Serum Renalase Level as A Marker of Activity and Severity in Lupus Nephritis Cases (original) (raw)
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Renalase and lupus nephritis: disease activity and histopathological classification
Egyptian Rheumatology and Rehabilitation, 2018
Aim To measure the level of serum renalase and to clarify its relation to lupus nephritis (LN) activity and histopathological classification. Patients and methods This study was carried out on 40 patients with systemic lupus erythematosus (SLE), diagnosed according to systemic lupus international collaborating clinics classification criteria (SLICC) criteria, and 20 healthy controls. They were 20 patients without nephritis and 20 patients with LN (17 active and three inactive LN). Venous blood samples were taken from all participants for complete blood count, erythrocyte sedimentation rate, kidney function, anti-double-stranded DNA, C3, C4, and renalase level. The serum renalase levels were determined by enzyme-linked immunosorbent assay. Assessments of protein in 24-h urine collection and protein/creatinine (P/C) ratio were done. Renal biopsies were obtained from patients with LN, with staging and activity and chronicity indices assessment. SLE disease activity was measured by Systemic Lupus Erythematosus Disease Activity Index, and LN activity was estimated by renal Systemic Lupus Erythematosus Disease Activity Index. Results Renalase levels were higher in patients with LN than both patients with SLE without LN and control group. The serum renalase levels of patients with LN were positively correlated with P/C ratio, 24-h proteinuria and C3, but negatively correlated with Systemic Lupus Erythematosus Disease Activity Index. For patients with active LN, there was no significant correlation between their serum renalase levels and the indicators of renal activity, including erythrocyte sedimentation rate, proteinuria, P/C ratio, anti-double-stranded DNA, C3, C4, and activity index of renal biopsy. The median of renalase as a marker for diagnosis of LN was 134.65, with a cutoff value of 100 μg/ml. Conclusion Serum renalase may be involved in LN pathogenesis but was not a good predictor for either LN activity or various stages of LN histopathology.
Serum Renalase Levels Correlate with Disease Activity in Lupus Nephritis
PloS one, 2015
Lupus nephritis (LN) is among the most serious complications of systemic lupus erythematosus (SLE), which causes significant morbidity and mortality. Renalase is a novel, kidney-secreted cytokine-like protein that promotes cell survival. Here, we aimed to investigate the relationship of serum renalase levels with LN and its role in the disease progression of LN. For this cross-sectional study, 67 LN patients and 35 healthy controls were enrolled. Seventeen active LN patients who received standard therapies were followed up for six months. Disease activity was determined by the SLE Disease Activity-2000 (SLEDAI-2K) scoring system and serum renalase amounts were determined by ELISA. Predictive value of renalase for disease activity was assessed. Furthermore, the expression of renalase in the kidneys of patients and macrophage infiltration was assessed by immunohistochemistry. Serum renalase amounts were significantly higher in LN patients than in healthy controls. Moreover, patients w...
Bulletin of Egyptian Society for Physiological Sciences
Background: Systemic lupus erythematosus (SLE) is a chronic multisystem autoimmune disease characterized by complex clinical manifestations and chronic inflammatory processes with failure of immunoregulatory mechanisms. Kidney is one of the most commonly affected organs. Considering the morbidity associated with SLE and particularly with lupus nephritis (LN), it is important to identify novel biomarkers of disease activity which could aid in the detection and assessment of flares and degree of activity. At present, activity of SLE is assessed based on clinical symptoms and biochemical parameters such as autoantibody (e.g antinuclear antibody (ANA)) and serum complement. However, these biomarkers are not specific for evaluating renal activity. Renal biopsy is the gold standard for assessment of kidney damage and disease activity, but its usage is restricted as it is an invasive procedure. Aim of the work: In the present study, plasma level of advanced oxidation protein products (AOPPs) and peripheral blood mononuclear cells nuclear factor-κB (PBMCs NF-κB) level as well as serum levels of fetuin-A, 25-hydroxyvitamin D (25OHD), calcium (Ca), inorganic phosphate were studied as novel biomarkers of LN activity and progression. Methods: The study included 30 SLE female patients, 15 without nephritis (group II) and 15 with nephritis (group III), in addition to 15 agematched healthy controls (group I). Overnight fasting blood was collected from all subjects for measurement of plasma AOPPs level, PBMCs NF-κB level and serum fetuin-A level, 25OHD level, Ca and inorganic phosphate levels as well as calculation of calcification risk index (CRI). Results: Plasma AOPPs, PBMCs NF-κB, serum inorganic phosphate levels and CRI were significantly higher in SLE patients (group II) than age-matched healthy controls (group I) (p<0.05) with the highest level in patients with LN (group III) meanwhile, serum fetuin-A and 25OHD levels were significantly lower in SLE patients than age-matched healthy controls (p<0.05) with the lowest level in LN patient group. In addition plasma AOPPs, PBMCs NF-κB levels and CRI showed significantly positive correlation meanwhile, fetuin-A and 25OHD levels showed significantly negative correlation with serum creatinine, 24 hours urinary albumin, erythrocyte sedimentation rate (ESR), C reactive protein (CRP), ANA, anti double stranded DNA (Anti-dsDNA) antibodies levels and SLE disease activity index (SLEDAI). Conclusions: In SLE patients, high PBMCs NF-κB and plasma AOPPs levels as well as CRI while low levels of fetuin-A and 25OHD were related to disease activity and progression.
