Chronicity index, especially glomerular sclerosis, is the most powerful predictor of renal response following immunosuppressive treatment in patients with lupus nephritis

2018 ◽  
Vol 21 (2) ◽  
pp. 458-467 ◽  
Author(s):  
Dong-Jin Park ◽  
Sung-Eun Choi ◽  
Haimuzi Xu ◽  
Ji-Hyoun Kang ◽  
Kyung-Eun Lee ◽  
...  
Keyword(s):  
Lupus Nephritis ◽  
Immunosuppressive Treatment ◽  
Glomerular Sclerosis ◽  
Powerful Predictor ◽  
Renal Response ◽  
Chronicity Index

scholarly journals P0266PREDICTIVE FACTORS OF COMPLETE RENAL RESPONSE IN PROLIFERATIVE LUPUS NEPHRITIS: A COLLABORATIVE STUDY

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Beatriz Sanchez Alamo ◽  
Clara Maria Cases Corona ◽  
Serena Gatius ◽  
Patricia Dominguez Torres ◽  
Elena Valdes ◽  
...  
Keyword(s):  
Logistic Regression ◽  
Lupus Nephritis ◽  
Kidney Biopsy ◽  
Univariate Analysis ◽  
Immunosuppressive Treatment ◽  
Collaborative Study ◽  
Class Iii ◽  
Renal Response ◽  
Proliferative Lupus Nephritis

Abstract Background and Aims Proliferative lupus nephritis (class III and IV) is the most severe form of lupus nephritis and requires prompt diagnosis and treatment with immunosuppressive therapy. Since it represents the most serious entity and has the greatest functional consequences there is a need to determine which factors in proliferative lupus nephritis are most predictive of good long-term renal function. Method Methods We analysed the data of 49 biopsy-proven proliferative lupus nephritis (18,4% class III and 81,6% class IV) of three different Spanish hospitals to find prognostic factors for complete renal response (CRR), defined as loss of <25% of eGFR and the absence of proteinuria and microhematuria at the end of the follow up. Sociodemographic, clinical, laboratory, and treatment-related data at the time of kidney biopsy and during follow-up were obtained. We performed univariate analysis and logistic regression to identify independent risk factors. Results The median follow-up was 8 years (IQR: 3-12,5), during which time 18 patients (36,7 %) achieved CRR. In the univariate analysis complete renal response was related to: (1) at the diagnosis to: age [40,52 (11,29) years vs 29,92 (11,93) p=0,004]; (2) in kidney biopsy to less leukocyte infiltration (42,3% p=0,05); (3) during the follow up to: less comorbities (27,8% vs 64,3% p=0,02), less infections (27,8% vs 58,6% p=0,04) and less hospitalizations due to infections (0% vs 33,3% p=0,010), less prevalence of high BP (22,2% vs 60,7% p=0,01), (4) at the end of follow up to : serum albumin [3,97 (0,59) vs 4,31(0,19) mg/dL p=0,03]. In the logistic regression comorbidies (HR : 5,71 95%IC: 1,56-20,93 p=0,008) and age at the moment of diagnosis (HR : 1,046 95%IC:1,001-1,071 p=0,04) were related to complete renal response. We didn´t find any differences concerning treatments. Conclusion Proliferative lupus nephritis is one of the most severe manifestations of lupus nephritis, resulting in increased morbidity and mortality. Traditionally it has been thought that older patients have a worst prognosis, however we demonstrated that they achieved more frequently CRR. In the management of the patients traditional reno protective measures like strict control of BP must be considered since it is a predictive factor of CRR. We shouldn´t forget about the implications of an aggressive immunosuppressive treatment such as hospitalizations due to infections and comorbities.

scholarly journals Beyond ISN/RPS lupus nephritis classification: adding chronicity index to clinical variables predicts kidney survival

Kidney360 ◽  
2021 ◽  
pp. 10.34067/KID.0005512021
Author(s):  
Gabriella Moroni ◽  
Giulia Porata ◽  
Francesca Raffiotta ◽  
Silvana Quaglini ◽  
Giulia Frontini ◽  
...  
Keyword(s):  
Lupus Nephritis ◽  
Serum Creatinine ◽  
Arterial Hypertension ◽  
Kidney Function ◽  
Kidney Biopsy ◽  
Activity Index ◽  
Cox Model ◽  
Glomerular Sclerosis ◽  
Histological Features ◽  
Chronicity Index

