scholarly journals Change of Renal Gallium Uptake Correlated with Change of Inflammation Activity in Renal Pathology in Lupus Nephritis Patients

2021 ◽  
Vol 10 (20) ◽  
pp. 4654
Author(s):  
Tsu-Yi Hsieh ◽  
Yi-Ching Lin ◽  
Wei-Ting Hung ◽  
Yi-Ming Chen ◽  
Mei-Chin Wen ◽  
...  
Keyword(s):  
Lupus Nephritis ◽  
Lupus Erythematosus ◽  
Activity Index ◽  
Left Kidney ◽  
Renal Pathology ◽  
Class Iii ◽  
Stage Renal Disease ◽  
End Stage ◽  
Active Inflammation ◽  
Histological Results

Background: Lupus nephritis (LN) often lead to end-stage renal disease in systemic lupus erythematosus patients. This study aimed to investigate the clinical application of renal gallium-67 scans for determining renal histological parameters in LN patients. Methods: Between 2006 and 2018, 237 biopsy-proven and 35 repeat biopsies LN patients who underwent renal gallium scans before or after biopsy were included for analysis. The classification and scoring of LN were assessed according to the International Society of Nephrology/Renal Pathology Society. A delayed 48-h gallium scan was performed and interpreted by semiquantitative methods using left kidney/spine (K/S) ratio. The renal histological results were compared with gallium uptake. Results: Out of 237 participants, 180 (76%) had proliferative LN. Baseline gallium left K/S ratio was significantly higher in class IV LN as compared to class III (median (interquartile range, IQR): 1.16 (1.0–1.3), 0.95 (0.9–1.1), respectively, p < 0.001). Furthermore, changes in gallium uptake between two biopsies were positively correlated with changes activity index (r = 0.357, p = 0.035), endocapillary hypercellularity (r = 0.385, p = 0.032), and neutrophils infiltration (r = 0.390, p = 0.030) in renal pathology. Conclusions: Renal gallium uptake is associated with active inflammation in LN. Changes in renal gallium uptake positively correlated with changes in activity index in renal pathology.

Tacrolimus versus cyclophosphamide as treatment for diffuse proliferative or membranous lupus nephritis: a non-randomized prospective cohort study

Lupus ◽  
2012 ◽  
Vol 21 (9) ◽  
pp. 1025-1035 ◽  
Author(s):  
S Wang ◽  
X Li ◽  
L Qu ◽  
R Wang ◽  
Y Chen ◽  
...  
Keyword(s):  
Lupus Nephritis ◽  
Renal Disease ◽  
Lupus Erythematosus ◽  
Activity Index ◽  
Disease Activity Index ◽  
Severe Adverse Effect ◽  
Open Label ◽  
Severe Renal Disease ◽  
Stage Renal Disease ◽  
End Stage