Diagnostic Tools for Sensitive Estimation of Renal Function & Early Detection of Lupus Nephritis
Introduction: Systemic Lupus Erythematous (SLE) is a systemic autoimmune disease where the immune system mistakenly attacks the body cells and tissues, resulting in a state of chronic inflammation and tissue damage. SLE is characterized by unpredictable course, with periods of flares alternating with remissions. It can affect any part or body tissues, including heart, joints, skin, lungs, liver, nervous system, blood vessels, but still the kidney affection is one of the most commonly involved visceral organs in SLE. Although only approximately 50% of patients with SLE develop clinically evident renal disease, biopsy studies demonstrate some degree of renal involvement in most patients. Acute or chronic renal impairment may develop with lupus nephritis leading to acute or end stage renal disease. Early recognition and management of these cases can reduce the percentage of development of end stage renal disease among these patients to less than 5% of cases. Nephron is the functioning unit of the kidney, whose function is always effected as an early response to inflammation; this function can be evaluated through the estimation of the glomerular filtration rate (secretory function) as well as its excretory function. So searching for a more sensitive and specific indicator for early detection of disease flare or activity depends on the estimation of the nephron function. Aims of the study: The aims of the study are: to evaluate the most sensitive and accurate diagnostic tool to assess glomerular function and glomerular filtration rate (GFR) in lupus nephritis patients, in relation to clinical manifestations and laboratory indices, as a trial for early detection of lupus nephritis, to investigate whether dynamic renal 99mTechnetium Diethylene Triamine Penta Acetic Acid (99mTc-DTPA) Glomerular Filtration Rate (GFR) is a more sensitive indicator of the degree of renal involvement in lupus nephritis patients than laboratory measurement of serum creatinine level and creatinine clearance (CrCl) through estimated Glomerular Filtration Rate (eGFR) formulae, and to assess renal morphology by static renal 99mTechnetium Di-Mercapto Succinic Acid (99mTc-DMSA), as well as split function of both kidneys in view of renal ultrasonography (U/S). Patients & Methods: Twenty-eight patients with biopsy-proven lupus nephritis selected according to WHO classification for renal staging. The disease activity was recorded using Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) to detect active disease requiring increased treatment for activity. Immunological profiles, including ANA, anti-dsDNA, complement levels (C3, C4) were assessed. Kidney function tests, including serum creatinine, blood urea nitrogen (BUN), creatinine clearance (CrCl), glomerular filtration rate (GFR) using Cockcroft– Gault (CG),the 4-variable abbreviated Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration Formula (CKD-EPI) method, urinalysis with microscopy, 24 hours urinary proteins, as well as total serum proteins and serum albumin were measured. Dynamic 99mTechnetium labeled with Diehtylene Triamine Penta Acetic Acid (99mTc-DTPA) radioisotope renal scan was done for all patients as a part of assessment of renal GFR in all patients in the study group. Another static study was done using 99mTechnetium Di-Mercapto Succinic Acid (99mTc DMSA) to assess the morphological status as well as the split function of both kidneys in view of renal ultrasonography. Results: This study was carried out on 28 patients: 9 males (32.1%) and 19 females (67.9%).Their age ranged from (16-44 years) with a mean age (23.57± 9.57 years). Their height ranged from (147-169cm) with a mean height (155.14±7.97) and weight ranged from (37-84.5 kg) with a mean weight (59.66±16.69). As regards the renal histopathology results, 4 patients (14.28%) had mesangial glomerulonephritis, 15 patients (53.57%) had focal proliferative glomerulonephritis, 6 patients (21.42%) had