The relationship between kidney function tests and systemic lupus erythematosus.
Aim of the study
The aim of the present study was to determine the clinical utility of some biochemical parameters in the differential diagnosis of Systemic Lupus Erythematosus (SLE) patients.
Subjects and Methods
The present study was carried out on 40 SLE patients according to the criteria of American Rheumatism Association (ARA); 20 other patients with rheumatic diseases and 20 normal controls were tracked in the study. All the groups of the study were tested for complete blood picture (CBP), erythrocyte sedimentation rate (ESR), kidney function tests and total protein in plasma and urine.
The level of haemoglobin was decreased significantly in SLE, while the group with other rheumatic diseases showed non significant change as compared to the normal control. Leukopenia was common in SLE patients only. The count of white blood corpuscles decreased significantly in SLE in comparison with the normal control. The differential count of white blood corpuscles in SLE patients showed significant decrease in both lymphocytes and neutrophiles while the control group did not. ESR in different rheumatic diseases exhibited a significant increase as compared to the control group. The kidney function tests showed a significant increase in SLE patients only, while the kidney function measures in patients with other rheumatic diseases were more or less unchanged. The levels of blood urea and albumin in urine exhibited a significant increase in the SLE group.
In conclusion, we suggest the use of kidney function tests in the differential diagnosis of SLE.
Keywords: Lupus Erythematosus, Systemic Tests, Kidney function Diagnosis, Differential Complete blood count, Erythrocyte sedimentation rate
Kidney function tests
Kidney function tests (Health aspects)
Systemic lupus erythematosus (Risk factors)
Systemic lupus erythematosus (Diagnosis)
Systemic lupus erythematosus (Research)
|Author:||Soliman, Hanan A.E.|
|Publication:||Name: International Journal of Health Science Publisher: Renaissance Medical Publishing Audience: Academic Format: Magazine/Journal Subject: Health Copyright: COPYRIGHT 2009 Renaissance Medical Publishing ISSN: 1791-4299|
|Issue:||Date: Jan-March, 2009 Source Volume: 2 Source Issue: 1|
|Topic:||Event Code: 310 Science & research|
|Geographic:||Geographic Scope: Egypt Geographic Code: 7EGYP Egypt|
Systemic Lupus Erythematosus (SLE) is a chronic inflammatory disease of unknown cause, but genetic, hormonal, environmental and immunologic factors all appear to play a role. It may affect the skin, joints, kidneys and other organs of the body. (1) Kaposi (2) was the first who reported that lupus could exist as a systemic disorder and not just a skin problem. However the recognition of the lupus erythematosus(LE) cell (3) in 1948 opened the possibility that pathologic abnormalities might have an immunologic basis.
Diagnosis of SLE can be somewhat difficult. There are no definitive tests for diagnosing SLE. Many of the symptoms and laboratory test results of SLE patients are similar to those of patients with different diseases, including rheumatoid arthritis, multiple sclerosis, and various nervous system and blood disorders. When a patient diagnosed with lupus develops new or recurring symptoms, laboratory testing of blood or urine can add information on whether the symptoms are due to an increase in lupus activity. Generally the disease activity is positively correlated with a rise in: ESR, urine protein or cellular casts, kidney function tests, complete blood count (CBC) and serum albumin.
Anemia is the most common finding occurring in 50% of patients and it may reflect inflammation, renal insuficiency, blood loss and immune mechanisms. (4) Leukopenia (white blood cell count of less than 4500) has been noted in 50 to 60% of patients. Functional defects of neutrophils have also been noted in SLE patients. The number of basophils may be decreased during active SLE. (5) The electrophoretic pattern in SLE is not specific. Serum albumin levels are low and gamma globulin levels may be low in nephrotics. (6) Erythrocyte sedimentation rate (ESR) was elevated in patients with active disease.
Lupus nephritis(LN) is the most common and serious manifestation of Systemic lupus erythematosus. The World Health Organization (WHO), the International Society of Nephrology and the Renal Pathology Society classification (2003) tend to correlate LN with the clinical syndrome of SLE and provide valuable information regarding prognosis and guidelines for treatment. (7) The interpretation of all these tests and their connection with symptoms can be difficult to prove.
