RU2429487C1 - Early diagnostic technique for renal irritation in patients with rheumatoid arthritis - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: there are evaluated daily proteinuria, urine specific density in Zimnitsky's test, leukocyturia and erythrocyturia in Nechiporenko's test, glomerular filtration rate (GFR), a blood creatinine level, and also structural-morphological values by renal ultrasound. If the examined parameters are within normal fluctuations, there are additionally evaluated microalbuminuria (MAU), urine albumin/creatinine ratio urine and functional renal reserve (FRR). If the MAU value is within 0.02-0.3 g/l, the FRR value is within 14-9% and the urine albumin/creatinine ratio is 3.4 to 33.9 mg/mmol, an early stage of renal irritation is diagnosed.

EFFECT: use of the technique provides the early detection of renal irritation in patients with rheumatoid arthritis.

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Description

The invention relates to medicine, namely rheumatology, and for the early diagnosis of kidney damage in patients with rheumatoid arthritis (RA).

Rheumatoid arthritis (PA) is an autoimmune disease characterized by the development of chronic symmetric destructive polyarthritis with the involvement of many body systems in the pathological process. The development of extra-articular systemic lesions in RA largely determines the severity and prognosis of the disease (1). Kidney damage in RA occurs with a high frequency from 57 to 73% (2; 3). The course of rheumatoid nephropathy, like other chronic kidney diseases, is progressive in nature with the development of nephrosclerosis and a decrease in the base of functioning nephrons with an outcome in chronic renal failure, with an extremely unfavorable prognosis, which leads to the importance of early diagnosis of nephropathy in RA and its treatment.

In the literature there are no criteria for the early diagnosis of kidney damage in RA.

Closest to the proposed one is a method for diagnosing kidney damage in patients with RA, which consists in evaluating generally accepted laboratory tests: general urine analysis (OAM), urine tests according to Nechiporenko and Zimnitsky, daily proteinuria, bacteriological analysis of urine, blood creatinine level, glomerular filtration rate, instrumental research methods (excretory urography, dynamic nephroscintigraphy, ultrasound (ultrasound) of the kidneys, as well as data from a morphological study of kidney tissue (nephrobio psia) (4) All of the above methods for studying the diagnosis of kidney damage reveal a pathological process in the late stages, and nephrobiopsy is prescribed to rheumatological patients with marked changes in laboratory parameters, usually reflecting a far-reaching lesion of the parenchyma and renal interstitium, and is associated with a risk of complications since the procedure is invasive.

A new technical task is to increase accuracy, reproducibility, and information content.

To solve the problem in a method for early diagnosis of kidney damage in patients with RA, which consists in determining the values of daily proteinuria, specific gravity of the urine in the sample according to Zimnitsky, leukocyturia and erythrocyturia in the sample according to Nechiporenko, the values of glomerular filtration rate (GFR), blood creatinine level, and also structural and morphological parameters according to the ultrasound of the kidneys, when the parameters of the studied parameters are within the normal range, additionally determine microalbuminuria (MAU), the ratio of albumin / to urinary eatinin and functional renal reserve (PDF) and with MAU levels in the range of 0.02-0.3 g / l, PDF in the range of 14-9% and albumin / creatinine ratio in the urine from 3.4 to 33 , 9 mg / mmol diagnose an early stage of kidney damage in RA.

The method is as follows.

After verifying the diagnosis of RA in a patient with normal OAM, daily proteinuria, urine tests according to Nechiporenko and Zimnitsky, GFR, blood creatinine level, as well as after ultrasound of the kidneys, such indicators as UIA, albumin / creatinine ratio in urine and PDF are determined.

Diagnostic test strips Microalbuphan (Microalbuphan) PLIVA - Lachema Diagnostika s.r.o. are used for a semi-quantitative rapid assessment of the degree of UIA, as well as the albumin / creatinine ratio in urine. Karasek, CZ.

A patient is taken a urine sample of 30-50 ml in a clean dish without traces of detergents and disinfectants. Test urine should not stand more than 4 hours. The test strip is immersed in the test urine for 1-2 seconds so that all reagent zones are moistened. Spend a strip about the edge of the urine container or blot the strip, gently pressing the edge of the strip to a napkin to remove excess urine. Lay the napkin horizontally. After approximately 60 seconds, an assessment is made by comparing the color of the areas with the color scale on the label. To interpret the results, the albumin / creatinine coefficient is calculated.

In order to determine the FPR (5), a double sampling of blood from a vein with a volume of 5 ml is performed: the first to determine the basal creatinine level, the second to determine the creatinine level after protein loading (2 hours after stimulation). An acute oral load of protein is carried out at the rate of 1.5 g of protein per 1 kg of body weight. In the future, GFR (Cockcroft - Gault formula) is calculated (6). The value of the PDF is defined as the difference between the maximum GFR achieved 1.5-2 hours after stimulation, and the basal level of GFR. It is believed that the absence of its increase in response to protein load indicates a depletion of the lateral distribution. Normal PDF is 15% and higher.