diffuse proliferative glomerulonephritis, and 3 patients (10.71%) had membranous glomerulonephritis. In patients with impaired renal function the 99mTc-DTPA GFR values and C-G estimated GFR values was decreased significantly with P value <0.05, however, that GFR values obtained by the C-G estimated formula showed a total bias (– 15 ml/min/1.73m2) and relative bias (-21%). Whereas, the estimated GFR obtained by MDRD, and CKD-EPI equations are still markedly underestimating the GFR values, among the same group of patients with total bias (-28 &-26 ml/min/1.73m2) and relative bias (-40% &-37%) respectively. MDRD as well as CKD-EPI equations for estimation of GFR tend to underestimate the GFR value among patients with impaired renal functions. In the patients group with preserved (normal or near normal renal function) the measured GFR by 99mTc-DTPA dynamic renal scintigraphy showed a comparable results to that obtained from the C-G equations total bias (-5 ml/min/1.73m2) and relative bias (-5%), whereas, the GFR values are much higher in equations of MDRD, and CKD-EPI with a total bias (+5 & + 10 ml/min/1.73m2) and a relative bias (+5% & +10%) respectively. MDRD as well as CKD-EPI equations for estimation of GFR tend to overestimate the GFR value among patients with normal or near normal renal functions. There was a significant decrease in the 99mTc-DTPA measured GFR value among patients with stage III and stage IV glomerulonephritis, with a P value < 0.05, Whereas, the GFR values obtained by the C-G formula showed significant decrease only among patients with stage IV glomerulonephritis (P value = 0.016). On the other hand, (MDRD & CKD-EPI formulae) showed insignificant decreased GFR values among patients with stage III & stage IV glomerulonephritis, but they showed significantly increased GFR values among patients with stage II & stage V glomerulonephritis. Conclusion: 99mTc-DTPA as a glomerular agent provides a sensitive, physiological, reliable, accurate and reproducible method for assessment of renal function throughout different disease stages in patients with confirmed diagnosis of lupus nephritis (LN), when compared to other methods evaluating renal function in these patients. It provided a proper evaluation of the nephron function, including renal blood flow condition, the secretory function of the nephrons, as well as nephron's excretory function before and after intravenous diuretics injection. Besides, 99mTc-DMSA as a tubular agent provides a sensitive morphological image of the kidney that can help in estimation of the split function of both kidneys as well as evaluation of the disease course, compared to the traditional morphological imaging modalities (renal ultrasonography). (2016). Diagnostic Tools for Sensitive Estimation of Renal Function & Early Detection of Lupus Nephritis. J. Middle East North Afr. sci, 2(2), 34-47]. (p-ISSN 2412-9763)-(e-ISSN 2412-8937). http://www.jomenas.org. 4 Keywords: Renal isotopes scan in SLE/lupus nephritis, GFR-DTPA, DMSA, early lupus nephritis.
2019
Background Renalase is a flavoprotein involved in pathomechanisms of chronic kidney disease and heart and circulatory system disorders. Secretion and way of action of this protein are still discussed. Aim of our study was to initially estimate the balance between serum and urine renalase in healthy adults and to compare obtained ratio to chronic kidney disease patients. Methods Our study involved 28 healthy volunteers and 62 patients with diagnosed chronic kidney disease in stages I to IV. Concentration of renalase in blood serum and urine was measured using enzyme-linked immunosorbent assay (ELISA) kit (Uscn Life Science, Wuhan, China). We analyzed serum-to-urine renalase proportion in both groups and evaluated the differences using Mann Whitney U-test. Results Renalase serum-to-urine ratio was significantly higher in chronic kidney disease patients in comparison with control group (1.146 and 0.177, respectively; p<0.05). Also renalase serum-to-urine/mg creatinine ratio was high...