Treatment of lupus nephritis (LN) with cyclophosphamide (CYC) is effective but retains a certain severe adverse effect. Tacrolimus (TAC) may be a suitable treatment for LN. Forty patients with diffuse proliferative or membranous LN were recruited for this non-randomized open-label study — 67.5% (27/40) had nephrotic proteinuria (>3.5 g/day) and 50.0% (20/40) had low estimated glomerular filtration rate (eGFR) (<60 mL/min/1.73m2). We compared the efficacy and adverse effects of TAC (0.04–0.08 mg/kg/d)/prednisone for 12 months (TAC group, n = 20) with intravenous CYC (750 mg/m2 per month)/prednisone for six months followed by azathioprine (Aza) (100 mg/day)/prednisone for six months (CYC group, n = 20). The TAC target concentration was 6–8 ng/mL or 4–6 ng/mL, respectively, when induction or maintenance therapy was required and 4.0 ng/mL for patient with renal insufficiency. In the TAC group, mean urinary protein excretion decreased significantly from 5.00 ± 1.91 g/day at baseline to 2.54 ± 1.68 g/day after two weeks of therapy ( P < 0.001), compared with the CYC group (4.9 ± 19.4 g/day), P = 0.001, and 65.0% (13/20) achieved partial remission at one month, compared with the CYC group (0/20), P < 0.001. The incidence of complete remission (CR) was significantly higher in the TAC group than in the CYC group (55.0% vs.15.0% by five months, P = 0.008, and 75.0% vs.40.0% by 12 months, P = 0.025, respectively). The significant improvement in serum anti-dsDNA and systemic lupus erythematosus (SLE) disease activity index (DAI) was in the TAC group relative to the CYC group at 12 months ( P = 0.031, P = 0.003, respectively). The eGFR improved in the TAC group from 59.90 ± 23.64 mL/min/1.73m2 at baseline to 93.75 ± 28.52 mL/min/1.73m2 after 12 months, P = 0.001. In the CYC group, two patients developed end-stage renal disease (ESRD), three patients experienced serious pneumonia, and one patient died. Our preliminary study showed TAC is a safe and effective treatment for LN with severe renal disease, and with less-severe adverse events compared with CYC followed Aza therapy. Further larger sample studies are needed to confirm our conclusion.

scholarly journals A lupus nephritis kezelésének irányelvei, valamint a mycofenolat mofetil hatékonyságának bemutatása intézetünk lupus nephritises betegeinek körében

2016 ◽  
Vol 157 (35) ◽  
pp. 1385-1393
Author(s):  
Melinda Zsuzsanna Szabó ◽  
Emese Kiss
Keyword(s):  
Lupus Nephritis ◽  
Lupus Erythematosus ◽  
End Stage Renal Disease ◽  
Remission Induction ◽  
Class Iii ◽  
Systemic Lupus ◽  
Single Centre ◽  
Life Threatening ◽  
Stage Renal Disease ◽  
End Stage

The authors present the latest guideline for the treatment of lupus nephritis and their own single-centre results with mycofenolate mofetil treated lupus nephritis. Lupus nephritis and mainly its proliferative form is a frequent and potentially life-threatening manifestation of systemic lupus erythematosus that can lead to end-stage renal disease. The treatment of lupus nephritis greatly improved in the last decades; mycofenolate mofetil has become an alternative of cyclophosphamide both in remission induction and as a maintenance regimen as well in the treatment of Class III and IV glomerulonephritis. The authors ordered mycofenolate mofetil for 25 patients with lupus nephritis so far. Histologically most of them had Class III (A/C) or IV (A) glomerulonephritis (30–30%), and only 16% of the patients had renal impairment at that time. Mycofenolate mofetil given after glucocorticoid and cyclophosphamide induction therapy reduced the daily proteinuria from 3.18 grs to 1.06 grs. Complete remission could be achieved in 24% and partial remission in 48% of the patients. The authors conclude that mycofenolate mofetil is effective in the therapy of lupus nephritis. Orv. Hetil., 2016, 157(35), 1385–1393.

Interleukin-34 as a marker for subclinical proliferative lupus nephritis

Lupus ◽  
2020 ◽  
Vol 29 (6) ◽  
pp. 607-616
Author(s):  
Asmaa SM Abdel-Rehim ◽  
Nesrine A Mohamed ◽  
Marwa M Shakweer
Keyword(s):  
Lupus Nephritis ◽  
Lupus Erythematosus ◽  
Activity Index ◽  
Renal Involvement ◽  
Clinical Manifestations ◽  
Surrogate Marker ◽  
Disease Activity Index ◽  
Class Iii ◽  
Group I ◽  
Dsdna Antibodies

