RU2261702C1 - Method for treatment of hyperhomocystenemia in patients with chronic renal insufficiency and treated by heme-dialysis or heme-filtration - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: before onset of treatment or in the process of treatment patient is administrated 2,3-dimercaptopropane sodium sulfonate in the dose 50-500 mg by subcutaneous or intramuscular route depending on the patient mass and the expression degree of hyperhomocysteinemia. Method provides normalization of blood level homocysteine due to its elimination from body as reduced homocysteine after its complete release from blood protein-bound form and with retention of these proteins in circulation. Invention can be used in treatment of patients with renal insufficiency with the enhanced blood content of homocysteine who have increased concentration of low- and mean-molecular metabolites due to disturbance in urine formation and when carrying out heme-dialysis or heme-filtration is required.

EFFECT: improved treatment method.

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Description

The invention relates to medicine and can be used for the treatment of patients with renal failure (CRF) with high blood homocysteine, in which, due to a violation (or complete cessation) of urine formation in the blood, the concentration of low and medium molecular metabolic products increases sharply, which requires hemodialysis or hemodiafiltration.

Hemodialysis and hemodiafiltration are options for extracorporeal renal replacement therapy (RRT). PST is traditionally used to treat patients with renal failure, in which, due to a violation (or complete cessation) of urine formation in the blood, the concentration of low- and medium-molecular metabolic products increases sharply.

These treatment methods relate to processes in which the liquid and substances dissolved in it are removed or introduced into the blood circulating outside the patient's body. During this process, blood is constantly (for several hours) circulating through a dialyzer or hemofilter, which is a bunch of hollow capillaries with semipermeable membranes. Inside these capillaries is the patient’s blood, outside the dialysis fluid (dialysate), while the flows are directed in opposite directions. During hemodialysis, during this counterflow, an exchange of substances occurs between blood and dialysate - harmful substances and excess water are removed from the blood by the diffusion mechanism. During hemofiltration, the movement of water from the blood is carried out through a semipermeable membrane with large pores by convection - together with water, the substances dissolved in it are also removed. Compensation of water loss by blood is carried out by simultaneous intravenous administration of special solutions. Hemodiafiltration is a combination of hemodialysis and hemofiltration technologies - removal of excess fluid and dissolved substances from the patient’s body occurs by diffusion and convection simultaneously (HRBrady, CSWilcox Therapy in Nephrology and Hypertension. 2 ^nd edition, Elsevier Science Ltd, 2003, 1006 pp).

An increase in the concentration of homocysteine (Gci) in the blood causes severe impairment of vascular endothelial function and is an important risk factor for vascular diseases. In the overwhelming majority of patients with renal insufficiency receiving treatment with RRT, the concentration of Gc exceeds the normal values due to the complete or almost complete loss of renal function. Therefore, the decrease in the content of Gci is an important task in the treatment of patients with PST.

At the same time, hemodialysis or hemodiafiltration per se only lead to a slight decrease in blood Gc (up to 30%).

Attempts to lower the concentration of homocysteine during hemodialysis using reducing agents have previously been made using N-acetylcysteine, another reducing agent that acts through active SH groups. One study did not find a significant decrease in Gc during 4-week oral therapy with N-acetylcysteine (Friedman AN; Bostom AG; Laliberty P; Selhub J; Shemin D. The effect of N-acetylcysteine on plasma total homocysteine levels in hemodialysis: a randomized , controlled study Am. J. Kidney Dis 2003 Feb; 41 (2): 442-6 (ISSN: 1523-6838)). In another study, prolonged intravenous administration of this substance during 1 hemodialysis procedure led to a decrease in the concentration of homocysteine in the blood of patients.

The problem that is solved by the invention is to create a method for the treatment of hyperhomocysteinemia in patients with chronic renal failure, in which the concentration of homocysteine in the blood plasma is significantly reduced.

