RU2761730C1 - Method for differential diagnostics of uremic pancreatitis and destructive pancreatitis in patients receiving renal replacement therapy - program hemodialysis - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention relates to medicine, namely, to surgery and nephrology, and can be used for differential diagnostics of uremic pseudoperitonitis and peritonitis in patients receiving renal replacement therapy - program hemodialysis. The method includes testing the blood serum, the concentrations of β2-microglobulin and macroglobulin in the blood serum are determined in patients with suspected uremic pseudoperitonitis and peritonitis upon admission to the hospital. The ratio coefficient is then calculated according to the formula K=β2M/MG×100, wherein β2M is the concentration of β2-microglobulin, mg/l, MG is the concentration of macroglobulin, mg/l, and if the value of K is less than 1, destructive pancreatitis is diagnosed, and if the value of K is greater than 1, uremic pancreatitis is diagnosed.

EFFECT: use of the invention provides a possibility of increasing the accuracy of diagnostics and differentiation of uremic pseudoperitonitis and peritonitis in patients receiving program hemodialysis.

1 cl, 2 ex

Description

The invention relates to medicine, namely surgery and nephrology, and can be used to diagnose uremic pancreatitis and destructive pancreatitis in patients receiving renal replacement therapy (programmed hemodialysis).

According to the largest national and world registries, the number of patients constantly receiving renal replacement therapy (RRT) is steadily growing every year. With an increase in the age and duration of renal replacement therapy in patients with chronic renal failure, there is an increase in the manifestations of comorbid pathology, somatic and surgical complications, causing a deterioration in the quality of life, an aggravated prognosis of the disease and an increased risk of death, characterized by high medical and social significance (Smirnov A.V. , Shilov E.M., Dobronravov V.A. et al. 2012, Tomilina N.A. et al., 2017; E.V. Shutov et al., 2019; Webster A.S. et al., 2017) ...

Over the past decades, many researchers have noted an increase in the number of surgical complications in patients on RRT, which, unfortunately, do not decrease, but rather increase and cause erroneous emergency surgical interventions (Bikbov B.T., Tomilina N.A., 2009) ...

Scientific and technical progress, advances in surgery and other biomedical sciences have not reduced mortality from surgical complications in patients, including those on RRT (programmed hemodialysis), which remains high and poorly studied (Abramova E.E., Koroleva I.E. and others, 2015)

Diagnosis of acute destructive pancreatitis is a very difficult problem at the present time. Criteria for early preoperative diagnosis of various forms of pancreatic necrosis and indications for surgical treatment have not been sufficiently developed, and therefore unnecessary diagnostic laparotomies and open drainage operations are often performed, which, in turn, increases the frequency of pyoinflammatory diseases and leads to high mortality, 2-3 % in edematous form, and from 18-20% to 25-80% in destructive forms of pancreatitis. (Mitkov, V.V. Clinical guidelines for ultrasound diagnostics / V.V. Mitkov. - M., 1996. - 322 p.).

The results of diagnostics and the choice of treatment tactics for uremic pancreatitis in patients receiving RRT procedures (programmed hemodialysis) are also disappointing, which is largely due to the irrational and untimely use of early diagnosis and differentiation of the severity of uremic pancreatitis manifestation, the lack of uniform standards and protocols for the treatment of patients in this group, prognosis diseases. (Ruggenenti P., Schieppati A., Remuzzi G. Progression, remission, regression of chronic renal diseases // Lancet. - 2001. - No. 357 (9268). - P. 1601-1608. Karpov O.E., Levchuk A L., Stepanyuk I.V. Therapeutic and diagnostic program for acute pancreatitis. // Scientific works. - Volume-1. - M. - 2008. - pp. 56-66; Matos S., Coppens E. Chronic and inflammatory pancreariris: role of cross-sectional imaging.J. Radiol. 2005. - N. 6 - P. 749-757; Shalimov S.A., Radzikhovsky M.E., Nichitaylo M.E. Acute pancreatitis and its complications. Kiev. - Naukova Dumka. - 1990. - 272 p .; Pitchumoni CS., Patel NM., Shah P. Factors influencing mortality in acute pancreatitis: can we alter them? J. Clin. Gastroenterol. 2005. - N. 9 - P. 798-814.).

