Method of estimating efficiency of treating ischemic nephropathy in newborns

FIELD: medicine.

SUBSTANCE: in order to estimate efficiency of treating ischemic nephropathy in newborn babies in early neonatal period activity of gamma-glutamyltransferase and cholinesterase in child's urine is determined in dynamics of treatment. If activity of said enzymes decreases with respect to initial level, treatment is estimated as efficient, if activity increases or does not change - as inefficient.

EFFECT: application of method makes it possible to increase accuracy of estimation of ischemic nephropathy treatment in newborns, carry out correction of therapeutic measures in due time and improve disease outcome.

1 tbl, 3 ex

 

The invention relates to medicine, namely to Pediatrics and neonatology, and can be used to assess the effectiveness of treatment of ischemic nephropathy in newborn infants in the early neonatal period.

The relevance of the method development is determined by a high frequency of ischemic nephropathy in newborns in critical condition (95,6%) [1]. When this pathology is observed relatively high mortality. Also ischemic nephropathy affects the course of other diseases in children and largely determines the outcome of these diseases [2]. One of the reasons for adverse outcomes in neonates with ischemic nephropathy is the lack of rapid, accurate and objective means of assessing the effectiveness of the treatment. A method was developed to evaluate the effectiveness of treatment of newborns will allow you to assign adequate therapy and to prevent serious consequences of ischemic nephropathy.

There is a method of evaluating the effectiveness of treatment of newborns with ischemic nephropathy by studies of renal blood flow at 1, 3, 5 and 7 day life method dopplerography on the basis of a study of time-averaged maximum velocity (CAMH) and end diastolic velocity (Ved) in the renal artery [Baibarina E.N., Burkova A.S., Evteeva NV Acute renal failure in neonates: standards for automotive technician the sticks and treatment: a Handbook for physicians. - M., 2000. - 30 S.].

The disadvantages of the method.

1. For the implementation of this method requires the involvement of a doctor of functional diagnostics with special skills.

2. Used expensive equipment.

3. The accuracy of determining time-averaged maximum velocity and end diastolic velocity in the renal artery depends on the angle of insanely, and if you incorrectly install the sensor potential measurement errors.

4. Strict adherence to conditions survey calm the child, which is difficult to achieve.

5. There is no complete correspondence between the severity of renal blood flow and pathological changes in the kidney.

6. The accuracy of the method is not known.

The closest technical solution is the method of evaluating the efficiency of treatment of ischemic nephropathy in newborns by determining the concentration of creatinine and urea in the peripheral blood of newborns in the dynamics of treatment. When the decrease of creatinine and urea relative to the original level in excess of the norm, the treatment is assessed as effective, and in the absence of a decrease or increase of its concentration as ineffective [Baibarina E.N. Violations of kidney function in critically ill newborns: author. Diss.... MD), 1999. - 33 S.].

nedostatki method.

1. Changes in the concentration of creatinine and urea may be associated not only with renal pathology.

2. Lower creatinine level is incompatible with the recovery of kidney function, and a little behind.

3. The method is invasive and traumatic.

4. Requires sampling of venous blood.

5. The accuracy of the method is not known.

These drawbacks are proposed to be eliminated in the present method.

The technical solution of the proposed method is achieved by defining in the dynamics of treatment in the urine activity of gamma-glutamyltransferase and cholinesterase. When reducing the activity of these enzymes with respect to the initial level of treatment is assessed as effective, and with increasing or unchange their activity as ineffective. The accuracy of the method 90,5%, sensitivity - 88,2%, specificity 92%.

The novelty of the method

For the first time are encouraged to evaluate the effectiveness of treatment of ischemic nephropathy in newborns by defining in the dynamics of treatment in the urine activity of gamma-glutamyltransferase and cholinesterase.

Cholinesterase is an enzyme belonging to the group of esterases [3]. Cholinesterase is a lysosomal enzyme of the kidney cells. Gamma-glutamyltransferase is an enzyme of the proximal nephron, is localized in the brush border and the membrane of the endoplasmic reticulum [4]. In the Orme in the urine contains small amounts of these enzymes (gamma-glutamyltransferase - 57,47±1,17, cholinesterase - 7,55±0,61). Increased gamma-glutamyltransferase identified in chronic glomerulonephritis, stroke rejection of the transplant kidney in adults [4]. The study of the activity of gamma-glutamyl transferase in ischemic nephropathy was not conducted.

Found increased activity of cholinesterase in the urine of newborns with expanded clinical pyelonephritis, acute interstitial nephritis, heart attack, kidney failure, glomerulonephritis, acute renal failure in newborns [5] in the late neonatal period.

However, the study of the activity of enzymes of urine in newborns during the first 5 days of life were not conducted, and it was at this time developing ischemic nephropathy. Dynamics of activity of enzymes in urine in early neonatal period has not been investigated. Effective treatment stops the effects of damaging factors on renal tissue and the activity of enzymes in the urine is reduced.

Distinctive features of the method.

It is proposed to evaluate the effectiveness of treatment of ischemic nephropathy in newborns by determining in the urine activity of gamma-glutamyltransferase and cholinesterase. When reducing the activity of these enzymes with respect to the initial level of treatment is assessed as effective, and with increasing or unchange their activity - as effectivnoe.

