgeries for catheter placement.
3. There are no infection risks.
4. Transfers to dialysis units are avoided.
5. Improved quality of life, as it is a procedure performed at home and at most once a week.
6. Applicable in rural settings without risk.
7. No training or special care required.

Dirokad helps the body perform what we know as dialysis, through the passage of substances across the intestinal cell membranes, using its lumen on one side and, on the other side, the blood—seeking the passage of solutes in both directions through intercellular spaces. A person with kidney failure takes this formula orally, and the small and large intestine initiate a process of solute diffusion between those contained in the patient’s blood and those in the dialytic solution. Solute diffusion will tend to balance the amount of solutes in the blood and in the dialytic solution, thus tending to normalize the concentrations of such compounds in the blood of the person with CKD.

To avoid an electrolyte loss greater than necessary from the blood, the gastrointestinal dialytic solution contains concentrations of such compounds in amounts sufficient to achieve balance.
 
The way the chemical diffusion process is leveraged for the person who ingests the gastrointestinal dialytic solution is similar to how it is leveraged in peritoneal dialysis, but the key peculiarity of the formula described is that in this method the semipermeable membrane for solute transfer is composed mainly of the mucosa of the digestive tract, as well as the basement membrane of the blood vessels surrounding it. Thus, the solutes to be eliminated move from the bloodstream to the gastrointestinal tract. On the other hand, the formula of this gastrointestinal dialytic solution contains an element that, due to the large size of its molecules, does not cross the semipermeable membrane and induces an osmotic reaction that accelerates the transfer of solutes to be eliminated. The entire process of solute exchange using the walls of the digestive tract is enhanced by how extensive its contact surface is with DIROKAD, since the gastrointestinal tract is sufficiently broad to allow a solute movement as large as necessary and remove undesirable toxic compounds from the body.

References