Known assessment of the severity of the course of pancreatitis, which is based on the analysis of clinical and laboratory scales, which improve the accuracy of predicting the outcome of the disease and the development of septic complications. The most common systems for assessing the severity of the patient's condition and prognosis are the Ranson (1974), Glasqow (1984), Apache-2 (1984) scales

According to the analysis of the data, the Ranson scale has 54-85% sensitivity, 68-85% specificity and a negative predictive value in the diagnosis of acute pancreatitis - 92-95%. The disadvantage of the scale is the impossibility of using it in dynamics. Nevertheless, its simplicity made it possible to widely use it on the first day of the disease and accurately predict the severity of acute pancreatitis in 46 examined patients (85.2%). (Grebenko G.I., Smanilo R.M., Kuznetsov A.V., Makeev S.I.

The APACHE II scale is based on the determination of 12 physiological parameters, age and data on previous diseases to determine the overall severity of the disease (Knaus WA, Draper EA, Wagner DP, Zimmerman JE APACHE II. A severity of disease classification system // Crit. Care Med. - 1985. - No. 13. - C. 818-829.)

The most sensitive were the following parameters, indicating a high probability of necrotizing pancreatitis:

• C reactive protein> 15 mg / l (Ranson JH, Rifkind KM, Roses DF et al. (1974) Prognostic signs and the role operative management in acute pancreatitis. Surg. Gynecol. Obstet., No. 139: C. 69-81.);

• the interval between the onset of pain and the patient's seeking help less than 24 hours indicated a high likelihood of developing pancreatic necrosis (Brown A., Baillargeon JD, Hughes MD, Banks PA (2002) Can fluid resuscitation prevent pancreatic necrosis in severe acute pancreatitis? Pancreatology, 2 ( 2): 104-107.)

• hyperglycemia ≥125 mg / dL (Lankisch PG, Blum T., Brans A. et al. (2001) Has blood glucose level measured on admission to hospital in a patient with acute pancreatitis any prognostic value? Pancreatology, No. 1 (3) : Pp. 224-229.)

• an increase in hematocrit of 44% (Brown A., Orav J., Banks P.A. (2000) Hemoconcentration is an early marker for organ failure and necrotizing pancreatitis Pancreas, No. 20 (4): C. 367-372);

• leukocytosis ≥16,000;

• hypocalcemia <2 mmol / l.

In recent years, systems for the rapid and objective assessment of the severity of the pathological process and predicting the outcome of the disease based on laboratory, instrumental, clinical parameters, and anamnestic data have been actively developed. However, despite the analysis of the data, the problem of early diagnosis of uremic pancreatitis and destructive pancreatitis is still far from being resolved.

Difficulty in the diagnosis of acute pancreatitis, and especially its destructive forms, is due to the polymorphism of clinical manifestations, their low specificity, as well as the lack of clear laboratory parameters that would unequivocally indicate an inflammatory process in the pancreas.

Based on the foregoing, the lack of reliable laboratory methods for early and timely diagnosis of uremic pancreatitis and destructive pancreatitis in patients on RRT (programmed hemodialysis) complicates the choice of medical tactics.

In practical medicine, the most reliable diagnostic method for detecting uremic pancreatitis or destructive pancreatitis is computed tomography (CT), which makes it possible to establish inflammatory processes in the pancreas in 94% of cases.

However, as it turned out, the studies conducted for the first time on days are absolutely ineffective both in terms of diagnosis and in terms of prognosis of the disease, a more or less clear picture with the help of CT can be obtained only by the 7-10th day of the disease. That is why the attitude towards this expensive technique, fraught with complications associated with the administration of a contrast agent, and the technique accompanied by a rather high radiation exposure, has recently become very critical. (Munoz-Bongrand N., Panis Y., Soyer P. et al. (2001) Serial computed tomography is rarely necessary in patients with acute pancreatitis: a prospective study in 102 patients. J. Am. Coll. Surg., No. 193 (2): p. 146-152.)