Background. A renewed interest for activity and chronicity indices as predictors of lupus nephritis (LN) outcome has emerged. Revised National Institutes of Health (NIH) activity and chronicity indices have been proposed to classify LN lesions but should be validated by future studies. Aims of this study: i) to detect the histological features associated with the development of Kidney Function Impairment (KFI); ii) to identify the best clinical-histological model to predict KFI at time of kidney biopsy. Methods. LN patients with kidney biopsy containing >10 glomeruli per specimen were admitted to the study. Univariate and multivariate logistic regression and Cox proportional hazards model were used to investigate whether activity and chronicity indices could predict KFI development. Results. Among 203 LN participants followed for 14 years, correlations were found between activity index and its components and clinical-laboratory signs of active LN at baseline. Chronicity index was correlated with serum creatinine. Thus, serum creatinine was significantly and directly correlated with both activity and chronicity indexes. At multivariate analysis glomerular sclerosis (OR:3.0478, CI:1.173-7.91, P=0.022) and fibrous crescents (OR:6.8352, CI:3.218-14.519, P<0.001) associated with either moderate/severe tubular atrophy (OR:3.1697, CI:1.042-9.643, P=0.0421), or with interstitial fibrosis (OR:2.361, CI:1.047-5.322, P=0.0383) predicted KFI. Considering both clinical and histological features, serum creatinine (OR:1.677; 1.311-2.145; P<0.001), arterial hypertension (OR:4.641, CI: 1.902-11.324, P<0.001), glomerular sclerosis (OR:2.123, CI:1.001-4.503, P=0.049), and fibrous crescents (OR:5.182, CI: 2.433-11.037, P<0.001) independently predicted KFI. Older age (P<0.001) and longer delay between clinical onset of LN and kidney biopsy (P<0.001) were significantly correlated with baseline chronicity index. Conclusions. Chronicity index and its components, but not activity index, were significantly associated with an impairment of kidney function. The Cox model showed that serum creatinine, arterial hypertension, chronic glomerular lesions and delay in kidney biopsy predicted KFI. These data reinforce the importance of timely kidney biopsy in LN.

Non-albumin proteinuria in lupus nephritis with tubulointerstitial inflammation and its clinical significance

QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
Ashraf Mahmoud Okba ◽  
Nehal Elfawy Mahmoud ◽  
Mariam Maged Amin ◽  
Mariam Ahmed Mohamed Mamdouh
Keyword(s):  
Lupus Nephritis ◽  
Immunosuppressive Treatment ◽  
Prognostic Significance ◽  
Systemic Lupus Erythematosis ◽  
Creatinine Ratio ◽  
Systemic Lupus ◽  
Renal Response ◽  
Case Series Study ◽  
Before And After ◽  
Tubulointerstitial Inflammation

Abstract Background Tubulointerstitial inflammation (TI) associated with systemic lupus erythematosis is an increasing finding in lupus nephritis. TI severity may have prognostic significance in the renal outcomes of lupus nephritis. Here, we aimed to determine whether non-albumin proteinuria is associated with TI severity and with the renal response in lupus nephritis. Objective To investigate the possible association between non-albumin proteinuria, tubulointerstial inflammation severity and poor renal response after immunosuppressive treatment. Patients and Methods This is a case series study which was conducted on 100 patients with systemic lupus erythematosis recruited from the outpatient clinic of Clinical Immunology at Ain Shams University Hospitals. Subject ages were between 13-53 years old, each one was subjected to detailed history, physical examination, laboratory investigations including serum creatinine before and after treatment, protein/creatinine ratio before and after treatment, albumin/creatinine ratio, ESR, CRP, CBC, C3 C4, anti DNA, eGFR and renal biopsy Results Our results showed that non-albumin proteinuria (uPCR − uACR) was significantly higher in patients with moderate-to-severe TI than in patients with no-tomild TI. Further, higher uPCR − uACR levels at baseline were associated with poor renal response after 6 months of treatment. Conclusion we found that non-albumin proteinuria (uPCR-uACR) is associated with severe tubulointerstitial inflammation (TI) in lupus nephritis.