When the UIA level is in the range of 0.02-0.3 g / l, the value of the PDF is in the range of 14-9% and the albumin / creatinine ratio in the urine is from 3.4 to 33.9 mg / mmol, an early stage of kidney damage in RA is diagnosed .

In order to develop evaluation criteria characterizing the pathological process in the kidneys in RA, we examined 50 patients aged 30 to 50 years suffering from rheumatoid arthritis, the duration of the disease was 5-10 years. Of these, 28 had a seropositive variant of RA, 22 had seronegative variant, II degree of activity, II-III X-ray stage of the disease prevailed. All patients retained nitrogen excretion function and there were no deviations in the analysis of urine, GFR, and ultrasound of the kidneys. The control group consisted of 20 healthy individuals, comparable in age and sex with the main group.

In the study of the proposed method for the early diagnosis of kidney damage in patients with RA, the following results were obtained.

In 27 (54%) of the 50 patients, an increase in urine albumin level above 0.02 g / l was noted; its average value was 0.087 ± 0.025 g / l in comparison with healthy individuals whose value was 0.014 ± 0.002 g / l (p <0.05). The number of patients with an albumin / creatinine ratio of more than 3.4 mg / mmol was 26 (52%) people, with an average value of this indicator 13.52 ± 2.76 mg / mmol, which is statistically higher than in the control group - 2.7 ± 0.2 mg / mmol (p> 0.05). In 18 (36%) patients, FPR less than 15% was recorded, averaging 8.72 ± 1.2%, FPR in the control group was preserved and its average level was 25.3 ± 2% (p <0.05) . In the control group, 2 people (10%) showed MAU, an albumin / creatinine ratio of more than 3.4 mg / mmol was also detected in 2 people (10%).

It should be noted that in patients with rheumatoid arthritis who had MAU and a urine albumin / creatinine ratio above 3.4 mg / mmol, the PDF was below 15%. In 3 patients (6%) with rheumatoid arthritis, there was only microalbuminuria with PDF above 15%. In 4 patients (8%), there was an increase in the ratio of albumin / creatinine in urine above 3.4 mg / mmol with a PDF of 15% or higher. Observation of patients with RA who had only UIA or only an increase in the albumin / creatinine ratio of urine for 2 years did not reveal significant and obvious signs of involvement in the pathological process of the kidneys, in contrast to the group of people who had UIA, the ratio of albumin / creatinine urine above 3.4 mg / mmol and a decrease in the PDF, where there was a statistically significant negative dynamics of the indicators.

In the group of healthy individuals, MAU was detected in 2 out of 20 people (10%), their urinary albumin / creatinine ratios were 3.6 and 3.8 mg / mmol, respectively, but the PDF was preserved (more than 15%). A thorough examination allowed them to exclude diabetes and cardiovascular diseases that could lead to changes in the analysis of urine.

Thus, the diagnostic criteria for early kidney damage in patients with RA can be considered indicators of the level of MAU in the range of 0.02-0.3 g / l, the value of the PDF in the range of 14-9% and the ratio of albumin / creatinine in the urine from 3.4 to 33.9 mg / mmol.

Example 1

An example of the use of the proposed method for early diagnosis of kidney damage in patients with RA can be the case history of a patient S., 48 years old, who was being treated in the rheumatology department of the TKB from September 3, 2007 to October 2, 2007 and from August 10, 2009 to August 28, 09.

During the first hospitalization:

Upon receipt of a complaint of pain in the knee, wrist joints, II-III metacarpophalangeal joints on the right, morning stiffness up to 45 minutes. Limitation of range of motion in the wrist joints.

From the anamnesis it was found out that the diagnosis of RA was made in the spring of 2005, when pains in the wrist, metacarpophalangeal, metatarsophalangeal joints and the stiffness of the morning appeared for up to 2 hours. In OAK, the acceleration of ESR to 48 mm / h was determined, in the immunological analysis of blood CRP +++, the positive value of rheumatoid factor (RF). Took Nise in the rhythm of pain, midcalm 150-300 mg per day. Hospitalization is planned for the correction of the condition, the selection of basic treatment.

With an objective examination:

Satisfactory condition, active position, clear consciousness. Body weight 69 kg, height 158 cm. Skin integument of physiological color, normal humidity. Heart sounds are clear, the rhythm is correct. HELL 130/80 mm Hg, pulse 64 per minute. The vesicular breathing, no wheezing. The abdomen is soft, painless on palpation. The liver along the edge of the costal arch, the edge is sharp even, soft, painless. The projection point of the gallbladder is painless. The kidneys are not palpable. The symptom of "striking" is negative on both sides. No swelling.

Wrist joints - moderate proliferative phenomena, painful with back and palmar flexion. II-III metacarpophalangeal joints on the right are painful on palpation, there is no edema. The knee joints are slightly painful on palpation, cold to the touch, the symptom of "running patella" is negative. The remaining groups of joints without signs of active inflammation.

The following studies have been conducted.