The main disadvantages of computed tomographic diagnostic techniques are:

- unwanted radiation exposure to the patient and staff;

- the complexity of the process of processing the results;

bulkiness and high cost of equipment and, as a consequence, high cost of research;

- lack of equipment in small clinics and hospitals, where patients with acute abdomen are most often hospitalized;

- for a qualitative study, a thorough preparation of the intestines (cleansing enemas) is required, which can provoke the development of peritonitis, thereby aggravating the patient's condition;

- the inaccessibility of computed tomography in medical institutions of district, city, and, sometimes, regional subordination, the high cost of research and the patient's unwillingness to be exposed to radiation induce many patients to refuse such an examination, and researchers to look for other reliable diagnostic tests.

And also the ambiguous approach to the surgical treatment of necrotizing forms of acute pancreatitis, determination of indications for surgery, early diagnosis and initiation of treatment under the influence of several authoritative clinical studies were minimized (Buechler MW, Gloor B., Muller S.A. et al. (2000 ) Acute necrotizing pancreatitis: treatment strategy according to the status of infection. Ann. Surg., No. 232 (5) C. 619-626.).

Currently, the only reasonable indication for surgical treatment of necrotizing pancreatitis is infected pancreatic necrosis in combination with progressive sepsis (Lee VT, Chung AY, Chow PK et al. (2006) Infected pancreatic necrosis - an evaluation of the timing and technique of necrosectomy in a Southeast Asian population. Ann. Acad. Med. Singapore, 35 (8): pp. 523-530.)

All of the above allows us to conclude that, despite the absence of radically new approaches to solving the problem of diagnostics and choosing the tactics of therapeutic and diagnostic measures for uremic pancreatitis and destructive pancreatitis in patients receiving RRT (programmed hemodialysis), despite the currently available opportunities as a conservative and surgical therapy based on evidence-based medicine give these patients a much better chance of survival.

Currently, for the control of systemic inflammatory and immune reactions, septic complications, destructive processes and multiple organ failure, there is a wide selection of marker proteins of various groups, among which acute phase proteins (POPs), associated with inflammation and reflecting different aspects of the pathological process, play an important role ( Trubnikov G.A., 1975; Merkulov, A.G. 1989; Polevshchikov, A.V. 1997).

As a prototype, we have taken a method for the differential diagnosis of destructive pancreatitis. Investigate the level of C-reactive protein (CRP) and α2-macroglobulin (MG) in the patient's blood serum upon admission to the hospital, determine the ratio of CRP and MG concentrations, while the CRP / MG ratio above 2 corresponds to acute destructive inflammation of the pancreas, and the CRP / MG ratio below 2 indicates a decrease or absence of the inflammatory process in the pancreas (, Kchibekov E.A., Nikulina D.M. Method for the diagnosis of destructive pancreatitis // RF Patent No. 2427837).

Considering the fact that alpha-2-macroglobulin, being an inhibitor of proteinases, quite clearly manifests its properties in acute pancreatitis - its concentration decreases and correlates inversely with the severity of pancreatitis. Therefore, alpha-2-macroglobulin is an insufficiently informative protein in the diagnosis of destructive changes in the pancreas in patients receiving RRT (programmed hemodialysis), and has diagnostic value in combination with other biomarkers of inflammatory and destructive changes.

The invention is aimed at improving the accuracy of diagnosis and differentiation of uremic pancreatitis and destructive pancreatitis in patients receiving RRT (programmed hemodialysis), available for use in practical health care.

The technical result is achieved by the fact that upon admission to the hospital in patients with suspected uremic pancreatitis and destructive pancreatitis, the concentration of β2-microglobulin and macroglobulin in the blood serum is determined, and then the ratio coefficient is calculated according to the formula K = β2M / MG × 100, where β2M is the concentration β2-microglobulin, mg / l, MG - macroglobulin concentration, mg / l, and if K is less than 1, destructive pancreatitis is diagnosed, and if K is more than 1, uremic pancreatitis is diagnosed.