scholarly journals Immunosuppressive Treatment for Lupus Nephritis: Long-Term Results in 178 Patients

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Elena V. Zakharova ◽  
Tatiana A. Makarova ◽  
Elena V. Zvonova ◽  
Alina M. Anilina ◽  
Ekaterina S. Stolyarevich
Keyword(s):  
Lupus Nephritis ◽  
Lupus Erythematosus ◽  
Patient Survival ◽  
Immunosuppressive Treatment ◽  
Long Term Results ◽  
Renal Response ◽  
Severe Systemic Lupus Erythematosus ◽  
Damage Accrual ◽  
Definition Of

Lupus nephritis is one of the most severe Systemic Lupus Erythematosus features, defining treatment modality and prognosis. Our retrospective study, including 178 patients treated for lupus nephritis during 23 years with mostly cyclophosphamide-based initial regimens followed by azathioprine or mycophenolic acid, demonstrates 84.8% of renal response with 19.2% of flares, 15-year patient survival 78.7% and kidney survival 76.3%, and low damage accrual. Both patient and kidney survival significantly differ for subgroups that achieved complete or partial renal response and nonresponders: patient 15-year survival 95% versus 65% versus 35%; kidney 15-year survival 100% versus 58% versus 0%, respectively. 51% (24 out of 47) of patients evaluated at the end of the study period sustained complete renal response; however, only 9 of them had 0 disease activity according to SELENA SLEDAI scale, while 13 patients had scores 2–4 due to the serological abnormalities only. We conclude that (1) initial treatment with cyclophosphamide followed by azathioprine is effective and can be used in agreement with International Guidelines until the evidence for biological treatments benefits becomes available; (2) complete and even partial renal response have positive prognostic value, and failure to achieve renal response negatively influences kidney and patient survival; (3) the validity of complete renal response in SLE is questioned by the absence of conventional definition of SLE remission.

scholarly journals Hsa_circ_0123190 acts as a competitive endogenous RNA to regulate APLNR expression by sponging hsa-miR-483-3p in lupus nephritis

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Chunyi Zhang ◽  
Congcong Gao ◽  
Xueqi Di ◽  
Siwan Cui ◽  
Wenfang Liang ◽  
...  
Keyword(s):  
Lupus Nephritis ◽  
Lupus Erythematosus ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β1 ◽  
Luciferase Reporter Assay ◽  
Luciferase Reporter ◽  
Circular Rnas ◽  
Reporter Assay ◽  
Clinical Value ◽  
Chronicity Index

Abstract Background Lupus nephritis (LN) is one of the most severe complications of systemic lupus erythematosus (SLE). Circular RNAs (circRNAs) can act as competitive endogenous RNAs (ceRNAs) to regulate gene transcription, which is involved in mechanism of many diseases. However, the role of circRNA in lupus nephritis has been rarely reported. In this study, we aim to investigate the clinical value of circRNAs and explore the mechanism of circRNA involvement in the pathogenesis of LN. Methods Renal tissues from three untreated LN patients and three normal controls (NCs) were used to identify differently expressed circRNAs by next-generation sequencing (NGS). Validated assays were used by quantitative reverse transcription polymerase chain reaction (qRT-PCR). The interactions between circRNA and miRNA, or miRNA and mRNA were further determined by luciferase reporter assay. The extent of renal fibrosis between the two groups was assessed by Masson-trichome staining and immunohistochemistry (IHC) staining. Results 159 circRNAs were significantly dysregulated in LN patients compared with NCs. The expression of hsa_circ_0123190 was significantly decreased in the renal tissues of patients with LN (P = 0.014). Bio-informatics analysis and luciferase reporter assay illustrated that hsa_circ_0123190 can act as a sponge for hsa-miR-483-3p, which was also validated to interact with APLNR. APLNR mRNA expression was related with chronicity index (CI) of LN (P = 0.033, R2 = 0.452). Moreover, the fibrotic-related protein, transforming growth factor-β1 (TGF-β1), which was regulated by APLNR, was more pronounced in the LN group (P = 0.018). Conclusion Hsa_circ_0123190 may function as a ceRNA to regulate APLNR expression by sponging hsa-miR-483-3p in LN.