- General blood test: red blood cells - 3.4 · 10 ¹² / l; white blood cells - 4.5 · 10 ⁹ / l; Hb - 128 g / l; PO Box - 4%; s / i - 44%; eosinophils - 0%; monocytes - 7%; lymphocytes - 45%; basophils - 0%; ESR - 34 mm / h, platelets - 297 · 10 ⁹ / L.

- General urine analysis: color - transparent yellow; beats weight - 1017; protein - neg .; sugar - neg .; white blood cells are single in the field of view.

- Urine analysis according to Nechiporenko: white blood cells 500, red blood cells 250.

- Biochemical analysis of blood: glucose - 5.0 mmol / l; about. protein - 74 g / l; bilirubin 10.2-0.0 μmol / l; ACT - 23 u / l, ALT - 32 u / l, creatinine - 70 μmol \ l, CRP ++.

- GFR was 105 ml / min.

- Rheumatoid factor 432.5 u / ml; circulating immune complexes 124 units.

- Radiography of the hands, feet - Conclusion: signs of rheumatoid arthritis of the II-III stage.

- Ultrasound of the kidneys: Kidneys: right 95 × 47 mm; left 92 × 50 mm; contours are even, mobility is saved; right kidney - parenchyma 15 mm; left kidney - parenchyma 16 mm. The boundaries of the sinuses are clear. The cavities are not expanded. Conclusion: Ultrasound imaging of the kidneys is within normal limits.

Additionally, the following study was carried out, according to the proposed method.

- Urine albumin level of 0.03 g / l.

- Urine creatinine level 2.2 mmol / L.

- Urine albumin / creatinine ratios of 13.6 mg / mmol.

- PDF was 13%.

Based on complaints, anamnesis, objective, laboratory and instrumental studies, the diagnosis was made: Rheumatoid arthritis, seropositive, with extraarticular manifestations (rheumatoid nephropathy, initial stage), activity II, stage II-III, functional insufficiency I.

The patient was prescribed methotrexate therapy at a dose of 15 mg per week. During the observation period of two years, the patient had no signs of exacerbation of RA. However, there was a negative trend in urinalysis: proteinuria in the general urine analysis increased to 0.242 g / l, minimal erythrocyturia appeared - in the urine analysis according to Nechiporenko 4000, the GFR decreased to 80.3 ml / min, the PDF decreased to 8%, according to the DSS moderate decrease in secretory function of the kidneys.

The patient underwent nephrobiopsy to clarify the nature of kidney damage and choose the optimal management tactics. According to the results of nephrobiopsy, focal mesangiopliferative glomerulonephritis.

Summing up the observation of patient C. for two years, we can conclude that the previously diagnosed initial stage rheumatoid nephropathy was confirmed by its further course.

Thus, the use of the proposed method for early diagnosis of kidney damage in RA allows doctors to obtain accurate early diagnostic criteria for kidney damage in patients with RA, which contributes to more effective therapy and a better prognosis of the course of RA.

Information sources

1. Balabanova P.M. Rheumatoid Arthritis / P.M. Balabanova // Rheumatic diseases; under. ed. V.A. Nasonova, N.V. Bunchuka. - M.: 2000. - S.257-295.

2. Kosweki Y. A prospective study of renal disease in patients with early rheumatoid arthritis / Kosweki Y., Terai C., Moriguchi M., Uesato M., Kamatani N. // Ann Rheum Dis. - 2001. - T.60 - No. 4 - p.327-331.

3. Helin H.J. Renal biopsy findings and clinicopathologic correlations in rheumatoid arthritis / Helin H.J., Korpela M.M., Mustonen J.T., Pastemack A.I. // Arthritis Rheum. - 1995. - T.38 - No. 4 - p. 242-247.

4. Kanevskaya M.Z. To the problem of rheumatoid nephropathy / Kanevskaya M.Z., Varshavsky V.A. // Ter. archive. - 2003. - No. 5. - S.24-29 (prototype).

5. Greenstein Yu.I. Preclinical diagnosis of kidney damage in hypertension / Yu.I. Grinshtein, VV Shabalin // Ter. archive. - 2004. - No. 4. - S. 40-43.

6. Cockcroft D.W. Prediction of creatinine clearance from serum creatinine / Cockcroft D.W., Gault M.H. // Nephron. - 1976.T.16, p.31-41.

Claims (1)

A method for the early diagnosis of kidney damage in patients with rheumatoid arthritis, which consists in determining the values of daily proteinuria, specific gravity of the urine in the sample according to Zimnitsky, leukocyturia and erythrocyturia in the sample according to Nechiporenko, glomerular filtration rate (GFR), blood creatinine level, as well as structural and morphological indicators according to the ultrasound of the kidneys, characterized in that when the parameters of the studied parameters are within normal fluctuations, microalbuminuria (MAU) is additionally determined, the ratio of al urine / creatinine in the urine and functional renal reserve (PDF) and with MAU levels in the range of 0.02-0.3 g / l, the PDF in the range of 14-9% and the albumin / creatinine ratio in the urine from 3.4 up to 33.9 mg / mmol diagnose an early stage of kidney damage.