Associations between renal deposits of complement factors, disease activity and loss of renal function in lupus nephritis

2021 ◽  
pp. jclinpath-2021-207788
Author(s):  
Jacob J E Koopman ◽  
Helmut G Rennke ◽  
Gearoid M McMahon ◽  
Sushrut S Waikar ◽  
Karen H Costenbader
Lupus ◽  
2020 ◽  
pp. 096120332097904
Author(s):  
Eman Ahmed Hafez ◽  
Sameh Abd El-mottleb Hassan ◽  
Mohammed Abdel Monem Teama ◽  
Fatma Mohammed Badr

Objective Lupus nephritis (LN) is closely associated with hyperuricemia, and uric acid is considered a risk factor for renal involvement in systemic lupus erythematosus (SLE). This study aimed to examine the association between serum uric acid (SUA) level and LN development and progression in SLE patients with normal renal function. Methods A total of 60 SLE patients with normal renal function from Ain Shams University Hospital were selected and assigned to group 1 (30 patients with LN) and group 2 (30 patients without LN). All patients were subjected to history taking, clinical examination, disease activity assessment based on SLE disease activity index (SLEDAI) and renal SLEDAI (SLEDAI-R) scores, and laboratory investigations, including as SUA, complete blood count, blood urea nitrogen (BUN), serum creatinine, creatinine clearance, urine analysis, protein/creatinine ratio, 24-h urinary protein excretion, Antinuclear antibodies (ANA), anti-dsDNA antibody, and serum complement (C3, C4). Results Disease duration, SLEDAI score, and SUA level were higher in group 1 than in group 2 (p < 0.001). SUA level was positively correlated with SLEDAI and SLEDAI-R scores, proteinuria, urinary casts, renal biopsy class, disease activity and chronicity indices, BUN level, and serum creatinine level but was negatively correlated with creatinine clearance (p < 0.05). SUA was a predictor of LN development in SLE patients (sensitivity, 83.3%; specificity, 70%). Conclusion SUA is associated with the development of lupus nephritis in patients with normal kidney function also SUA in-dependently correlated with disease activity and chronicity in LN.


2018 ◽  
Author(s):  
Tim Dierckx ◽  
Sylvie Goletti ◽  
Laurent Chiche ◽  
Laurent Daniel ◽  
Bernard Lauwerys ◽  
...  

Objective: Glycoprotein acetylation (GlycA) is a novel biomarker for chronic inflammation, associated to cardiovascular risk. Serum GlycA levels are increased in several inflammatory diseases, including systemic lupus erythematosus (SLE). We investigated the relevance of serum GlycA measurement in SLE and lupus nephritis (LN). Methods: GlycA was measured by NMR in 194 serum samples from patients and controls. Comparisons were performed between groups. Clinical and biological parameters were tested for correlation with GlycA levels. The predictive value of GlycA to differentiate proliferative from non-proliferative LN was determined using logistic regression models. Results: GlycA was correlated to C-reactive protein (CRP), neutrophil count, proteinuria and the SLE disease activity index (SLEDAI), and inversely with serum albumin. GlycA was higher in active (n=105) than in quiescent (n=39) SLE patients, in healthy controls (n=29), and in patients with non-lupus nephritis (n=21), despite a more altered renal function in the latter. In patients with biopsy-proven active LN, GlycA was higher in proliferative (n=32) than non-proliferative (n=11) LN, independent of renal function and proteinuria level. Logistic regression models showed that, in univariate models, GlycA outperforms traditional biomarkers. A bivariate model using GlycA and BMI better predicted the proliferative status of LN than a model comprising CRP, renal function (eGFR), serum albumin, proteinuria, C3 consumption and the presence of anti-dsDNA antibodies. Conclusion: Serum GlycA is elevated in SLE, and correlates with disease activity and LN. Serum GlycA, which summarizes different inflammatory processes, could be a valuable biomarker to discriminate proliferative from non-proliferative LN and should be tested in large, prospective cohorts.


2020 ◽  
Author(s):  
Yi Yang ◽  
Ran Luo ◽  
Yichun Cheng ◽  
Tingting Liu ◽  
Wei Dai ◽  
...  