Background Lupus nephritis (LN) is an ominous manifestation of systemic lupus erythematosus (SLE). Clinical renal affection is present in about 70% of lupus patients, and more patients have histological evidence of renal involvement without clinical manifestations. This study aimed to investigate the potential role of serum interleukin-34 (IL-34) as an early marker for the detection of silent LN. Methods Thirty-three lupus patients with silent LN (group I), 37 patients with clinical LN (group II) and 20 controls were included. The SLE Disease Activity Index (SLEDAI), IL-34, anti-dsDNA antibodies and renal biopsy were assessed in all patients. Results Serum IL-34 levels were significantly higher in all lupus patients compared to healthy controls ( p < 0.001) and showed a significant positive correlation with SLEDAI score. SLE patients with positive anti-dsDNA antibodies had more active disease according to SLEDAI and higher levels of IL-34 than those with negative anti-dsDNA antibodies. In both studied groups, serum IL-34 levels were significantly higher in patients with proliferative LN (class III and class IV) than those with non-proliferative lupus (class II and class V) and controls. Yet, in both groups, IL-34 was not useful in differentiating active from chronic renal affection. Conclusion In lupus patients with insignificant proteinuria, serum levels of IL-34 distinguished the different histological classes of subclinical LN. Serum IL-34 may be used as a surrogate marker for early renal affection in silent LN, especially the proliferative type.

Frequency of Class III and IV Nephritis in Systemic Lupus Erythematosus Without Clinical Renal Involvement: An Analysis of Predictive Measures

2011 ◽  
Vol 39 (1) ◽  
pp. 79-85 ◽  
Author(s):  
DAISUKE WAKASUGI ◽  
TAKAHISA GONO ◽  
YASUSHI KAWAGUCHI ◽  
MASAKO HARA ◽  
YUMI KOSEKI ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Nephritis ◽  
Lupus Erythematosus ◽  
High Titer ◽  
Renal Involvement ◽  
Renal Pathology ◽  
Class Iii ◽  
Systemic Lupus ◽  
Clinically Normal ◽  
Dsdna Antibody

Objective.To determine the frequency of International Society of Nephrology/Renal Pathology Society (ISN/RPS) class III or IV lupus nephritis in patients with systemic lupus erythematosus (SLE) without clinical renal involvement.Methods.We investigated the renal pathology of 195 patients with SLE, including 86 patients without clinical renal involvement.Results.Lupus nephritis other than class I was found in 58% of the patients without clinical renal involvement, and class III and IV nephritis was found in 15% of these patients. To reveal the predictive measures involved in class III or IV lupus nephritis, we explored the clinical measures in patients with SLE who did not have clinical renal involvement. Anti-dsDNA antibody titers were significantly higher (p = 0.0266) and C3 values were significantly lower (p = 0.0073) in patients with class III or IV lupus nephritis than in patients without class III or IV lupus nephritis. The sensitivity and specificity values were 77% and 73%, respectively, for cutoff levels of both 40 IU/ml for anti-dsDNA antibodies and 55 mg/dl for C3 (OR 8.8, p = 0.0011).Conclusion.The frequency of nephritis, including ISN/RPS class III and IV, was unexpectedly high in SLE patients without clinical renal involvement. ISN/RPS class III or IV lupus nephritis could be hidden in patients with SLE who present both a high titer of anti-dsDNA antibody and a low concentration of C3, even when they have clinically normal urinary findings and renal function.

scholarly journals The ISN/RPS 2016 classification predicts renal prognosis in patients with first-onset class III/IV lupus nephritis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Asaka Hachiya ◽  
Munetoshi Karasawa ◽  
Takahiro Imaizumi ◽  
Noritoshi Kato ◽  
Takayuki Katsuno ◽  
...  
Keyword(s):  
Complete Remission ◽  
Lupus Nephritis ◽  
Clinical Outcomes ◽  
Lupus Erythematosus ◽  
Cox Regression ◽  
Interstitial Fibrosis ◽  
Activity Index ◽  
Class Iii ◽  
Cox Regression Analysis ◽  
First Onset