At the same time, in the diagnosis of many inflammatory and destructive conditions, macroglobulin has proven itself well, which, according to many researchers, is considered an indicator of inflammation and tissue destruction (Savenkov, M.S. Low-symptom acute destructive cholecystitis: comprehensive monitoring and optimization of therapeutic tactics: author's abstract thesis ... Candidate of Medical Sciences - Astrakhan, 2006. - 22 p.). And β2-microglobulin has established itself as a predictive biomarker of renal safety for use in monitoring kidney health. So β2-microglobulin has been introduced into the diagnosis of conditions in oncohematology (Zagoskina T.P., Luchinin A.S. A method for predicting the overall survival of patients with multiple myeloma // RF Patent No. Biomarkers suitable for the diagnosis of liver fibrosis // RF Patent No. 2505821 dated 01/25/2014), diagnosis of placental insufficiency during pregnancy (Chistyakova G.N., Cherdantseva G.A. A method for predicting the development of placental insufficiency during pregnancy // Patent RF No. 2300770 of 03/20/2013), kidney diseases (Dmitrieva O.V., Batyushin M.M. and biomarker signs of renal safety with predictive power for use in monitoring the state of the kidneys // RF Patent No. 2519148 dated 09.06.2014).

Thus, the presented markers in aggregate are highly sensitive indicators reflecting the state of the inflammatory process and destruction, and their comprehensive assessment provides reliable results in determining and differentiating uremic pancreatitis and destructive pancreatitis in patients receiving RRT (programmed hemodialysis).

The study of the concentration of β2-microglobulin and macroglobulin in the serum of patients with suspected uremic pancreatitis and destructive pancreatitis on admission to the hospital in the history of receiving RRT (programmed hemodialysis) (50 patients). A clear dependence of the concentration of β2-microglobulin and macroglobulin on the severity of uremic pancreatitis and destructive pancreatitis was established. High numbers of β2-microglobulin concentration were obtained in patients with uremic pancreatitis, and the macroglobulin concentration was high in destructive pancreatitis. The argumentation of the possibility of using β2-microglobulin for the diagnosis of uremic pancreatitis is the fact that in kidney diseases the concentration of β2-microglobulin in the blood plasma increases many times, as well as in patients receiving RRT (programmed hemodialysis) the concentration of β2-microglobulin due to impaired renal excretion, pronounced uremia, leads to its excessive accumulation and served as its high reliability in the diagnosis of uremic pancreatitis. In turn, macroglobulin as a sensitive marker of a destructive state, high reliability and sensitivity in the diagnosis of destructive conditions makes it possible to establish the fact of destructive pancreatitis. Before the start of treatment, in order to determine the correct tactics of treatment and diagnostic measures in these patients, the concentrations of β2-microglobulin and macroglobulin in the blood serum were studied. When determining them in serum, the patients did not abstain from food intake, no special preparations were required. Blood was collected by conventional venipuncture in vacuum containers and the serum was separated from the cells by centrifugation after the formation of a clot.

Concentrations of β2-microglobulin and macroglobulin in blood serum were determined by enzyme-linked immunosorbent assay in mg / l by commercial test systems "BIOCHIMMAK", Moscow.

Statistical processing of the results was carried out using Student's t test. The concentration of serum β2-microglobulin was higher in uremic pancreatitis (up to 30 mg / L p <0.01), compared with the concentration in destructive pancreatitis (up to 8 mg / L, p <0.05). The concentration of serum macroglobulin was higher in destructive pancreatitis, and amounted to (up to 1200 mg / l, p <0.01), compared with the concentration in uremic pancreatitis (up to 1000 mg / l, p <0.05).

The ratio was calculated using the formula:

K = β2M / MG × 100,

Where: β2M - β2-microglobulin, MG - macroglobulin.

Uremic pancreatitis was diagnosed with a score of more than 1. All patients on RRT (programmed hemodialysis) with such a score underwent RRT (emergency hemodialysis) sessions in a hospital setting. After emergency hemodialysis in these patients, the signs of uremic pancreatitis subsided and completely disappeared as RRT (emergency hemodialysis) was carried out for health reasons.