scholarly journals FRI0181 ORGAN DAMAGE FREE SURVIVAL IN SOUTHERN CHINESE PATIENTS WITH ACTIVE LUPUS NEPHRITIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 674.1-674
Author(s):  
C. C. Mok ◽  
C. S. Sin ◽  
K. C. Hau ◽  
T. H. Kwan
Keyword(s):  
Lupus Nephritis ◽  
Regression Model ◽  
Cox Regression ◽  
Organ Damage ◽  
Renal Survival ◽  
Cox Regression Model ◽  
Free Survival ◽  
Renal Response

Background:The goals of treatment of lupus nephritis (LN) are to induce remission, retard the progression of chronic kidney disease, prevent organ complications and ultimately reduce mortality. Previous cohort studies of LN have mainly focused on the risk of mortality and development of end stage renal failure (ESRF) (renal survival). The cumulative frequency of LN patients who survive without organ damage, which correlates better with the balance between treatment efficacy and toxicity, as well as quality of life, has not been well studied.Objectives:To study the organ damage free survival and its predictive factors in patients with active LN.Methods:Consecutive patients who fulfilled ≥4 ACR/SLICC criteria for SLE and with biopsy proven active LN between 2003 and 2018 were retrospectivey analyzed. Those with organ damage before LN onset were excluded. Data on renal parameters and treatment regimens were collected. Complete renal response (CR) was defined as normalization of serum creatinine (SCr), urine P/Cr (uPCR) <0.5 and inactive urinary sediments. Partial renal response (PR) was defined as ≥50% reduction in uPCR and <25% increase in SCr. Organ damage of SLE was assessed by the ACR/SLICC damage index (SDI). The cumulative risk of having any organ damage or mortality since LN was studied by Kaplan-Meier’s analysis. Factors associated with a poor outcome were studied by a forward stepwise Cox regression model, with entry of covariates with p<0.05 and removal with p>0.10.Results:273 LN patients were identified but 64 were excluded (organ damage before LN onset). 211 LN patients were studied (92% women; age at SLE 30.4±13.5 years; SLE duration at LN 1.9±3.1years). 47 (22%) patients had nephrotic syndrome and 60 (29%) were hypertensive. Histological LN classes was: III/IV±V (75.1%), I/II (7.8%) and pure V (17.1%) (histologic activity and chronicity score 7.0±4.2 and 1.8±1.5, respectively). Induction regimens were: prednisolone (33.1±17.5mg/day) in combination with intravenous cyclophosphamide (CYC) (21.4%; 1.0±0.2g per pulse), oral CYC (8.6%; 96.4±37.8mg/day), azathioprine (AZA) (14.3%; 78.6±25.2mg/day), mycophenolate mofetil (MMF) (22.8%; 1.9±0.43g/day) and tacrolimus (TAC) (17.1%; 4.3±1.1mg/day). After a follow-up of 8.6±5.4 years, 94(45%) patient developed organ damage (SDI≥1) and 21(10%) patients died. The commonest organ damage was renal (36.3%) and musculoskeletal (17.9%), and the causes of death were: infection (38.1%), malignancy (19.0%), cardiovascular events (9.5%) and ESRF complications (9.5%). At last visit, 114 (55%) patients survived without any organ damage. The cumulative organ damage free survival at 5, 10 and 15 years after renal biopsy was 73.5%, 59.6% and 48.3%, respectively. The 5, 10 and 15-year renal survival rate were 95.2%, 92.0% and 84.1% respectively. In a Cox regression model, nephritic relapse (HR 3.72[1.78-7.77]), proteinuric relapse (HR 2.30[1.07-4.95]) and older age (HR 1.89[1.05-3.37]) were associated with either organ damage or mortality, whereas CR (HR 0.25[0.12-0.50]) at month 12 were associated with organ damage free survival. Baseline SCr, uPCR and histological LN classes were not significantly associated with a poor outcome. Among patients with class III/IV LN, the long-term organ damage free survival were not significantly different in users of MMF (reference) from CYC (IV/oral) (HR 1.45[0.76- 2.75]) or TAC (HR 1.03[0.26-1.62]) as induction therapy.Conclusion:Organ damage free survival is achieved in 55% of patients with active LN upon 9 years of follow-up. CYC/MMF/TAC based induction regimens did not differ for the long-term outcome of LN. Targeting complete renal response and preventing renal relapses remain important goals of LN treatment.Acknowledgments:NILDisclosure of Interests:None declared