AbstractLupus nephritis (LN) is a life-threatening complication of systemic lupus erythematosus. The 2003 pathological classification of LN was revised in 2016; it quantitatively evaluates the interstitium in addition to the glomeruli. We performed a retrospective multi-centre cohort study and investigated the utility of the 2016 classification—including the activity index (AI), chronicity index (CI), and each pathological component to predict complete remission or renal function decline, defined as 1.5-fold increase in serum creatinine levels—and compare with that of the 2003 classification. Ninety-one consecutive adult patients with first-onset class III/IV LN who were newly prescribed any immunosuppressants were enrolled and followed up for a median of 51 months from January 2004. Cox regression analysis demonstrated the subclasses based on the 2003 classification, which mainly evaluate glomerular lesions, were not associated with clinical outcomes. After adjustments for estimated glomerular filtration rate and urinary protein levels, higher CI and higher interstitial fibrosis and lower hyaline deposit scores were associated with renal functional decline. Similarly, higher CI and interstitial inflammation scores were associated with failure to achieve complete remission. Therefore, the 2016 classification can predict the clinical outcomes more precisely than the 2003 classification.

scholarly journals Baseline HDAC6 and TFF3 proteins overexpression as prognostic markers of lupus nephritis relapse

2020 ◽  
Vol 9 (2) ◽  
pp. e14-e14
Author(s):  
Eman Hassan Abdelbary ◽  
Noha Farouk Ahmed ◽  
Adel Abdelmohsen Ghorab
Keyword(s):  
Lupus Nephritis ◽  
Serum Creatinine ◽  
Lupus Erythematosus ◽  
Kidney Diseases ◽  
Activity Index ◽  
Kidney Injury ◽  
Class Iii ◽  
Clinicopathologic Characteristics ◽  
Chronicity Index

Introduction: Lupus nephritis (LN) is a substantial manifestation of systemic lupus erythematosus (SLE). HDAC6 is overexpressed in various kidney diseases, and its inhibition slows kidney injury progression. Urinary TFF3 increases in chronic kidney diseases (CKDs) and may be associated with patient’s outcome. Objectives: This study aimed to examine the relationship between renal HDAC6 and TFF3 proteins expression and with clinicopathologic characteristics and outcome of LN. Patients and Methods: HDAC6 and TFF3 proteins’ expression was immunohistochemically detected in 56 cases of LN. They were correlated to patients’ age, gender, urinary 24 hours protein and serum creatinine levels at baseline and during follow up. Additionally, they were correlated to LN classes, activity index (AI) and chronicity index (CI) and relapse free survival (RFS). Results: HDAC6 overexpression was significantly associated with serum creatinine and 24 hours proteinuria levels at baseline (P = 0.041 and P =0.026 respectively) and during follow up (P < 0.001). It was associated with AI and CI of class III and IV LN (P = 0.047 and 0.003 respectively). TFF3 overexpression was associated with higher serum creatinine and more proteinuria at baseline (P = 0.015 and 0.001 respectively) and during follow up (P < 0.001). It was significantly associated with higher CI (P = 0.001). Both markers were associated with shorter RFS (P < 0.001). Conclusion: HDAC6 and TFF3 proteins are associated with clinicopathologic features of renal damage in LN. They are reliable predictors of patients’ RFS, which makes them good candidates for risk stratification of patients and targeted therapy.

Histological predictors of renal outcome in lupus nephritis: the importance of tubulointerstitial lesions and scoring of glomerular lesions

Lupus ◽  
2018 ◽  
Vol 27 (9) ◽  
pp. 1455-1463 ◽  
Author(s):  
B Obrișcă ◽  
R Jurubiță ◽  
A Andronesi ◽  
B Sorohan ◽  
C Achim ◽  
...  
Keyword(s):  
Lupus Nephritis ◽  
Lupus Erythematosus ◽  
Kidney Biopsy ◽  
Renal Outcome ◽  
Predictors Of Outcome ◽  
End Point ◽  
Tubulointerstitial Lesions ◽  
Cox Proportional Hazard Regression ◽  
Stage Renal Disease ◽  
End Stage