Abstract Background Increased leucine-rich α2-glycoprotein-1 (LRG1) has been observed in various inflammatory and autoimmune diseases. We aimed to explore the expression and role of LRG1 in lupus nephritis (LN). Methods Plasma LRG1 (pLRG1) was measured by enzyme-linked immunosorbent assay in 101 patients with renal biopsy-proven LN and 21 healthy controls (HC). Relationships between pLRG1 and clinical and pathological characteristics were analyzed. The expression of LRG1 in peripheral blood leukocytes and kidney was detected by flow cytometry, immunohistochemistry and immunofluorescence, respectively. Further cell experiments were focused on the role of LRG1. Results We found that LRG1 was expressed in plasma, some peripheral blood leukocytes, proximal tubule and several inflammatory cells. The levels of LRG1 in plasma, peripheral blood leukocytes and kidney were elevated in LN patients as compared to HC. Plasma expression levels of LRG1 correlated positively with renal function and renal disease activity, and reflect specific pathologic lesions in the kidneys of patients with LN. Interleukin-1β and interleukin-6, not tumor necrosis factor-α and interferon γ induced the LRG1 expression in human renal tubular epithelial cell line. Moreover, stimulation of recombinant human LRG1 could inhibit late apoptosis, promote proliferation and regulate expression of inflammatory factors and cytokines. Conclusions Plasma expression levels of LRG1 were associated with renal function, disease activity, and pathology in LN. It might also be involved in renal inflammation, proliferation and apoptosis of endothelial cells. LRG1 might be a potential prognosis novel predictor in LN patients.


2020 ◽  
Author(s):  
Yi Yang ◽  
Ran Luo ◽  
Yichun Cheng ◽  
Tingting Liu ◽  
Wei Dai ◽  
...  

Abstract Background Increased leucine-rich α2-glycoprotein-1 (LRG1) has been observed in various inflammatory and autoimmune diseases. We aimed to explore the expression and role of LRG1 in lupus nephritis (LN). Methods Plasma LRG1 (pLRG1) was measured by enzyme-linked immunosorbent assay in 101 patients with renal biopsy-proven LN and 21 healthy controls (HC). Relationships between pLRG1 and clinical and pathological characteristics were analyzed. The expression of LRG1 in peripheral blood leukocytes and kidney was detected by flow cytometry, immunohistochemistry and immunofluorescence, respectively. Further cell experiments were focused on the role of LRG1. Results We found that LRG1 was expressed in plasma, some peripheral blood leukocytes, proximal tubule and several inflammatory cells. The levels of LRG1 in plasma, peripheral blood leukocytes and kidney were elevated in LN patients as compared to HC. Plasma expression levels of LRG1 correlated positively with renal function and renal disease activity, and reflect specific pathologic lesions in the kidneys of patients with LN. Interleukin-1β and interleukin-6, not tumor necrosis factor-α and interferon γ induced the LRG1 expression in human renal tubular epithelial cell line. Moreover, stimulation of recombinant human LRG1 could inhibit late apoptosis, promote proliferation and regulate expression of inflammatory factors and cytokines. Conclusions Plasma expression levels of LRG1 were associated with renal function, disease activity, and pathology in LN. It might also be involved in renal inflammation, proliferation and apoptosis of endothelial cells. LRG1 might be a potential prognosis novel predictor in LN patients.


2019 ◽  
Author(s):  
Yi Yang ◽  
Ran Luo ◽  
Yichun Cheng ◽  
Tingting Liu ◽  
Wei Dai ◽  
...  

Abstract Background Increased leucine-rich α2-glycoprotein-1 (LRG1) has been observed in various inflammatory and autoimmune diseases. We aimed to explore the expression and role of LRG1 in lupus nephritis (LN).Methods Plasma LRG1 (pLRG1) was measured by enzyme-linked immunosorbent assay in 101 patients with renal biopsy-proven LN and 21 healthy controls (HC). Relationships between pLRG1 and clinical and pathological characteristics were analyzed. The expression of LRG1 in peripheral blood leukocytes and kidney was detected by flow cytometry, immunohistochemistry and immunofluorescence, respectively. Further cell experiments were focused on the role of LRG1.Results We found that LRG1 was expressed in plasma, some peripheral blood leukocytes, proximal tubule and several inflammatory cells. The levels of LRG1 in plasma, peripheral blood leukocytes and kidney were elevated in LN patients as compared to HC. Plasma expression levels of LRG1 correlated positively with renal function and renal disease activity, and reflect specific pathologic lesions in the kidneys of patients with LN. Interleukin-1β and interleukin-6, not tumor necrosis factor-α and interferon γ induced the LRG1 expression in human renal tubular epithelial cell line. Moreover, stimulation of recombinant human LRG1 could inhibit late apoptosis, promote proliferation and regulate expression of inflammatory factors and cytokines.Conclusions Plasma expression levels of LRG1 were associated with renal function, disease activity, and pathology in LN. It might also be involved in renal inflammation, proliferation and apoptosis of endothelial cells. LRG1 might be a potential prognosis novel predictor in LN patients.