The method is:

1. Newborns in the dynamics of charge a one-time portion of the day. Centrifuged urine for 15 minutes at 4000 rpm to remove the formed elements and the urinary sediment;

2. For determining the activity of cholinesterase used kinetic photometric test, optimized in accordance with the recommendations of DGKS (German society of clinical chemistry) [6] with a set of reagents for determination of cholinesterase company DiaSys, Germany.

3. To determine the activity of gamma-glutamyltransferase used method of Seitz/Persicina, standardized in accordance with IFCC [7] with a set of reagents for determination of gamma-glutamyl transferase firm Biocon, Germany.

4. The results of the activity of cholinesterase and gamma-glutamyl transferase count on 1 mg allocated with urine creatinine, the result is expressed in IU/mg creatinine.

The essence of the proposed method is illustrated by the following examples.

Example 1. Baby M, from mother to 29 years, suffering from chronic pyelonephritis. Pregnancy III, proceeded against the background of nephropathy II degree, chronic intrauterine hypoxia, placental insufficiency. Delivery II, 40 weeks. Amniotic fluid is green in color with a unpleasant smell. Birth weight of 3000 g, the estimation on Apgar scale 3-5 points. the C of a generic unit, the child was transferred to the neonatal intensive care unit of children.

On the first day of life, the child was diagnosed with cerebral ischemia III severity, intraventricular hemorrhage II degree of bilateral, depression syndrome. Congenital bilateral pneumonia viral-bacterial.

Had clinical symptoms in the form of oliguria and proteinuria (protein - 0,99 g/l), edematous syndrome first degree. Urinary syndrome in the form of cylindruria. In the prototype method for biochemical analysis of blood creatinine level was 163 µmol/l, urea - 16.0 mmol/L. When dopplerography of the renal arteries was detected "pendulum-like" nature of blood flow. Diagnosed with ischemic nephropathy III degree. He was appointed standard intensive therapy (infusion therapy, therapy improves renal blood flow - dopamine).

During the examination of the newborn in the 1st days of life by the claimed method was determined cholinesterase activity, equal to 10.6 IU/mg creatinine, the activity of gamma-glutamyl transferase, equal 145,9 IU/mg creatinine.

After 2 days, in the dynamics of treatment, re-defined the activity of cholinesterase, equal 6,89 IU/mg creatinine, the activity of gamma-glutamyl transferase, equal 90,28 IU/mg creatinine, which allowed us to draw the conclusion about quite effective treatment.

In the method prototype also conducted repeated determination of creatinine, much the guilt in the blood. He was 163,5 µmol/l creatinine, 16.0 mmol/l urea, which is considered to be ineffective treatment.

The next day of an infant's life were marked decrease swelling up to a total pastoznost, normalization of diuresis, urinary syndrome characterized by proteinuria (protein - 0,033 g/l). When dopplerography of the renal arteries the blood flow in the renal arteries at the lower limit of normal.

Thus, evaluation of the effectiveness of the treatment by the proposed method was confirmed.

Example 2. Child, mother 23 years. Pregnancy proceeded against the background of hypertension, complicated co-eclampsia (nephropathy III), placental insufficiency. Delivery at 38 weeks. Amniotic fluid is green in color with a unpleasant smell. Birth weight of 3500 g, estimation on Apgar scale 3-4 points. From the generic block the child was transferred to the neonatal intensive care unit of children.

On the first day of life, the child was diagnosed with cerebral ischemia II severity, high fatty acids of II degree bilateral convulsive syndrome. Aspiration pneumonia.

Had clinical symptoms in the form of oliguria and proteinuria (protein - 0,165 g/l), edematous syndrome II. Urinary syndrome in the form of cylindruria. In the prototype method for biochemical analysis of blood creatinine level was 187 μmol/l, urea - 15.0 mmol/L. When doppleron is the philosophy of the renal arteries was detected zero diastolic blood flow. Diagnosed with ischemic nephropathy III degree. He was appointed standard intensive therapy.

During the examination of the newborn in the 1st days of life by the claimed method was determined cholinesterase activity, equal to 8.9 IU/mg creatinine, the activity of gamma-glutamyl transferase, equal to 127.9 IU/mg creatinine.

After 2 days, in the dynamics of treatment, re-defined cholinesterase activity, equal to 12.3 IU/mg creatinine, the activity of gamma-glutamyl transferase, equal 147,9 IU/mg creatinine, which allowed us to draw the conclusion about the lack of effective treatment.

In the method prototype is also re-estimation of creatinine and urea in the blood. He was 183 μmol/l creatinine, 13,0 mmol/l urea, which gave the opportunity to evaluate the treatment as effective.

However, the next day of life the child pointed to the increasing edema generalized to continued oliguria and proteinuria (protein - 0,99 g/l). When dopplerography of the renal arteries "pendulum-like" nature of blood flow. Was adjusted treatment: assigned diuretics, drugs that improve microcirculation.