Introduction Lupus nephritis (LN) affects nearly 60% of patients with systemic lupus erythematosus and up to 30% of them will progress to end-stage renal disease (ESRD), despite receiving aggressive immunosuppressive therapy. The prognostic value of ISN/RPS classification is controversial. Therefore, we aimed to identify clinical and pathological predictors of outcome in LN patients independent of this classification. Material and methods Thirty-seven patients with LN who underwent percutaneous kidney biopsy between 1997 and 2016 were included in this study. Twenty clinical and twenty histological variables were tested for their association with a composite end-point of doubling of serum creatinine, ESRD and death. Univariate and multivariate Cox proportional hazard regression analysis were performed to identify independent predictors of outcome. Results During a median follow-up period of 48 months (IQR: 17.5–120 months), 21.6% of patients reached the composite end-point. The overall survival rate of our cohort was 89% at one year, 86% at five years, 74% at 10 years and 64% at 20 years. Patients with Class IV LN showed the worst prognosis with 44% survival at 10 years, while those who additionally showed crescents and global sclerosis on kidney biopsy had an even lower survival of 21% and 0% at 10 years, respectively. After multivariate adjustment, we identified estimated glomerular filtration rate at baseline (HR, 0.91 per ml/min /1.73 m2; 95% CI, 0.84 to 0.99), 24-hour proteinuria at baseline (HR, 2.04 per g/d; 95% CI, 1.19 to 3.5), crescents (HR, 1.068 per %; 95% CI, 1.003 to 1.091), global sclerosis (HR, 1.036 per %; 95% CI, 0.984 to 1.091), presence of adhesions (HR, 9.2; 95% CI, 1.38 to 61.2) and tubulitis (HR, 13.1; 95% CI; 1.3 to 131) as independent predictors of outcome in our cohort of LN. Conclusions Our study identified glomerular (crescents, global sclerosis, adhesions) and tubulointerstitial (tubulitis) lesions, in addition to clinical variables (renal function, 24-hour proteinuria), as important predictors of renal outcome, independent of the ISN/RPS classification. We suggest that the ISN/RPS classification could be improved by a quantitative assessment of glomeruli with active and chronic lesions and by a greater emphasis given to tubulointerstitial lesions.

scholarly journals Association of Intrarenal B-Cell Infiltrates with Clinical Outcome in Lupus Nephritis: A Study of 192 Cases

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Yan Shen ◽  
Chuan-Yin Sun ◽  
Feng-Xia Wu ◽  
Yi Chen ◽  
Min Dai ◽  
...  
Keyword(s):  
B Cells ◽  
Lupus Nephritis ◽  
B Cell ◽  
Lupus Erythematosus ◽  
Kidney Diseases ◽  
Activity Index ◽  
Disease Activity Index ◽  
Immunological Responses ◽  
Renal Biopsies ◽  
Stage Renal Disease

Background. Lupus nephritis (LN) remains a major cause of morbidity and end-stage renal disease. Dysfunction of B lymphocytes is thought to be important in the pathogenesis of SLE/LN. Intrarenal B cells have been found in several forms of inflammatory kidney diseases although their role in LN renal is not well defined.Methods. Intrarenal B cells were analyzed in 192 renal biopsies from patients diagnosed with lupus nephritis. Immunohistochemical staining of serial sections was performed for each LN patient using CD20, CD3, and CD21 antibodies.Results. Intrarenal B cells were more likely to be associated with class IV LN and were mainly distributed in the renal interstitium, with very few in the glomerulus. The systemic lupus erythematosus disease activity index (SLEDAI), blood urea nitrogen, and serum creatinine levels were all significantly greater in the LN-B cell groups (allP<0.05). LN renal activity and chronicity indices correlated with B-cells infiltrates (allP<0.0001). Renal biopsies were classified into four distinct categories according to the organizational grade of inflammatory cell infiltrates. Germinal center- (GC-) like structures were not identified in any LN biopsies.Conclusion. It is hypothesized that intrarenal B cells enhance immunological responses and exaggerate the local immune response to persisting autoimmune damage in the tubulointerstitium.