The problem is solved as follows. A method of treating hyperhomocysteinemia in patients with chronic renal failure receiving hemodialysis or hemodiafiltration treatment differs in that 50-500 mg of 2,3-dimercaptopropanesulfonate sodium is administered subcutaneously or intramuscularly before the indicated treatment or in the process, depending on the patient’s weight and severity of hyperhomocysteinemia.

Sodium 2,3-dimercaptopropanesulfonate is a traditional remedy used for poisoning with organic and inorganic compounds of arsenic, gold, mercury, cadmium, cobalt, copper, zinc, nickel, bismuth, antimony, as well as preparations of cardiac glycosides. In addition, indications for the use of this drug are diabetic and alcoholic polyneuropathy, hepatocerebral degeneration. The mechanism of action of sodium 2,3-dimercaptopropanesulfonate is determined by the binding of active sulfhydryl groups of the molecule to ions or substances in the blood and tissues that can block thiol groups of enzymes and inactivate them with the formation of non-toxic water-soluble complexes (Encyclopedia of Medicines, edited by G.L. Vyshkovsky, Register of Medicinal Products of Russia, 2004, p.892).

A method of treating hyperhomocysteinemia in patients with chronic renal failure consists in the fact that during the hemodialysis / hemodiafiltration session, 50-500 mg of sodium 2,3-dimercaptopropanesulfonate is administered subcutaneously or intramuscularly before the indicated session, depending on the patient’s weight and severity of hyperhomocysteinemia.

After the treatment, the concentration of Gci decreased almost to normal and this decrease was significantly more pronounced in comparison with the isolated hemodialysis / hemodiafiltration efficacy.

The invention is illustrated by examples.

EXAMPLE 1. Patient K., born in 1940 Diagnosis: Chronic sclerosing glomerulonephritis, terminal renal failure. Hemodialysis treatment began on September 21, 2002. Secondary arterial hypertension. IHD: coronary arteriosclerosis, atherosclerotic cardiosclerosis. Calcification of the aorta and mitral valve. Cholelithiasis. Chronic calculous cholecystitis without exacerbation. Of the patient's characteristics, it should be noted high (up to 210-220 / 110-120 mm Hg) arterial hypertension ("working" blood pressure of about 180/100 mm Hg), which is apparently not associated with hyperhydration.

The level of total plasma homocysteine in the patient was more than 30 μmol / L (30.78 μmol / L - moderate hyperhomocysteinemia). After a standard 4-hour hemodialysis session, the level of GcI decreased by 20% to 24.44 μmol / L. 06/28/2004, 30 minutes before the start of hemodialysis, the patient was injected 3.0 ml of a 5% solution of 2,3-dimercaptopropanesulfonate sodium subcutaneously, which led to a marked decrease in Gci by 61.6% compared with the concentration of this substance before hemodialysis. The level of GCI before hemodialysis is 31.92, after dialysis - 12.25 μmol / L (normal).

EXAMPLE 2. Patient M., born in 1975 Diagnosis: Membrane-proliferative glomerulonephritis in the stage of renal sclerosis, terminal renal failure. Hemodialysis treatment started on September 21, 1994. Chronic viral hepatitis C, HCVAb +, with low activity. Secondary hyperathyroidism, diffuse osteoporosis, moderate. Kidney autotransplantation on 10/11/1997, acute rejection crisis, graft removal on 11/15/1997

Young patient, safe (of complications - only the initial manifestations of osteopathy as well as moderate anemia) despite the relatively long duration of dialysis treatment with poor adherence to the water regime and diet.

The level of total plasma homocysteine in the patient was 24.69 μmol / L - mild hyperhomocysteinemia. After a standard 4-hour hemodialysis session, the level of GcI decreased to 15.86 μmol / L (by 35.8%). 06/28/2004, 30 minutes before the start of hemodialysis, the patient was injected with 5.0 ml of a 5% solution of 2,3-dimercaptopropanesulfonate sodium subcutaneously. The decrease in the Gc content during the dialysis session was more significant and amounted to 84%. The Gci level is 18.53 before hemodialysis and 2.96 μmol / L after dialysis (normal). There was a local reaction to the introduction of the drug in the form of a blister that disappeared after the application of the ointment "Flucin" in about 3 hours.