Diagnostics
Objectives: To assess the performance of clinical and biochemical parameters in identifying renal histopathology. To assess the performance of a combination of demographic, clinical, serological and histopathological parameters in determining renal response at one year. Methods: Data of biopsy-proven (ISN/RPS—2003 criteria) Lupus Nephritis (LN) were extracted from the institute database. Demographic, clinical and biochemical parameters at the time of biopsy were noted, and their associations with histopathological class, activity and chronicity scores were evaluated. Follow-up data at one year were collected. Complete, partial or no response (CR, PR, NR) for renal outcomes at one year and the predictors of NR were assessed. Results: Out of the 333 renal biopsies, 240 (71.8%) were Class III/IV. More patients with Class III/IV LN had hypertension (52.1%) and low eGFR (p < 0.001). Among Class III/IV, AS correlated weakly with UPCR (r = 0.31, p < 0.01), eGFR (r = −0.172; p < 0....
Initial Validation of a Novel Protein Biomarker Panel for Active Pediatric Lupus Nephritis
Pediatric Research, 2009
Lupus nephritis (LN) is among the main determinants of poor prognosis in systemic lupus erythematosus (SLE). The objective of this study was to 1) isolate and identify proteins contained in the LN urinary protein signature (PS) of children with SLE; 2) assess the usefulness of the PS-proteins for detecting activity of LN over time. Using surface-enhanced or matrix assisted laser desorption/ ionization time of flight mass spectrometry, the proteins contained in the LN urinary PS were identified. They were transferrin (Tf), ceruloplasmin (Cp), α1-acid-glycoprotein (AGP), lipocalintype prostaglandin-D synthetase (L-PGDS), albumin and albumin-related fragments. Serial plasma and urine samples were analyzed using immunonephelometry or ELISA in 98 children with SLE (78% African-American) and 30 controls with juvenile idiopathic arthritis. All urinary PS-proteins were significantly higher with active versus inactive LN or in patients without LN (all p<0.005), and their combined area under the receiver operating characteristic curve was 0.85. As early as 3 months before a clinical diagnosis of worsening LN, significant increases of urinary Tf, AGP (both p < 0.0001) and L-PGDS (p < 0.01) occurred, indicating that these PS-proteins are biomarkers of LN activity and may help anticipate the future course of LN.
Renal function assessment in patients with systemic lupus erythematosus
Rheumatology International
Few studies have evaluated the glomerular filtration rate (GFR) in patients with systemic lupus erythematosus (SLE). Even though the National Kidney Foundation (NKF) suggests using the equations to estimate GFR, rheumatologists continue using creatinine clearance (CCl). The main objective of our study was the assessment of different equations to estimate GFR in patients with SLE: Simplified MDRD study equation (sMDRD), CCl, Cockcroft Gault (CG), CG calculated with ideal weight (CGi), Mayo Clinic Quadratic (MCQ), and Chronic Kidney Disease Epidemiology Collaboration Equation (CKD-EPI). CKD-EPI was considered as the reference standard, and it was compared with the other equations to evaluate bias, correlation (r), sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), percentage of measurement of GFR between 70–130% of GFR measured through CKD-EPI (P30) and to compute the ROC curves. Adequacy of the 24-h urine collection was evaluated. To classify patients into GFR < 60 ml/min/1.73 m2, the best sensitivity and NVP were obtained with sMDRD: the best PPV and specificity with MCQ. P30 was 99.3% with sMDRD, 77.5% CCl, 91.7% CG, 96.7% CGi, and 77.2% with MCQ. The lowest bias was for sMDRD and the highest for CCl. Only 159 (52.6%) urine collections were considered adequate, and when these patients were re-evaluated, the statistical results improved for CCl. CGi was better in general than CG. CCl should not be considered as an adequate GFR estimation. Ideal weight is better than real weight to calculate GFR through CG in patients with SLE.
Acta medica Indonesiana, 2018
BACKGROUND proliferative lupus nephritis (LN) has higher prevalence and worse prognosis than non-proliferative LN. Renal biopsy plays an important role in diagnosis and therapy of LN, but there are some obstacles in its implementation. A diagnostic scoring system for proliferative LN is necessary, especially for cases in which renal biopsy cannot be performed. This study aimed to develop a diagnostic scoring system of proliferative LN based on its diagnostic determinants including hypertension, proteinuria, hematuria, eGFR, anti-dsDNA antibody, and C3 levels. METHODS a cross-sectional study with total sampling method was conducted. Our subjects were adult LN patients who underwent renal biopsy in Cipto Mangunkusumo Hospital between January 2007 and June 2017. RESULTS from a total of 191 subjects with biopsy-proven LN in this study, we found a proportion of proliferative LN of 74.8%. There were 113 subjects included for analysis of proliferative LN determinants. The multivariate anal...