scholarly journals Punicalagin Ameliorates Lupus Nephritis via Inhibition of PAR2

2020 ◽  
Vol 21 (14) ◽  
pp. 4975
Author(s):  
Yohan Seo ◽  
Chin Hee Mun ◽  
So-Hyeon Park ◽  
Dongkyu Jeon ◽  
Su Jeong Kim ◽  
...  
Keyword(s):  
Lupus Nephritis ◽  
Cell Line ◽  
Lupus Erythematosus ◽  
High Throughput Screening ◽  
Intraperitoneal Administration ◽  
Kidney Injury ◽  
High Rate ◽  
Beneficial Effects ◽  
Stage Renal Disease ◽  
End Stage

Lupus nephritis (LN) is the most frequent phenotype in patients with systemic lupus erythematosus (SLE) and has a high rate of progression to end-stage renal disease, in spite of intensive treatment and maintenance therapies. Recent evidence suggests that protease-activated receptor-2 (PAR2) is a therapeutic target for glomerulonephritis. In this study, we performed a cell-based high-throughput screening and identified a novel potent PAR2 antagonist, punicalagin (PCG, a major polyphenol enriched in pomegranate), and evaluated the effects of PCG on LN. The effect of PCG on PAR2 inhibition was observed in the human podocyte cell line and its effect on LN was evaluated in NZB/W F1 mice. In the human podocyte cell line, PCG potently inhibited PAR2 (IC50 = 1.5 ± 0.03 µM) and significantly reduced the PAR2-mediated activation of ERK1/2 and NF-κB signaling pathway. In addition, PCG significantly decreased PAR2-induced increases in ICAM-1 and VCAM-1 as well as in IL-8, IFN-γ, and TNF-α expression. Notably, the intraperitoneal administration of PCG significantly alleviated kidney injury and splenomegaly and reduced proteinuria and renal ICAM-1 and VCAM-1 expression in NZB/W F1 mice. Our results suggest that PCG has beneficial effects on LN via inhibition of PAR2, and PCG is a potential therapeutic agent for LN.

scholarly journals Systemic lupus erythematosus, lupus nephritis and end-stage renal disease: a pragmatic review mapping disease severity and progression

Lupus ◽  
2020 ◽  
Vol 29 (9) ◽  
pp. 1011-1020
Author(s):  
Anadi Mahajan ◽  
Justyna Amelio ◽  
Kerry Gairy ◽  
Gavneet Kaur ◽  
Roger A Levy ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Nephritis ◽  
Renal Disease ◽  
Lupus Erythematosus ◽  
End Stage Renal Disease ◽  
Elevated Serum ◽  
Systemic Lupus ◽  
Histological Transformation ◽  
Stage Renal Disease ◽  
End Stage

Objective The understanding of systemic lupus erythematosus (SLE) and lupus nephritis (LN) pathogenesis remains incomplete. This review assessed LN development in SLE, within-LN progression and progression to end-stage renal disease (ESRD). Methods A keyword-based literature search was conducted, and 26 publications were included. Results Overall, 7–31% of patients had LN at SLE diagnosis; 31–48% developed LN after SLE diagnosis, most within 5 years. Class IV was the most commonly found LN class and had the worst prognosis. Histological transformation occurred in 40–76% of patients, more frequently from non-proliferative rather than proliferative lesions. Cumulative 5- and 10-year ESRD incidences in patients with SLE were 3% and 4%, respectively, and 3–11% and 6–19%, respectively, in patients with SLE and LN. Conclusions Elevated serum creatinine was identified as a predictor of worsening disease state, and progression within LN classes and from SLE/LN to ESRD. This review highlights the substantial risk for developing LN and progressing to ESRD amongst patients with SLE.

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