Considering the absence and decrease in the severity of uremic pancreatitis, the positive dynamics of the somatic status from the RRT (hemodialysis sessions), surgical intervention was not used in the tactics of therapeutic and diagnostic measures in this group of patients (laparoscopy, laparotomy). The therapy was carried out in a conservative way with the use in the treatment of RRT (hemodialysis sessions) for health reasons.

The proposed method was introduced into the work of the surgical department of the ChUZ KB "RZD-Medicine" and the City Clinical Hospital No. 3 in Astrakhan and was used in the examination of 50 patients. Below are the results of testing.

Example # 1.

Patient S., 54 years old, was admitted urgently to the surgical department with a diagnosis of acute pancreatitis.

He has received more than 4 years of RRT (programmed hemodialysis) procedures for health reasons in the anamnesis, the history of missing hemodialysis procedures was revealed. The patient's laboratory data were obtained: β2M = 12 mg / l, and MG = 800 mg / l. At the time of admission, the patient's ratio was calculated: K = β2M / MG × 100, and was equal to 1.5. Considering that the ratio is more than 1, as well as that the patient has a history of RRT (programmed hemodialysis) and there are missing hemodialysis procedures, according to vital indications, the patient underwent an emergency hemodialysis session. Epigastric pain decreased in intensity, and after the second hemodialysis session, signs of uremic pancreatitis were no longer observed. Considering that the β2M / MG ratio is more than 1, positive dynamics against the background of standard treatment, including detoxification, antispasmodic, antibacterial, antisecretory therapy and the obligatory RRT procedures (hemodialysis sessions) for health reasons 3 times a week for at least 240 minutes, indications for surgery the patient does not. The patient was discharged with positive dynamics on the 8th day.

Example No. 2

Patient G., 62 years old, was admitted on an emergency basis to the surgical department with a diagnosis of acute pancreatitis.

For more than 6 years, he has received RRT (programmed hemodialysis) sessions for health reasons, the patient has not been found to have missed hemodialysis procedures. In order to exclude and differentiate uremic pancreatitis, the β2M / MG ratio was calculated. The patient's laboratory data were obtained: β2M = 6.8 mg / l, and MG = 1200 mg / l. The ratio of the patient was calculated: K = β2M / MG × 100, and was equal to 0.56.

Upon admission: the patient's condition is serious, not stable. Conscious, communicative, moderate arousal. The abdomen is tense, on palpation, severe pain in the epigastrium. Considering the β2M / MG ratio of less than 1, the absence of the effect of intensive therapy, as well as CT data (destructive pancreatitis), after preoperative preparation, laparotomy, sanitation and drainage of the abdominal cavity were performed. Introoperatively: acute destructive pancreatitis, fatty and hemorrhagic pancreatic necrosis. Received intensive therapy, including detoxification, antispasmodic, antibacterial, antisecretory therapy, and also included RRT procedures (hemodialysis sessions) for health reasons 3 times a week for at least 240 minutes. The postoperative period was uneventful, without complications. The wound healed by primary intention. Discharged on the 14th day.

When using our proposed method, it is possible to achieve:

• reliable differential diagnosis of uremic pancreatitis and destructive pancreatitis in patients receiving RRT (programmed hemodialysis), even when diagnosis by other instrumental and laboratory methods is difficult;

• special conditions and preparation of the patient are not required for diagnosis;

• the method allows to diagnose latent destructive conditions that require surgical treatment;

• reducing economic costs by reducing preoperative preparation, excluding expensive computer examination, attempts at unsuccessful conservative therapy and repeated hospitalizations;

• elimination of unwanted radiation exposure to the patient and staff.

Claims (1)

A method for differential diagnosis of uremic pancreatitis and destructive pancreatitis in patients receiving renal replacement therapy - programmed hemodialysis, by examining blood serum, characterized in that, upon admission to the hospital in patients with suspected uremic pancreatitis and destructive pancreatitis, the concentrations of β2-microglobulin and macroglobulin are determined serum, and then the ratio coefficient is calculated according to the formula K = β2M / MG × 100, where β2M is the concentration of β2-microglobulin, mg / l, MG is the concentration of macroglobulin, mg / l, and if K is less than 1, destructive pancreatitis is diagnosed, and if K is more than 1, uremic pancreatitis is diagnosed.