After another 2 days defined cholinesterase activity, equal to 9.3 IU/mg creatinine, the activity of gamma-glutamyl transferase, 115.9 IU/mg creatinine, which gave the opportunity to evaluate the treatment as effective.

On the next day was a decrease swelling up to a total pastoznost, normalization of urine output.

Thus, evaluation of the effectiveness of the treatment by the proposed method was confirmed.

Example 3. Child D, mother 20 years, suffering from obesity II. The pregnancy was complicated in the first trimester by the threat of termination, and in the second trimester late co-eclampsia (nephropathy first degree). Delivery at 40 weeks was complicated by antepartum rupture of amniotic fluid, prolonged dry period, the persistent weakness of patrimonial activity, about which transaction caesarean section. Estimation on Apgar scale 3-5 points. On the first day of life, the child was diagnosed with cerebral ischemia II-III degree, high fatty acids of II degree left, hypertensive syndrome, increased convulsive readiness. Congenital bilateral pneumonia viral-bacterial. According to the severity of neurological symptoms, the child was transferred to the neonatal intensive care unit of children.

On the first day of life the child was a clinic in the form of moderate oliguria and proteinuria (protein - 0.33 g/l), edema syndrome of the I degree. When dopplerography of the renal arteries reduce blood flow in the left renal artery. The creatinine level in the blood was 147 µmol/l, urea - 10.0 mmol/L. diagnosed with ischemic nephropathy II degree. He was appointed standard intensive therapy.

During the examination of the newborn in the 1st with the weave of life by the claimed method was determined cholinesterase activity, is 7.9 IU/mg creatinine, the activity of gamma-glutamyl transferase, equal to 131, 5mm IU/mg creatinine.

After 2 days re-defined cholinesterase activity, equal to 8.0 IU/mg creatinine, the activity of gamma-glutamyl transferase, equal to 131, 5mm IU/mg creatinine, which allowed to give opinion on ineffective treatment.

In the method prototype is also re-estimation of creatinine and urea in the blood. He was 148,9 µmol/l creatinine, urea - 10.5 mmol/l, which gave the opportunity to evaluate treatment as ineffective.

Indeed, on the following day in the life of the child pointed to the increasing edema syndrome, remained oliguria and proteinuria (protein - 0,99 g/l). When dopplerography of the renal arteries reduce blood flow on both renal arteries. Was adjusted treatment.

After another 2 days defined cholinesterase activity, equal to 7.3 IU/mg creatinine, the activity of gamma-glutamyl transferase, equal 116,0 IU/mg creatinine, which gave the opportunity to evaluate the treatment as effective.

The next day was a decrease swelling up to a total pastoznost, normalization of urine output.

Thus, the conclusion about the effectiveness of the treatment by the proposed method was confirmed.

Advantages of the method.

1. Allows you to make timely adjustments in treatment and improve outcomes in ischemic who nephropathy in newborn infants.

2. The method is non-invasive, retraumatized.

4. Research can be conducted at any time of the day.

5. The proposed method has high accuracy - 90,5%.

In this way were examined 42 newborn child with ischemic nephropathy in the early neonatal period, 17 in the dynamics of treatment enzyme activity decreased in clinically noted improvement in 15 children; 25 children in the dynamics of treatment enzyme activity increased or not changed, 23 of them were clinically observed deterioration and was adjusted treatment.

Table
IndicatorsThe number of surveyed claimed method
All newborns42
True-positive result15
False-positive result2
A true-negative result23
A false-negative result2

- The accuracy of the proposed method: 90,5%.

The sensitivity of the proposed method: 88,2%

The specificity of the proposed method: 92,0%.

LITERATURE

1. Baibarina E.N., Burkova A.S., Evteeva NV Acute renal failure in neonates: standards for diagnosis and treatment: a Handbook for physicians. - M., 2000. - 30 S.

2. Baibarina E.N. Violations of kidney function in critically ill newborns: author. Diss... MD - M., 1999. - 33 S.

3. The Wilkinson D. Principles and methods of diagnostic Enzymology. - M., 1981. - 624 S.

4. Namazova O.S Study of enzymes of urine in the diagnosis of lesions of the kidney // Pediatrics. - 1996. No. 3. - S-86.

5. Chugunova O.L., Verbitsky V. Modern methods of laboratory diagnosis of renal pathology in the newborn // the Children's hospital. - 2001. No. 1. - P.16-20.

6. Recommendation of the German Society for Clinical Chemistry. Standardization of methods for the estimation of enzyme activities in biological fluids: Standard method for determination of cholinesterase activity // Clin. Chem., Clin. Biochem. - 1992. - Vol.30. - P.163-170.

7. Persijn JP, Van der Silk W.A. New method for the determination of gamma-glutamyltrasferase in serum // Clin. Chem., Clin. Biochem. - 1976. - Vol.14. - P.421-427.

A method of evaluating the effectiveness of treatment of ischemic nephropathy in newborns by exploring the biological material in the dynamics of treatment, characterized in that the urine of the child determine the activity of gamma-glutamyltransferase and cholinesterase, and by reducing their activity relative to the baseline treatment is assessed as effective, and when is the improving or not the change of activity - as ineffective.



 

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