RU2414896C1 - Method of preventing contrast-induced nephropathy during radio-opaque examination - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention relates to medicine, in particular to radiology and nephrology, and can be applied for prevention of contrast-induced nephropathy before carrying out radio-opaque examination. For this purpose introduced is cytoflavin in dose 1 pill 3 times per day 2-5 days before carrying out radio-opaque examination.

EFFECT: method makes it possible to protect cells of renal channels from toxic action of radio-opaque combination due to improvement of energy processes in cells and tissues by regulation of two most important stages of Krebs cycle: including pyruvic acid and its oxidation to acetyl CoA, as well as oxidative decarboxylation of a-ketoglutaric acid, which results in reduction of depression of activity of succinate dehydrogenase of peripheral blood lymphocytes.

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Description

The invention relates to medicine, namely to medical radiology and nephrology, and can be used to prevent contrast-induced nephropathy (CIN) before radiopaque studies in children.

Contrast-induced nephropathy (CIN) is a serious but potentially preventable complication that develops with the use of contrasting iodine-containing substances. Predisposing factors for the development of CIN are considered to be elderly or young, the presence of nephropathy with reduced kidney function, diabetes mellitus, dehydration, anemia, and the use of non-steroidal anti-inflammatory drugs.

In recent years, the number of studies on the mechanisms of development of contrast-induced nephropathy (CIN) and methods for its prevention and treatment has been increasing. The emergence of new data on this issue allows us to make more informed recommendations on the choice of the safest radiopaque contrast medium (CSW) and give practical advice on conducting a study using CS.

Excretory urography as a way of radiopaque studies in children, in addition to determining the functional state of the kidneys, pelvis and ureters, allows us to get an idea about their morphological state. However, the morphological state of the urinary tract can be detected on the urogram only if the kidney is functioning satisfactorily. As the renal function decreases, the density of the shadow of the contrast medium in the radiograph decreases accordingly.

Modern methods of medical imaging provide for a large number of modifications of contrast studies that require the use of radiopaque agents (RKS). These funds are improved by manufacturing companies and have evolved from high osmolarity to iso- and low osmolarity. The use of highly osmolar agents is associated with the description of numerous cases of contrast-induced nephropathy (CIN), which manifests itself as a decrease in glomerular filtration rate of varying severity, up to acute renal failure. The development of severe CIN not only endangers the life of the patient, but also requires the use of expensive treatments - dialysis and intensive care.

Since the nephrotoxic effect of PKC is dose-dependent, it is recommended to use the lowest possible dose, with the choice of a suitable PKC being important. It was shown that the frequency of CIN in patients with renal failure and diabetes mellitus is lower when using isoosmolar CSWs (iodixanol) than when using low-osmolar CSWs (iopromide, iohexol, iobitridol). It has been shown that the administration of calcium channel blockers, dopamine and N-acetylcysteine reduces the frequency of CIN (Norbert H. Lameire. Contrast-induced nephropathy - prevention and risk reduction. Nephrology Dialysis Transplantation 2006, 21 (Supplement 1): pp.11-23) .

From various medical literature sources, the following methods for preventing CIN are known.

A known method of active hydration of a patient (fluid load up to 5% of body weight) (Trivedi HS, Moore H., Nasr S., et al. A randomized prospective trial to assess the role of saline hydration on the development of contrast nephropathy. Nephron Clin Pract 2003; 93: C29-C34).

This method affects only the prerenal mechanisms of CIN.

The disadvantage of this method is the undesirable effects in patients with congestive heart failure, arterial hypertension and hyponatremia.

A known method of alkalizing the body by the introduction of solutions of sodium bicarbonate (Merten GJ, Burgess WP, Gray LV, et al. Prevention of contrast induced nephropathy with sodium bicarbonate-A randomized controlled trial. JAMA 2004; 291: 2328-2334), which is also associated with volumetric expansion.

The disadvantage of this method is active alkalinization, which can cause hypokalemia due to the transport of potassium into the cells and is accompanied by muscle hypotension and cardiac arrhythmias.

A known method, which consists in the prophylactic administration of theophylline, an adenosine antagonist that helps stimulate renal blood flow, but is also not a clinically effective tool. Moreover, side effects are possible with its use: tachyarrhythmia, epileptic seizures, dyspepsia and shock reactions (Bagshaw SM, Ghali WA Theophylline for prevention of contrast-induced nephropathy: A systemic review and meta-analysis. Arch Intern Med 2005; 165: 1087 -1093).

Thus, the currently known methods for preventing CIN are not sufficiently effective, and the spectrum of their adverse reactions makes it impossible to use them, especially in pediatric practice.

It is known to use acetylcysteine with antioxidant and cyprotective properties for the prevention of CIN. The drug is a thiol-containing antioxidant that acts as a potential eliminator of free radical substances, as well as a stimulator of the synthesis of nitric oxide, a potential vasodilator that resists ischemic and toxic effects. Although the use of acetylcysteine seems relatively safe, its effectiveness in clinical studies has not been proven (Nallamothu BK, Shojania KG, Saint S., et al. Is acetyicysteine effective in preventing contrast-related nephropathy? A meta-analisis. Am J Med 2004; 117 : 938-947). This method is chosen by us as a prototype.

The present invention is to develop a method for the prevention of contrast-induced nephropathy.

The technical result is to prevent the toxic effects of radiopaque substances on cellular energy metabolism and, as a result, reduce the risk of contrast-induced nephropathy.

The invention consists in the use of cytoflavin for prophylactic CIN in radiopaque studies. The drug is prescribed 1 tablet 3 times a day for 2-5 days before the X-ray contrast study, which improves the energy processes in cells and tissues by regulating the two most important stages of the Krebs cycle: the inclusion of pyruvic acid - its oxidation to acetyl CoA and oxidative decarboxylation α- ketoglutaric acid.

