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European Journal of Applied Sciences – Vol. 9, No. 5
Publication Date: October 25, 2021
DOI:10.14738/aivp.95.10983. Elsayed, Y. A. E., Zaky, K. A., Abideen, K. A., & Abozeid, A. A. (2021). Serum Renalase Level as a Marker of Activity and Severity in
Lupus Nephritis Cases. European Journal of Applied Sciences, 9(5). 289-298.
Services for Science and Education – United Kingdom
Serum Renalase Level as a Marker of Activity and Severity in
Lupus Nephritis Cases
Yasser A. Elmotaleb Elsayed
Department of Rheumatology and Rehabilitation
Faculty of Medicine, Al-Azhar University Cairo, Egypt
Khaled A. Zaky
Department of Rheumatology and Rehabilitation
Faculty of Medicine, Al-Azhar University Cairo, Egypt
Khaled A. Abideen
Department of Rheumatology and Rehabilitation
Faculty of Medicine, Al-Azhar University Cairo, Egypt
Ahmed A. Abozeid
Department of Clinical Pathology
Faculty of Medicine, Al-Azhar University, Cairo, Egypt
ABSTRACT
Introduction: Lupus nephritis (LN) is a substantial risk factor for death and
morbidity in patients with Systemic Lupus Erythematosus (SLE) (SLE). Despite
excellent immunosuppressive therapy, it nevertheless leads to a disproportionate
percentage of persons developing chronic kidney disease (CKD) or end-stage renal
disease (ESRD). Renalase is a distinctive cytokine-like protein generated by the
kidneys that promote cell survival. It has been recently linked to the etiology of LN
and may be an ideal candidate as a sensitive biomarker for flare-ups and LN
remission. Aim of the work: The purpose of this study was to evaluate the utility of
human serum renalase as a biomarker for assessing disease activity and severity in
SLE, as well as to evaluate if it can be used as a sensitive biomarker in this capacity.
Methods: This study consists of around 23 healthy controls and 46 individuals with
LN. These participants were separated into two equal groups according to disease
activity as determined by the SLEDAI (SLE Disease Activity Index): 23 cases with LN
who had disease activity and 23 cases who did not. The concentration of human
serum Renalase (RNLS) was evaluated using a very sensitive commercial enzyme
immunoassay that captures renalase from serum using (RNLS) antibody. Results:
Renalase concentrations were significantly greater in LN cases than in healthy
controls (P-value <0.001). Additionally, cases with active LN exhibited significantly
greater serum renalase concentrations than those with inactive LN (P-value
<0.005). Serum renalase concentrations were positively connected with 24-h urine
protein excretion, SLEDAI, ESR, CRP, and ds-DNA but were negatively related to
serum C3 and the class (particularly in the proliferative type) (Class III, IV, more
than class V). Conclusion: Serum renalase levels were associated with disease
symptoms in LN and may serve as a biomarker for disease activity in LN.
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European Journal of Applied Sciences (EJAS) Vol. 9, Issue 5, October-2021
Services for Science and Education – United Kingdom
INTRODUCTION
Renal disease is a severe manifestation of systemic lupus erythematosus (SLE), accounting for
a significant share of death and morbidity (1). Up to 90% of persons with SLE will have
pathologic indications of kidney damage at the time of biopsy, even though only 50% will
develop clinically serious nephritis (2). Lupus nephritis manifests clinically in a number of
different ways, from asymptomatic hematuria and/or proteinuria to a full-blown nephrotic
syndrome to a rapidly increasing glomerulonephritis with accelerating renal dysfunction.
Although there are exceptions, lupus nephritis normally improves within the first 36 months of
the disorder. Thus, screening for nephritis on a monthly basis is crucial for the continuous
evaluation and therapy of cases with SLE (3).
Current laboratory markers for lupus nephritis, such as urine protein-to-creatinine ratio,
proteinuria, anti-dsDNA, creatinine levels, and complement levels, are insufficient. Owing to a
lack of sensitivity and specificity, they are unable to distinguish between renal activity and
impairment in lupus nephritis (4).
Serum Renalase is a monoamine oxidase that can be secreted into the bloodstream by the
kidneys (5). Renalase has previously been shown to assist in regulating blood pressure by
degrading catecholamines in the bloodstream (6). Renalase treatment is associated with renal
protection and decreased macrophage infiltration in a mouse model of acute kidney injury
(AKI), showing that renalase has an anti-inflammatory role in renal dysfunction (7, 8).
The association between renalase and inflammation has been demonstrated in investigations
of organ transplantation and serum renalase concentrations in kidney and heart cases (9, 10).