Rheumatoid arthritis (RA) is a chronic, inflammatory disorder of unknown etiology characterized by the manner in which it involves joints. (8) Progressive systemic sclerosis (PSS) or scleroderma is a disorder of connective tissue, vascular lesions are prominent in PSS and are responsible for many pathological changes. (9) PSS is a disease in which many parts of the body become permanently thick and hard, and lose their ability to work properly. The most common part of the body involved is the skin. When the disease occurs only in the skin it is called scleroderma. PSS may also affect the joints, muscles, blood vessels, and the kidneys. The course and severity of the disease varies greatly among patients. PSS often gets worse over time. Polymyostis (PM) is an inflammatory disease of skeletal muscle characterized by muscle weakness and elevated serum levels of muscle enzymes. (10) Ankylosing spondylos (AS) is a chronic inflammatory disorder which includes pain and tenderness in the joints and spasm of the para vertebral muscles. (11) Mixed Connective Tissue disease (MCTD) is a mixture of clinical features found in RA, PSS, PM and AS. (12)
SUBJECTS AND METHODS
The present study was carried out on patients diagnosed clinically at the Rheumatology Unit, Birmingham University, UK.
Group I-Normal Controls
Twenty normal persons(10 females and 10 males) with no previous history of any rheumatic pains and receiving no treatment, were tracked as controls, and their ages ranged from 20-45 years.
Group II-SLE patients
Fourty patients (32 females and 8 males) with systemic lupus erythematosus (SLE) fulfilling the American Rheumatism Association (ARA) revised criteria for the classification of SLE. (13) Their ages ranged from 11-45 years.
Group III-Other rheumatic diseases
Twenty patients with other rheumatic diseases:
1) Four patients with rheumatoid arthritis, two females and two males, fulfilling the Revised ARA criteria for classification of RA8, aged from 20-55 years.
2) Four females with mixed connective tissue disease (MCTD), aged from 20--40 years with the criteria for systemic lupus erythematosus, rheumatoid arthritis, progressive systemic sclerosis, and polymyositis /dermatomyositis.
3) Four patients with progressive systemic sclerosis(PSS) fulfilling the ARA criteria for classification of PSS. (9) All patients were females with age ranging from 18-30 years.
4) Four patients with polymyositis (PM),their ages ranged from 10-35 years fulfilling the criteria. (14)
5) Four patients with ankylosing spondylitis (AS), their ages ranged from 17-30 years fulfilling the New York criteria for AS. (15)
From each individual, blood samples and 24-hour urine samples were collected.
Blood samples were collected from healthy controls and patients, and were tested freshly for the following assessments:
Complete Blood Picture(CBP)
It was assayed according to the method of Instructions for Blood picture, Coultronics France, S.A.
Erythrocyte Sedimentation Rate(ESR)
The method was assayed according to the method of Westergren. (16)
II-Kidney function tests
It was detected according to the method of Fawcett and Scott (17) and cited by Varley. (18)
It was assayed by the method of Brod and Sirota (19) and cited by Varley. (18)
Serum Uric Acid
It was assayed by the method of Caraway. (20)
Protein in urine
It was assayed by Henery et al. (21)
It was assayed according to Wootton. (22)
It was assayed according to the method of Tietz. (23)
From the result shown in fig.1, it is quite apparent that patients with SLE and other rheumatic diseases such as rheumatoid arthritis (RA), mixed connective tissue disease (MCTD), progressive systemic sclerosis (PSS) exhibited a significant decrease in the haemoglobin content compared to normal control (P< 0.001 for each, except RA P < 0.05), while in the other rheumatic diseases [Polymyositis (PM), ankylosing spondylitis (AS)], its level did not show any significant changes.
The total white blood corpuscles showed a slight decrease in patients with SLE disease and statistical significant increase in patients with RA disease (P< 0.05 for both). The differential count of white blood corpuscles in SLE patients showed significant decrease in both lymphocytes and neutrophils (P< 0.01 and 0.05, respectively). While in the RA disease, the percentage of neutrophils showed marked increase as compared to the normal controls (P<0.01). On the other hand, the total white blood corpuscles and its differential in patients with the other rheumatic diseases (such as MCTD, PSS, PM and AS) were more or less unchanged.
Figure 2 shows that patients with different rheumatic diseases exhibited a significant increase in the levels of ESR comparing with the normal control group. The kidney function tests (urea, uric acid, creatinine, creatinine clearance and 24-hour urinary albumin excretion), showed a significant increase in its levels in SLE patients (P<0.001 for each parameter) as compared to normal controls. On the other hand, the kidney function tests in patients with other rheumatic diseases were more or less unchanged, except in PSS, where the levels of blood urea and albumin in urine, exhibited a significant increase (P< 0.01 and 0.001, respectively) (See Figure 3).