Cytoflavin is a complex preparation, which includes well-known medicinal substances that are widely used for various diseases in an isolated form: riboxin 200 mg, succinic acid 1000 mg, riboflavin 20 mg, nicotinamide 100 mg. The pharmacological effects of the drug are represented by the sum of the effects of its constituent components. The metabolic role of succinic acid is discussed above. Riboxin is an agonist of purinergic receptors that are part of ligand-controlled ion channels. With the excitation of purinergic receptors, hyperpolarization of the cell membrane occurs. The metabolotropic component in the action of these receptors leads to the formation of additional energy regardless of the glycolytic pathway. Moreover, due to metabolites of adenosine, glycolysis may be activated. Riboflavin and nicotinamide are components of redox coenzymes that preserve and maintain many metabolic reactions involved in proton transfer from the Krebs cycle (including the mitochondrial oxidative phosphorylation cascade) involved in the recovery of the glutathione pool (Russian Drug Register. Encyclopedia of Medicines, 2009).

Cytoflavin belongs to the group of metabolic agents and has pronounced antioxidant and neurotropic effects, normalizing the processes of oxygen utilization by tissues that have already experienced hypoxia, and also improves hemorheology and increases the immunobiological resistance of the body (Afanasyev V.V. Cytoflavin in intensive care: A manual for doctors. St. Petersburg. : VMEDA, 2005, p. 36).

A group of 22 children with various options for obstructive and non-obstructive nephropathies was prescribed cytoflavin, which was started 2-5 days before excretory urography at a dose of 1 tablet 3 times a day.

A decrease in the inhibition of the activity of peripheral blood lymphocyte succinate dehydrogenase one day after the administration of CSW was reliably detected compared with the control group of 37 children who did not receive cytoflavin.

At the same time, the test group did not show signs of a decrease in glomerular filtration rate and electrolyte disorders, blood pressure remained stable.

Clinical examples of the method

Example 1. Patient Zhenya R., 14 years old, was admitted to the urology department of the SCCH RAMP with a diagnosis of chronic pyelonephritis, corrected ureterohydronephrosis on the right, for a follow-up x-ray examination, during which excretory urography was performed. Before excretory urography, the level of serum creatinine was 65 μmol / L, Na - 140 mmol / L, K - 4.4 mmol / L, pH 7.358, CB - 20.1 meq / L; clearance of endogenous creatinine - 125.4 ml / min. Blood pressure was 115/70 mmHg. He didn’t receive any medications; he consumed the usual amount of fluid. As a radiopaque agent, iodixanol in a dose of 60 ml was used. Excretory urography transferred satisfactorily.

After 24 hours, the level of serum creatinine was 82 μmol / L, glomerular filtration rate decreased to 91 ml / min, Na - 132 mmol / L, K - 5.2 mmol / L, pH 7.33, CB - 20 meq / L. The activity of succinate dehydrogenase (SDH) of peripheral blood lymphocytes decreased from 67419 ± 5818 conventional units up to 47570 ± 2279 conventional units (p≤0.05), and α-glycerophosphate dehydrogenase (α-GFDH) decreased from 7.5 ± 0.68 to 4.3 ± 0.63 g / LF (p≤0.05) (Figure 1).

Creatinine levels decreased to baseline after 3 days, indicating a reversible pattern of renal functional impairment corresponding to a mild degree of contrast-induced nephropathy.

Example 2. Patient Ira G., 10 years old, was admitted to the urology department of the NCHA RAMA with a diagnosis of chronic pyelonephritis, corrected vesicoureteral reflux of the third degree on the right, bullous cystitis, for follow-up x-ray examination, during which excretory urography was performed. Within 5 days before the study, the patient received a complex preparation of cytoflavin in a dose of 1 tablet 3 times a day. Before excretory urography, the level of serum creatinine was 70 μmol / L, Na - 137.6 mmol / L, K - 4.1 mmol / L, pH 7.39, CB - 20.8 meq / L, endogenous creatinine clearance 95 ml / min Blood pressure was 105/60 mm RT. Art. Before the planned examination, the child consumed a sufficient amount of fluid. As a radiopaque agent, iodixanol in a dose of 50 ml was used. Excretory urography transferred satisfactorily.

After 24 hours, the level of serum creatinine was 72 μmol / L, Na - 138, 2 mmol / L, K - 4.2 mmol / L, pH - 7.39, CB - 20.9 meq / L, glomerular filtration rate not changed - 93 ml / min. The activity of LDH in peripheral blood lymphocytes remained virtually unchanged at 67453 ± 7254 and 69718 ± 55b3 srvc, α-GPDH increased insignificantly from 4.9 ± 0.71 to 6.3 ± 0.80 g / LF. Against the background of the prophylactic use of cytoflavin, no adverse effects on renal function were detected (Figure 1).

The detected differences in cytochemical indices reflect the effect of cytoflavin on maintaining energy processes in cells, which consists in maintaining the activity of succinate dehydrogenase, one of the key enzymes of the Krebs cycle (Figure 2).

Cytoflavin helps protect the renal tubule cells from the toxic effects of PKC and can be effectively used as a prophylactic against the development of CIN. Contraindications to the use of cytoflavin and side effects have not been established.

Claims (1)

A method for the prevention of contrast-induced nephropathy in X-ray contrast studies, including the use of a drug having antioxidant and cytoprotective properties, characterized in that cytoflavin is prescribed as such a drug 3 times a day 2-5 days before the X-ray contrast study.

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