Combined immunosuppressive treatment (CIST) in lupus nephritis: a multicenter, randomized controlled study

2018 ◽  
Vol 38 (4) ◽  
pp. 1047-1054 ◽  
Author(s):  
Yuan An ◽  
Yunshan Zhou ◽  
Liqi Bi ◽  
Bo Liu ◽  
Hong Wang ◽  
...  
Keyword(s):  
Lupus Nephritis ◽  
Immunosuppressive Treatment ◽  
Randomized Controlled Study ◽  
Controlled Study ◽  
Randomized Controlled

scholarly journals P0429OUTCOMES OF LUPUS NEPHRITIS OVER AN ERA OF EVOLVING IMMUNOSUPPRESSION

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Jason McMinn ◽  
Colin C Geddes ◽  
Emily McQuarrie
Keyword(s):  
Lupus Nephritis ◽  
Electronic Patient Record ◽  
Immunosuppressive Treatment ◽  
Complete Response ◽  
Histopathological Diagnosis ◽  
Class V ◽  
Remission Rates ◽  
Induction Regimen ◽  
Before And After

Abstract Background and Aims The reported incidence of lupus nephritis (LN) is approximately 6.1 cases per million population per year in Scotland based on Scottish Renal Registry biopsy data. Despite immunosuppressive treatment, approximately 10-30% of patients will progress to established renal failure (ERF) within 15 years. In December 2007, our unit moved from a protocol of Cyclophosphamide/ steroid induction with Azathioprine/ Prednisolone maintenance to Mycophenolate/ steroid induction and maintenance. We undertook this study to compare remission rates before and after this change. Method A retrospective electronic patient record analysis was performed for all patients in our centre with a documented native renal biopsy showing a histopathological diagnosis of LN, between 1 July 1993 and 31 December 2017. Repeat biopsies were excluded. Baseline demographics, histopathological class and first and second line induction and maintenance therapies were recorded. Endpoints analysed were; partial and complete response (as defined in KDIGO Clinical Practice Guideline for Glomerulonephritis 2012), time to achieve this response, relapse, progression to ERF and death. Results 120 patients who underwent a biopsy during the 24.5-year period received a diagnosis of lupus nephritis. 82.5% of patients were Caucasian. Median duration of follow-up was 72 months. 15% of patients died and 5% developed ERF within the follow-up period, representing one death per 56 patient years and one incident case of ERF per 168 patient years. There were 40 patients in the pre-December 2007 group and 80 in the post-December 2007 group. Those in the earlier group were younger, with a mean age of 35.4 years versus 44.8 years in the later group (p=0.002). 23% had class V in the earlier group compared to 15% in the later group (p=0.31). Proportions of female patients were 80% and 75% in the early and late groups respectively (p=0.54). Median creatinine was 106µmol/L in the pre-December 2007 group and 89.5 µmol/L in the post-December 2007 group (p=0.96). Patients in the pre- and post- December 2007 groups had comparable rates of complete response, at 72% and 71% respectively. However, those diagnosed before December 2007 were slower to respond, with a median time to achieve complete response of 10.5 months, compared to 6 months in those diagnosed after 1 December 2007 (p=0.007). Conclusion Following a change in our immunosuppressive induction regimen from Cyclophosphamide/ steroids to Mycophenolate/ steroids, our response rates have remained similar, however speed of attaining remission has improved.

Sign in / Sign up

Export Citation Format

Share Document