The separation of the serum total proteins in SLE patients and other rheumatic diseases (Fig.4) showed that there was a significant decrease of serum albumin in SLE, RA and PSS patients in comparison with normal controls (P<0.001 for each), while in other rheumatic diseases (MCTD, PM, and AS) its level did not show any significant changes. In the studied rheumatic diseases, a1-globulin did not show any statistical changes (except in PSS where it showed a statistical increase, P< 0.01), [+ or -]2-globulin was increased significantly in SLE, RA, MCTD, PSS patients (P< 0.001 for each, except in PSS patients P< 0.01) comparing with the normal control group. While the PM and AS diseases did not show any significant changes in the serum level of [+ or -]2-globulin. The level of [beta]-globulin in all rheumatic diseases was more or less within the normal range, while the level of [gamma]-globulin showed a significant increase in all rheumatic diseases (SLE, RA, MCTD, PSS, PM) with statistical significant P<0.001 for each except AS.
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The present study was carried out to determine the clinical utility of some parameters in the differential diagnosis of SLE patients and also to suggest the possibility of adding them as a new criterion, in addition to the American Rheumatism Association (ARA) criteria (1982), which can establish the diagnosis on rigid grounds.
The decrease of haemoglobin level in SLE is believed to be due to bone marrow depression resulting from kidney involvement. This is in harmony with the view of Bauer (24) who reported that a mild to moderate normochromic microcytic anemia is seen in almost every patient with SLE. It can be classified as an anemia of chronic disorders, since both the serum iron concentration and the total iron binding capacity are low. Other authors (25) stated that a mild anemia may happen in PSS, which may have an iron-deficient component, usually normochromic and normocytic and hemolytic only if the microangiopathic anemia of hypertension and /or renal failure is present, and thought to be due to gastrointestinal blood loss, while in MCTD they found moderate anemia in 30-40% of cases. (12) This constancy may be explained by the results of some authors (26) who found that functional defects of neutrophils have been noted in SLE patients and are thought to usually reflect serologic immune abnormalities (i.e. immune complexes, complement activation) or medications (i.e. glucocorticoids).
In the presence of inflammation anywhere in the body, the liver rapidly increases its synthesis of fibrinogen, resulting in an elevated ESR. Alpha globulins, and to lesser extent gamma globulins, also rise with similar results. (6) ESR in different studied rheumatic diseases exhibited a significant increase compared to the control group. Yazici et al (27) demonstrated that the degree of morning stiffness appears to reflect functional disability and pain more than traditional markers of inflammation such as joint counts and ESR in patients with early RA. The inclusion of morning stiffness as a marker of inflammatory activity in classification criteria for RA, was suggested in most clinical trials for RA.
The kidney function tests showed a significant increase in its level in SLE patients as compared to normal controls. On the other hand, the kidney function tests in patients with the other rheumatic diseases were more or less unchanged except in PSS. Godfrey et al (28) demonstrated that significal number of SLE patients may be missed if biochemical creatinine clearance or serum creatinine concentration alone is used to assess renal disease. Other researchers (29) found that SLE alone develop glomerulonephritis leading to renal disease which most commonly presents with nephrotic syndrome. Karstila et al (19) detected statistically significant differences between the correlation of plasma creatinine and glomerular filtration rate (GFR) of rheumatic diseases.
The levels of blood urea and albumin in urine exhibited a significant increase as compared to normal controls. Fiehn et al (30) found that albumin appears to be taken up by peripheral blood cells in rheumatic disease. Wunder (31) found that the albumin appears to be a suitable drug carrier in RA, most likely due to effects on synovial fibroblasts.
This hypoalbuminemia presented in SLE and PSS is due to the renal affection and the increased albumin breakdown as a part of the general hypermetabolic state in proportion to the activity of the RA, as reported by Faye et al. (11) It has been found that the presence of acute inflammation may be reflected by an increase in the a2-globulins and a more chronic inflammatory process by a polyclonal increase in immunoglobulins. Elevations of B-globulins are sometimes seen in cases with acute inflammation but may be also increased independently of inflammation. (6)
In conclusion we suggest that the use of the kidney function tests are useful and help the differential diagnosis of rheumatic diseases.
Conflict of interest: None
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Hanan A.E. Soliman
Chemistry Department, Biochemistry Branch, Faculty of Science, Beni--Suef University, Egypt
Corresponding author: Hanan A.E. Soliman, Department of Chemistry, Biochemistry Branch, Faculty of Science, University of Beni-Suef, Beni-Suef, Egypt.
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