The purpose of this study was to examine whether serum renalase levels were associated with
renal pathology and disease activity in lupus nephritis, to hypothesize a function for renalase
in this autoimmune and inflammatory disorder, and to assess whether it is an excellent
biomarker for lupus nephritis.
METHODS
This study included 48 patients with SLE who were evaluated through using Systemic Lupus
International Collaborating Clinics (SLICC) (2015) (11) or the New EULAR/ACR SLE
Classification Criteria 2017 (12) and 30 healthy controls. They were gathered from the
rheumatology and rehabilitation departments of the AL-Azhar University hospitals' inpatient
and outpatient clinics. The ethical council of Al-Azhar Medical School approved this study, and
all subjects were given written informed permission before participation.
All individuals with life-threatening conditions other than LN were eliminated from this
investigation (e.g., heart failure, central nervous system lupus, malignant tumor, infectious
disease), as well as those with an eGFR of less than 30ml/min/1.73 m2 or who was pregnant at
the age of 18 or 50.
On the basis of SLEDAI (SLE Disease Activity Index) ratings, the recruited cases were split into
two equal groups (13):
Group II included 23 patients of lupus with disease activity as determined by the SLEDAI.
Group III had 23 lupus patients with no signs of disease activity, as determined by the SLEDAI.
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Elsayed, Y. A. E., Zaky, K. A., Abideen, K. A., & Abozeid, A. A. (2021). Serum Renalase Level as a Marker of Activity and Severity in Lupus Nephritis
Cases. European Journal of Applied Sciences, 9(5). 289-298.
URL: http://dx.doi.org/10.14738/aivp.95.10983
The control group (Group I) consists of 23 persons who appear to be in good health and are of
comparable age and sex.
The following items were covered in a detailed examination of all participants: Complete
history taking, investigations of the general and local areas; Upon that, during the study visit,
venous blood samples were obtained by all participants in the prescribed sequence: C-reactive
protein (CRP), complete blood counting, C-reactive protein (CRP), sedimentation rate of
erythrocytes (ESR), liver-function testing, creatinine serum, uric blood urea, and serum, and
urine proteins 24-hour. To assess urinary protein excretion, 24-hour urine and spot urine
samples were obtained. Autoimmune Profile: C3 and DNA-Anti-double-strand (anti-ds-DNA- Ab) complements were evaluated by the use of an enzyme-related immune-sorbent assay
(ELISA). Renal biopsies were percutaneously collected from LN cases involved with this study
using an ultrasonographically guided biology or computed tomography needle, and
paraformaldehyde-fixed air-dry slices of the frozen LN kidney sample were delivered to the
histopathologist. Renal samples were categorized in accordance with the International Society
of Nephrology/Renal Pathology (ISN/RPS) (14).
At the study visit, serum renalase was taken, and serum was separated within three hours of
collection. To avoid repeated freeze cycles, serum was separated using Rotofix32 (Hettich- zentrifugen) at 2000x for 20 minutes and then gathered into at least four aliquots and kept at -
20°C until required for analysis. Serum renalase concentrations were determined as per the
manufacturer's procedure by an ELISA kit specific to renalase. The concentration of human
serum Renalase (RNLS) was established by a highly sensitive, commercial sandwich enzyme
immunoassay employing an (RNLS) serum renalase. This assay is very specific and sensitive for
detecting (RNLS). There was no evidence of considerable cross-reactivity or interaction
between (RNLS) and analogs (15).
The 2000 SLE Illness Activity Index (SLEDAI-2K) and Renal SLEDAI (rSLEDAI) have been used
for evaluating the activity of the disease and renal disease consecutively (13). RSLEDAI includes
haematuria, pyuria, proteinuria, and urine casts (SLEDAI-2K renal scores). Cases with LN were
divided into two categories according to their SLEDAI scores, the active LN (SLEDAI <8) and
the quiescent LN (SLEDAI <8).
STATISTICAL ANALYSIS
The Social Science Statistics Program (SPSS) version 20.0 was used to examine the data. The
standard difference and average of quantitative data were calculated (SD). Frequency and
percentage of qualitative data were used. The following tests have been performed: The
independent samples t-test of significance was used when comparing two means. A one-way
variance analysis (ANOVA) is utilized when comparing more than two means. The Chi-square
(X2) meaning test was used to examine the proportions between two qualitative parameters.
Relationships were created through Pearson's coefficient of relationship (r) test. The trust
interval was set at 95%, while the acceptable error margin was set at 5%. Therefore, the
following p-value was judged significant: The likelihood (P-value) P-value less than 0.05 was
considered important. A P-value less than 0.001 was considered to be very important. P-value
>0.05 was considered negligible.