EXAMPLE 3. Patient K., born in 1949 Diagnosis: Chronic glomerulonephritis in the stage of renal sclerosis, stage III renal failure. Hemodialysis treatment started on May 16, 2001. Chronic viral hepatitis C + B with moderate cytolytic activity.

At the time of the examination, the patient was temporarily transferred from hemodialysis to hemodiafiltration treatment. The indication for translation was the presence of neurological symptoms of the type of restless legs syndrome, the reason for the development of which, apparently, is not associated with an insufficient dose of dialysis and is still not clear.

The plasma Gc level in the patient was 26.79 μmol / L - moderate hyperhomocysteinemia. After a 4-hour hemodiafiltration session, the GcI level decreased to 15.74 μmol / L (41.2%). June 28, 2004, 30 minutes before the start of hemodiafiltration, the patient was injected with 4.0 ml of a 5% solution of 2,3-dimercaptopropanesulfonate sodium subcutaneously. The decrease in the Gc content during the dialysis session turned out to be more significant: the Gc level before the procedure was 42.54, after that it was 12.57 μmol / L (a decrease of 70.4% to the norm). No adverse reactions to drug administration were observed.

EXAMPLE 4. Patient G., born in 1974 Diagnosis: Hemorrhagic vasculitis, secondary chronic glomerulonephritis in the stage of renal sclerosis, terminal renal failure. Hemodialysis treatment began on 10/06/1994. Allograft of the kidney 06/18/2001. Transplant cystoma, transplantectomy 12/26/2002, the resumption of chronic hemodialysis. Secondary arterial hypertension. Secondary hyperparathyroidism.

During the examination, he received hemodiafiltration treatment. The patient's plasma Gc level was 28.62 μmol / L - moderate hyperhomocysteinemia. After a 4.5-hour hemodiafiltration session, the Gc level did not change: 28.62 µmol / L before and 29.86 µmol / L after the HDF session. 06/28/2004, 30 minutes before the start of the HDF session, the patient was administered 6.0 ml of a 5% solution of sodium 2,3-dimercaptopropanesulfonate subcutaneously. A marked decrease in Gci was noted after the treatment session: the level of Gci before HDF was 29.93 mmol / L, after - 5.38 mmol / L (-81.9%).

EXAMPLE 5. Patient G., born in 1946 Diagnosis: Chronic glomerulonephritis in the stage of renal sclerosis, terminal renal failure. Hemodialysis treatment started on September 29, 1991. Dialysis osteopathy: secondary hyperparathyroidism, dialysis amyloidosis, carpal tunnel syndrome on the right. Chronic viral hepatitis C, HCVAb +, with low cytolytic activity.

The level of total plasma homocysteine in the patient was 27.83 μmol / L - moderate hyperhomocysteinemia. After a 4.5-hour hemodialysis session, the GCI level decreased from 27.83 µmol / L to 16.8 µmol / L (-39.5%). 06/28/2004, 30 minutes after the start of hemodialysis, the patient was injected 10.0 ml of a 5% solution of 2,3-dimercaptopropanesulfonate sodium subcutaneously. The decrease in the Gc content during the dialysis session was 64%: the Gc level after dialysis decreased from 43.4 to 14.63 μmol / L. No adverse reactions to drug administration were observed.

Thus, the use of sodium 2,3-dimercaptopropanesulfonate in case of hyperhomocysteinemia in patients with chronic renal failure receiving hemodialysis / hemodiafiltration treatment contributes to a significant decrease in homocysteine concentration, which opens up new perspectives in the treatment of hyperhomocysteinemia in patients with PST.

Claims (1)

A method of treating hyperhomocysteinemia in patients with chronic renal failure receiving hemodialysis or hemodiafiltration treatment, characterized in that 50-500 mg of sodium 2,3-dimercaptopropanesulfonate is administered subcutaneously or intramuscularly prior to treatment or in the course of treatment, depending on the patient’s weight and severity of hyperhomocysteinemia .