2018 ◽  
Vol 15 (1) ◽  
pp. 2-6 ◽  
Author(s):  
Chi Chiu Mok

The Treat-to-Target (T2T) principle has been advocated in a number of inflammatory and non-inflammatory medical illnesses. Tight control of disease activity has been shown to improve the outcome of rheumatoid arthritis and psoriatic arthritis as compared to the conventional approach. However, whether T2T can be applied to patients with lupus nephritis is still under emerging discussion. Treatment of lupus nephritis should target at inducing and maintaining remission of the kidney inflammation so as to preserve renal function and improve survival in the longterm. However, there is no universal agreement on the definition of remission or low disease activity state of nephritis, as well as the time points for switching of therapies. Moreover, despite the availability of objective parameters for monitoring such as proteinuria and urinary sediments, differentiation between ongoing activity and damage in some patients with persistent urinary abnormalities remains difficult without a renal biopsy. A large number of serum and urinary biomarkers have been tested in lupus nephritis but none of them have been validated for routine clinical use. In real life practice, therapeutic options for lupus nephritis are limited. As patients with lupus nephritis are more prone to infective complications, tight disease control with aggressive immunosuppressive therapies may have safety concern. Not until the feasibility, efficacy, safety and cost-effectiveness of T2T in lupus nephritis is confirmed by comparative trials, this approach should not be routinely recommended with the current treatment armamentarium and monitoring regimes.


Lupus ◽  
2016 ◽  
Vol 25 (11) ◽  
pp. 1230-1236 ◽  
Author(s):  
R Gupta ◽  
A Aggarwal ◽  
S Sinha ◽  
L Rajasekhar ◽  
A Yadav ◽  
...  

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1403.2-1403
Author(s):  
L. Bohmat ◽  
N. Shevchenko ◽  
I. Bessonova

Background:Lupus nephritis is the most severe and adverse systemic lupus erythematosus (SLE) syndrome. According to modern recommendations, the clinical manifestations of active nephritis should be taken under medical control in 6 months after the start of the disease’s treatment1.Objectives:The aim of this study was to examine the functional status of the kidneys in children with SLE in the course of the disease for more than one year.Methods:The analysis included case histories of 43 patients with SLE, mostly females (41), aged 7 to 18 years (mean age 14.4 years) with disease duration of 4.75 ± 0.58 years of whom 22 were less than three years, 21 - more than three years. All children received corticosteroid therapy, at the time of the examination the average dose was 13.85 ± 1.86 mg per day in terms of prednisolone. The second component of therapy was azathioprine (average dose 97.61 ± 2.11 mg). All children received hydroxychloroquine (5 mg/kg per day).To determine the functional state of the kidneys a clinical analysis of urine, a study of the scope of specific gravity of urine during the day (Zymnytsky test), the content of creatinine and urea in serum to determine the glomerular filtration rate (GFR), the level of microalbuminuria per day were evaluated.Results:Renal involvement in the developed SLE occurred in 73.08% of patients. Among them, therapy during the first 6 months was considered quite effective in 58.06% of patients. It was found that in children with disease duration from one to three years proteinuria was registered in 68.18%, a decrease in GFR in 4.45% and hyperfiltration in 9.09%. In the group of children with duration of SLE more than three years revealed deeper changes in renal function; there was proteinuria in 90.47%, the frequency of GFR decreased was in 19.04%, a decrease of renal concentration function was in 14.28% of cases.Indicators of renal function in children with SLE depending on the duration of the disease (M ± m)IndicatorDuration of the diseasefrom 1 year to 3 years n = 22over 3 yearsn = 21Creatinine, mmol/l0,080 ± 0,0140,090 ± 0,018Мочевина, mmol/l5,66 ± 1,425,63 ± 1,61GFR, ml/min117,05 ± 19,68100,20 ± 18,98 *Microalbuminuria, mg/day24,41 ± 13,1334,73 ± 24,76Density min1,007 ± 0,0051,006 ± 0,005Density max1,024 ± 0,0051,019 ± 0,005 ***р<0,03;**р<0,01 the probability of differences when comparing between groupsConclusion:Long-term follow-up of children with SLE over one year reveals a prolongation of renal dysfunction, which worsens after three years, and is the basis for the development of irreversible renal impairment.References:[1]European evidence-based recommendations for the diagnosis and treatment of childhood-onset lupus nephritis: the SHARE initiative /Noortje Groot, Nienke de Graeff, Stephen D Marks et all. //Ann Rheum Dis. 2017 Dec;76(12):1965-1973.Disclosure of Interests:None declared


Sign in / Sign up

Export Citation Format

Share Document